Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease
Identifieur interne : 000A52 ( Main/Corpus ); précédent : 000A51; suivant : 000A53Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease
Auteurs : Anthony E. Lang ; Steven Gill ; Nik K. Patel ; Andres Lozano ; John G. Nutt ; Richard Penn ; David J. Brooks ; Gary Hotton ; Elena Moro ; Peter Heywood ; Matthew A. Brodsky ; Kim Burchiel ; Patrick Kelly ; Arif Dalvi ; Burton Scott ; Mark Stacy ; Dennis Turner ; V. G. Frederich Wooten ; William J. Elias ; Edward R. Laws ; Vijay Dhawan ; A. Jon Stoessl ; James Matcham ; Robert J. Coffey ; Michael TraubSource :
- Annals of Neurology [ 0364-5134 ] ; 2006-03.
Abstract
Objective: Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open‐label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Methods: Thirty‐four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15μg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and 18F‐dopa uptake. Results: At 6 months, mean percentage changes in “off” UPDRS motor score were −10.0% and −4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, −23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean 18F‐dopa influx constant (p = 0.019) was observed. Serious, device‐related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on‐study and two in the open‐label extension). Interpretation: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F‐dopa uptake. It is uncertain whether technical differences between this trial and positive open‐label studies contributed in any way this negative outcome. Ann Neurol 2006
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DOI: 10.1002/ana.20737
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease</title><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><affiliation><mods:affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Gill, Steven" sort="Gill, Steven" uniqKey="Gill S" first="Steven" last="Gill">Steven Gill</name><affiliation><mods:affiliation>Frenchay Hospital, Bristol, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Patel, Nik K" sort="Patel, Nik K" uniqKey="Patel N" first="Nik K." last="Patel">Nik K. 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Laws</name><affiliation><mods:affiliation>University of Virginia, Charlottesville, VA</mods:affiliation></affiliation></author><author><name sortKey="Dhawan, Vijay" sort="Dhawan, Vijay" uniqKey="Dhawan V" first="Vijay" last="Dhawan">Vijay Dhawan</name><affiliation><mods:affiliation>North Shore Long Island Jewish Research Institute, Manhasset, NY</mods:affiliation></affiliation></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name><affiliation><mods:affiliation>University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation></author><author><name sortKey="Matcham, James" sort="Matcham, James" uniqKey="Matcham J" first="James" last="Matcham">James Matcham</name><affiliation><mods:affiliation>Amgen Ltd., Cambridge, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Coffey, Robert J" sort="Coffey, Robert J" uniqKey="Coffey R" first="Robert J." last="Coffey">Robert J. Coffey</name><affiliation><mods:affiliation>Medtronic Inc., Minneapolis, MN</mods:affiliation></affiliation></author><author><name sortKey="Traub, Michael" sort="Traub, Michael" uniqKey="Traub M" first="Michael" last="Traub">Michael Traub</name><affiliation><mods:affiliation>Amgen Inc., Thousand Oaks, CA</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:6CFE15E0209DCA843C277139795F853D5A1C135C</idno><date when="2006" year="2006">2006</date><idno type="doi">10.1002/ana.20737</idno><idno type="url">https://api.istex.fr/document/6CFE15E0209DCA843C277139795F853D5A1C135C/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000A52</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease</title><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><affiliation><mods:affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Gill, Steven" sort="Gill, Steven" uniqKey="Gill S" first="Steven" last="Gill">Steven Gill</name><affiliation><mods:affiliation>Frenchay Hospital, Bristol, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Patel, Nik K" sort="Patel, Nik K" uniqKey="Patel N" first="Nik K." last="Patel">Nik K. Patel</name><affiliation><mods:affiliation>Frenchay Hospital, Bristol, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Lozano, Andres" sort="Lozano, Andres" uniqKey="Lozano A" first="Andres" last="Lozano">Andres Lozano</name><affiliation><mods:affiliation>Toronto Western Research Institute, Toronto, Canada</mods:affiliation></affiliation></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G." last="Nutt">John G. Nutt</name><affiliation><mods:affiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</mods:affiliation></affiliation></author><author><name sortKey="Penn, Richard" sort="Penn, Richard" uniqKey="Penn R" first="Richard" last="Penn">Richard Penn</name><affiliation><mods:affiliation>University of Chicago, Chicago, IL</mods:affiliation></affiliation></author><author><name sortKey="Brooks, David J" sort="Brooks, David J" uniqKey="Brooks D" first="David J." last="Brooks">David J. Brooks</name><affiliation><mods:affiliation>Imperial College, Hammersmith Hospital, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Hotton, Gary" sort="Hotton, Gary" uniqKey="Hotton G" first="Gary" last="Hotton">Gary Hotton</name><affiliation><mods:affiliation>Imperial College, Hammersmith Hospital, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Moro, Elena" sort="Moro, Elena" uniqKey="Moro E" first="Elena" last="Moro">Elena Moro</name><affiliation><mods:affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Heywood, Peter" sort="Heywood, Peter" uniqKey="Heywood P" first="Peter" last="Heywood">Peter Heywood</name><affiliation><mods:affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Brodsky, Matthew A" sort="Brodsky, Matthew A" uniqKey="Brodsky M" first="Matthew A." last="Brodsky">Matthew A. Brodsky</name><affiliation><mods:affiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</mods:affiliation></affiliation></author><author><name sortKey="Burchiel, Kim" sort="Burchiel, Kim" uniqKey="Burchiel K" first="Kim" last="Burchiel">Kim Burchiel</name><affiliation><mods:affiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</mods:affiliation></affiliation></author><author><name sortKey="Kelly, Patrick" sort="Kelly, Patrick" uniqKey="Kelly P" first="Patrick" last="Kelly">Patrick Kelly</name><affiliation><mods:affiliation>New York University Medical Center, New York, NY</mods:affiliation></affiliation></author><author><name sortKey="Dalvi, Arif" sort="Dalvi, Arif" uniqKey="Dalvi A" first="Arif" last="Dalvi">Arif Dalvi</name><affiliation><mods:affiliation>University of Chicago, Chicago, IL</mods:affiliation></affiliation></author><author><name sortKey="Scott, Burton" sort="Scott, Burton" uniqKey="Scott B" first="Burton" last="Scott">Burton Scott</name><affiliation><mods:affiliation>Duke Movement Disorders Clinic, Durham, NC</mods:affiliation></affiliation></author><author><name sortKey="Stacy, Mark" sort="Stacy, Mark" uniqKey="Stacy M" first="Mark" last="Stacy">Mark Stacy</name><affiliation><mods:affiliation>Duke University, Durham, NC</mods:affiliation></affiliation></author><author><name sortKey="Turner, Dennis" sort="Turner, Dennis" uniqKey="Turner D" first="Dennis" last="Turner">Dennis Turner</name><affiliation><mods:affiliation>Duke University, Durham, NC</mods:affiliation></affiliation></author><author><name sortKey="Wooten, V G Frederich" sort="Wooten, V G Frederich" uniqKey="Wooten V" first="V. G. Frederich" last="Wooten">V. G. Frederich Wooten</name><affiliation><mods:affiliation>University of Virginia, Charlottesville, VA</mods:affiliation></affiliation></author><author><name sortKey="Elias, William J" sort="Elias, William J" uniqKey="Elias W" first="William J." last="Elias">William J. Elias</name><affiliation><mods:affiliation>University of Virginia, Charlottesville, VA</mods:affiliation></affiliation></author><author><name sortKey="Laws, Edward R" sort="Laws, Edward R" uniqKey="Laws E" first="Edward R." last="Laws">Edward R. Laws</name><affiliation><mods:affiliation>University of Virginia, Charlottesville, VA</mods:affiliation></affiliation></author><author><name sortKey="Dhawan, Vijay" sort="Dhawan, Vijay" uniqKey="Dhawan V" first="Vijay" last="Dhawan">Vijay Dhawan</name><affiliation><mods:affiliation>North Shore Long Island Jewish Research Institute, Manhasset, NY</mods:affiliation></affiliation></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name><affiliation><mods:affiliation>University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation></author><author><name sortKey="Matcham, James" sort="Matcham, James" uniqKey="Matcham J" first="James" last="Matcham">James Matcham</name><affiliation><mods:affiliation>Amgen Ltd., Cambridge, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Coffey, Robert J" sort="Coffey, Robert J" uniqKey="Coffey R" first="Robert J." last="Coffey">Robert J. Coffey</name><affiliation><mods:affiliation>Medtronic Inc., Minneapolis, MN</mods:affiliation></affiliation></author><author><name sortKey="Traub, Michael" sort="Traub, Michael" uniqKey="Traub M" first="Michael" last="Traub">Michael Traub</name><affiliation><mods:affiliation>Amgen Inc., Thousand Oaks, CA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2006-03">2006-03</date><biblScope unit="volume">59</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="459">459</biblScope><biblScope unit="page" to="466">466</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">6CFE15E0209DCA843C277139795F853D5A1C135C</idno><idno type="DOI">10.1002/ana.20737</idno><idno type="ArticleID">ANA20737</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective: Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open‐label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Methods: Thirty‐four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15μg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and 18F‐dopa uptake. Results: At 6 months, mean percentage changes in “off” UPDRS motor score were −10.0% and −4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, −23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean 18F‐dopa influx constant (p = 0.019) was observed. Serious, device‐related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on‐study and two in the open‐label extension). Interpretation: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F‐dopa uptake. It is uncertain whether technical differences between this trial and positive open‐label studies contributed in any way this negative outcome. Ann Neurol 2006</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Anthony E. Lang MD</name><affiliations><json:string>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>Steven Gill MD</name><affiliations><json:string>Frenchay Hospital, Bristol, United Kingdom</json:string></affiliations></json:item><json:item><name>Nik K. Patel MD</name><affiliations><json:string>Frenchay Hospital, Bristol, United Kingdom</json:string></affiliations></json:item><json:item><name>Andres Lozano MD</name><affiliations><json:string>Toronto Western Research Institute, Toronto, Canada</json:string></affiliations></json:item><json:item><name>John G. Nutt MD</name><affiliations><json:string>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</json:string></affiliations></json:item><json:item><name>Richard Penn MD</name><affiliations><json:string>University of Chicago, Chicago, IL</json:string></affiliations></json:item><json:item><name>David J. Brooks MD</name><affiliations><json:string>Imperial College, Hammersmith Hospital, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Gary Hotton MD</name><affiliations><json:string>Imperial College, Hammersmith Hospital, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Elena Moro MD</name><affiliations><json:string>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>Peter Heywood MD</name><affiliations><json:string>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>Matthew A. Brodsky MD</name><affiliations><json:string>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</json:string></affiliations></json:item><json:item><name>Kim Burchiel MD</name><affiliations><json:string>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</json:string></affiliations></json:item><json:item><name>Patrick Kelly MD</name><affiliations><json:string>New York University Medical Center, New York, NY</json:string></affiliations></json:item><json:item><name>Arif Dalvi MD</name><affiliations><json:string>University of Chicago, Chicago, IL</json:string></affiliations></json:item><json:item><name>Burton Scott MD</name><affiliations><json:string>Duke Movement Disorders Clinic, Durham, NC</json:string></affiliations></json:item><json:item><name>Mark Stacy MD</name><affiliations><json:string>Duke University, Durham, NC</json:string></affiliations></json:item><json:item><name>Dennis Turner MD</name><affiliations><json:string>Duke University, Durham, NC</json:string></affiliations></json:item><json:item><name>V. G. Frederich Wooten MD</name><affiliations><json:string>University of Virginia, Charlottesville, VA</json:string></affiliations></json:item><json:item><name>William J. Elias MD</name><affiliations><json:string>University of Virginia, Charlottesville, VA</json:string></affiliations></json:item><json:item><name>Edward R. Laws MD</name><affiliations><json:string>University of Virginia, Charlottesville, VA</json:string></affiliations></json:item><json:item><name>Vijay Dhawan PhD</name><affiliations><json:string>North Shore Long Island Jewish Research Institute, Manhasset, NY</json:string></affiliations></json:item><json:item><name>A. Jon Stoessl MD</name><affiliations><json:string>University of British Columbia, Vancouver, British Columbia, Canada</json:string></affiliations></json:item><json:item><name>James Matcham</name><affiliations><json:string>Amgen Ltd., Cambridge, United Kingdom</json:string></affiliations></json:item><json:item><name>Robert J. Coffey MD</name><affiliations><json:string>Medtronic Inc., Minneapolis, MN</json:string></affiliations></json:item><json:item><name>Michael Traub MD</name><affiliations><json:string>Amgen Inc., Thousand Oaks, CA</json:string></affiliations></json:item></author><articleId><json:string>ANA20737</json:string></articleId><language><json:string>eng</json:string></language><abstract>Objective: Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open‐label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Methods: Thirty‐four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15μg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and 18F‐dopa uptake. Results: At 6 months, mean percentage changes in “off” UPDRS motor score were −10.0% and −4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, −23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean 18F‐dopa influx constant (p = 0.019) was observed. Serious, device‐related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on‐study and two in the open‐label extension). Interpretation: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F‐dopa uptake. It is uncertain whether technical differences between this trial and positive open‐label studies contributed in any way this negative outcome. Ann Neurol 2006</abstract><qualityIndicators><score>7.42</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 783 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1717</abstractCharCount><pdfWordCount>4516</pdfWordCount><pdfCharCount>29737</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>242</abstractWordCount></qualityIndicators><title>Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease</title><genre><json:string>article</json:string></genre><host><volume>59</volume><publisherId><json:string>ANA</json:string></publisherId><pages><total>8</total><last>466</last><first>459</first></pages><issn><json:string>0364-5134</json:string></issn><issue>3</issue><subject><json:item><value>Original 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uri="https://api.istex.fr/document/6CFE15E0209DCA843C277139795F853D5A1C135C/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2006</date></publicationStmt><notesStmt><note>Amgen Inc.</note><note>Medtronic, Inc.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease</title><author><persName><forename type="first">Anthony E.</forename><surname>Lang</surname></persName><roleName type="degree">MD</roleName><note type="correspondence"><p>Correspondence: Department of Medicine (Neurology), University of Toronto, Toronto Western Hospital Movement Disorders Center, 399 Bathurst Street, 7McL, Toronto, ON, Canada M5T 2S8</p></note><affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</affiliation></author><author><persName><forename type="first">Steven</forename><surname>Gill</surname></persName><roleName type="degree">MD</roleName><affiliation>Frenchay Hospital, Bristol, United Kingdom</affiliation></author><author><persName><forename type="first">Nik K.</forename><surname>Patel</surname></persName><roleName type="degree">MD</roleName><affiliation>Frenchay Hospital, Bristol, United Kingdom</affiliation></author><author><persName><forename type="first">Andres</forename><surname>Lozano</surname></persName><roleName type="degree">MD</roleName><affiliation>Toronto Western Research Institute, Toronto, Canada</affiliation></author><author><persName><forename type="first">John G.</forename><surname>Nutt</surname></persName><roleName type="degree">MD</roleName><affiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</affiliation></author><author><persName><forename type="first">Richard</forename><surname>Penn</surname></persName><roleName type="degree">MD</roleName><affiliation>University of Chicago, Chicago, IL</affiliation></author><author><persName><forename type="first">David J.</forename><surname>Brooks</surname></persName><roleName type="degree">MD</roleName><affiliation>Imperial College, Hammersmith Hospital, London, United Kingdom</affiliation></author><author><persName><forename type="first">Gary</forename><surname>Hotton</surname></persName><roleName type="degree">MD</roleName><affiliation>Imperial College, Hammersmith Hospital, London, United Kingdom</affiliation></author><author><persName><forename type="first">Elena</forename><surname>Moro</surname></persName><roleName type="degree">MD</roleName><affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</affiliation></author><author><persName><forename type="first">Peter</forename><surname>Heywood</surname></persName><roleName type="degree">MD</roleName><affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</affiliation></author><author><persName><forename type="first">Matthew A.</forename><surname>Brodsky</surname></persName><roleName type="degree">MD</roleName><affiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</affiliation></author><author><persName><forename type="first">Kim</forename><surname>Burchiel</surname></persName><roleName type="degree">MD</roleName><affiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</affiliation></author><author><persName><forename type="first">Patrick</forename><surname>Kelly</surname></persName><roleName type="degree">MD</roleName><affiliation>New York University Medical Center, New York, NY</affiliation></author><author><persName><forename type="first">Arif</forename><surname>Dalvi</surname></persName><roleName type="degree">MD</roleName><affiliation>University of Chicago, Chicago, IL</affiliation></author><author><persName><forename type="first">Burton</forename><surname>Scott</surname></persName><roleName type="degree">MD</roleName><affiliation>Duke Movement Disorders Clinic, Durham, NC</affiliation></author><author><persName><forename type="first">Mark</forename><surname>Stacy</surname></persName><roleName type="degree">MD</roleName><affiliation>Duke University, Durham, NC</affiliation></author><author><persName><forename type="first">Dennis</forename><surname>Turner</surname></persName><roleName type="degree">MD</roleName><affiliation>Duke University, Durham, NC</affiliation></author><author><persName><forename type="first">V. G. Frederich</forename><surname>Wooten</surname></persName><roleName type="degree">MD</roleName><affiliation>University of Virginia, Charlottesville, VA</affiliation></author><author><persName><forename type="first">William J.</forename><surname>Elias</surname></persName><roleName type="degree">MD</roleName><affiliation>University of Virginia, Charlottesville, VA</affiliation></author><author><persName><forename type="first">Edward R.</forename><surname>Laws</surname></persName><roleName type="degree">MD</roleName><affiliation>University of Virginia, Charlottesville, VA</affiliation></author><author><persName><forename type="first">Vijay</forename><surname>Dhawan</surname></persName><roleName type="degree">PhD</roleName><affiliation>North Shore Long Island Jewish Research Institute, Manhasset, NY</affiliation></author><author><persName><forename type="first">A. Jon</forename><surname>Stoessl</surname></persName><roleName type="degree">MD</roleName><affiliation>University of British Columbia, Vancouver, British Columbia, Canada</affiliation></author><author><persName><forename type="first">James</forename><surname>Matcham</surname></persName><affiliation>Amgen Ltd., Cambridge, United Kingdom</affiliation></author><author><persName><forename type="first">Robert J.</forename><surname>Coffey</surname></persName><roleName type="degree">MD</roleName><affiliation>Medtronic Inc., Minneapolis, MN</affiliation></author><author><persName><forename type="first">Michael</forename><surname>Traub</surname></persName><roleName type="degree">MD</roleName><affiliation>Amgen Inc., Thousand Oaks, CA</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2006-03"></date><biblScope unit="volume">59</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="459">459</biblScope><biblScope unit="page" to="466">466</biblScope></imprint></monogr><idno type="istex">6CFE15E0209DCA843C277139795F853D5A1C135C</idno><idno type="DOI">10.1002/ana.20737</idno><idno type="ArticleID">ANA20737</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2006</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Objective: Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open‐label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Methods: Thirty‐four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15μg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and 18F‐dopa uptake. Results: At 6 months, mean percentage changes in “off” UPDRS motor score were −10.0% and −4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, −23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean 18F‐dopa influx constant (p = 0.019) was observed. Serious, device‐related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on‐study and two in the open‐label extension). Interpretation: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F‐dopa uptake. It is uncertain whether technical differences between this trial and positive open‐label studies contributed in any way this negative outcome. 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creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Anthony E.</givenNames><familyName>Lang</familyName><degrees>MD</degrees></personName><contactDetails><email>lang@uhnres.utoronto.ca</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Steven</givenNames><familyName>Gill</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Nik K.</givenNames><familyName>Patel</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Andres</givenNames><familyName>Lozano</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af4"><personName><givenNames>John G.</givenNames><familyName>Nutt</familyName><degrees>MD</degrees></personName></creator><creator 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Jon</givenNames><familyName>Stoessl</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au23" creatorRole="author" affiliationRef="#af13"><personName><givenNames>James</givenNames><familyName>Matcham</familyName></personName></creator><creator xml:id="au24" creatorRole="author" affiliationRef="#af14"><personName><givenNames>Robert J.</givenNames><familyName>Coffey</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au25" creatorRole="author" affiliationRef="#af15"><personName><givenNames>Michael</givenNames><familyName>Traub</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="CA" type="organization"><unparsedAffiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="GB" type="organization"><unparsedAffiliation>Frenchay Hospital, Bristol, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="CA" type="organization"><unparsedAffiliation>Toronto Western Research Institute, Toronto, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>University of Chicago, Chicago, IL</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="GB" type="organization"><unparsedAffiliation>Imperial College, Hammersmith Hospital, London, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="US" type="organization"><unparsedAffiliation>New York University Medical Center, New York, NY</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="US" type="organization"><unparsedAffiliation>Duke Movement Disorders Clinic, Durham, NC</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="US" type="organization"><unparsedAffiliation>Duke University, Durham, NC</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="US" type="organization"><unparsedAffiliation>University of Virginia, Charlottesville, VA</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="US" type="organization"><unparsedAffiliation>North Shore Long Island Jewish Research Institute, Manhasset, NY</unparsedAffiliation></affiliation><affiliation xml:id="af12" countryCode="CA" type="organization"><unparsedAffiliation>University of British Columbia, Vancouver, British Columbia, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af13" countryCode="GB" type="organization"><unparsedAffiliation>Amgen Ltd., Cambridge, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af14" countryCode="US" type="organization"><unparsedAffiliation>Medtronic Inc., Minneapolis, MN</unparsedAffiliation></affiliation><affiliation xml:id="af15" countryCode="US" type="organization"><unparsedAffiliation>Amgen Inc., Thousand Oaks, CA</unparsedAffiliation></affiliation></affiliationGroup><fundingInfo><fundingAgency>Amgen Inc.</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Medtronic, Inc.</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><section xml:id="abs1-1"><title type="main"><span cssStyle="text-decoration:underline"><i>Objective</i></span></title><p>Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open‐label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin).</p></section><section xml:id="abs1-2"><title type="main"><span cssStyle="text-decoration:underline"><i>Methods</i></span></title><p>Thirty‐four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15μg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and <sup>18</sup>F‐dopa uptake.</p></section><section xml:id="abs1-3"><title type="main"><span cssStyle="text-decoration:underline"><i>Results</i></span></title><p>At 6 months, mean percentage changes in “off” UPDRS motor score were −10.0% and −4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, −23.0 to 12.0, <i>p</i> = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean <sup>18</sup>F‐dopa influx constant (<i>p</i> = 0.019) was observed. Serious, device‐related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on‐study and two in the open‐label extension).</p></section><section xml:id="abs1-4"><title type="main"><span cssStyle="text-decoration:underline"><i>Interpretation</i></span></title><p>Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased <sup>18</sup>F‐dopa uptake. It is uncertain whether technical differences between this trial and positive open‐label studies contributed in any way this negative outcome. Ann Neurol 2006</p></section></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Intraputamenal GDNF in PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Randomized controlled trial of intraputamenal glial cell line–derived neurotrophic factor infusion in Parkinson disease</title></titleInfo><name type="personal"><namePart type="given">Anthony E.</namePart><namePart type="family">Lang</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</affiliation><description>Correspondence: Department of Medicine (Neurology), University of Toronto, Toronto Western Hospital Movement Disorders Center, 399 Bathurst Street, 7McL, Toronto, ON, Canada M5T 2S8</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Steven</namePart><namePart type="family">Gill</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Frenchay Hospital, Bristol, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nik K.</namePart><namePart type="family">Patel</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Frenchay Hospital, Bristol, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andres</namePart><namePart type="family">Lozano</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Toronto Western Research Institute, Toronto, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John G.</namePart><namePart type="family">Nutt</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Richard</namePart><namePart type="family">Penn</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University of Chicago, Chicago, IL</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David J.</namePart><namePart type="family">Brooks</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Imperial College, Hammersmith Hospital, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gary</namePart><namePart type="family">Hotton</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Imperial College, Hammersmith Hospital, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elena</namePart><namePart type="family">Moro</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Heywood</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Matthew A.</namePart><namePart type="family">Brodsky</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kim</namePart><namePart type="family">Burchiel</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Oregon Health and Science University, Parkinson Center of Oregon, Portland, OR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrick</namePart><namePart type="family">Kelly</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>New York University Medical Center, New York, NY</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Arif</namePart><namePart type="family">Dalvi</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University of Chicago, Chicago, IL</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Burton</namePart><namePart type="family">Scott</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Duke Movement Disorders Clinic, Durham, NC</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mark</namePart><namePart type="family">Stacy</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Duke University, Durham, NC</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dennis</namePart><namePart type="family">Turner</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Duke University, Durham, NC</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">V. G. Frederich</namePart><namePart type="family">Wooten</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University of Virginia, Charlottesville, VA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">William J.</namePart><namePart type="family">Elias</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University of Virginia, Charlottesville, VA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Edward R.</namePart><namePart type="family">Laws</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University of Virginia, Charlottesville, VA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vijay</namePart><namePart type="family">Dhawan</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>North Shore Long Island Jewish Research Institute, Manhasset, NY</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A. Jon</namePart><namePart type="family">Stoessl</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University of British Columbia, Vancouver, British Columbia, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">James</namePart><namePart type="family">Matcham</namePart><affiliation>Amgen Ltd., Cambridge, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robert J.</namePart><namePart type="family">Coffey</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Medtronic Inc., Minneapolis, MN</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael</namePart><namePart type="family">Traub</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Amgen Inc., Thousand Oaks, CA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2006-03</dateIssued><dateCaptured encoding="w3cdtf">2005-08-01</dateCaptured><dateValid encoding="w3cdtf">2005-10-06</dateValid><copyrightDate encoding="w3cdtf">2006</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">3</extent><extent unit="references">16</extent><extent unit="words">5364</extent></physicalDescription><abstract lang="en">Objective: Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open‐label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Methods: Thirty‐four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15μg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and 18F‐dopa uptake. Results: At 6 months, mean percentage changes in “off” UPDRS motor score were −10.0% and −4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, −23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean 18F‐dopa influx constant (p = 0.019) was observed. Serious, device‐related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on‐study and two in the open‐label extension). Interpretation: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F‐dopa uptake. It is uncertain whether technical differences between this trial and positive open‐label studies contributed in any way this negative outcome. Ann Neurol 2006</abstract><note type="funding">Amgen Inc.</note><note type="funding">Medtronic, Inc.</note><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>59</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>459</start><end>466</end><total>8</total></extent></part></relatedItem><identifier type="istex">6CFE15E0209DCA843C277139795F853D5A1C135C</identifier><identifier type="DOI">10.1002/ana.20737</identifier><identifier type="ArticleID">ANA20737</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2006 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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