Placebo influences on dyskinesia in Parkinson's disease
Identifieur interne : 001B15 ( Istex/Corpus ); précédent : 001B14; suivant : 001B16Placebo influences on dyskinesia in Parkinson's disease
Auteurs : Christopher G. Goetz ; Eugene Laska ; Christine Hicking ; Philippe Damier ; Thomas Müller ; John Nutt ; C. Warren Olanow ; Olivier Rascol ; Hermann RussSource :
- Movement Disorders [ 0885-3185 ] ; 2008-04-15.
English descriptors
Abstract
Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo‐associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo‐related dyskinesia improvements and worsening. Because placebo‐associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty‐four subjects received placebo treatment; 178 met criteria for placebo‐associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo‐associated improvement, whereas lower baseline dyskinesia score was associated with placebo‐associated worsening. Placebo‐associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo‐effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo‐induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo‐associated improvements in dyskinesia. The magnitude and variance of placebo‐related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents. © 2007 Movement Disorder Society
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DOI: 10.1002/mds.21897
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ISTEX:26A53AAFCA642D9FC0D0DC629121E408271C161ELe document en format XML
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Goetz</name><affiliation><mods:affiliation>Rush University Medical Center, Chicago, Illinois, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Rush University Medical Center, Suite 755, 1725 West Harrison Street, Chicago, IL</mods:affiliation></affiliation></author><author><name sortKey="Laska, Eugene" sort="Laska, Eugene" uniqKey="Laska E" first="Eugene" last="Laska">Eugene Laska</name><affiliation><mods:affiliation>New York University School of Medicine, New York, New York, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Nathan Kline Institute, Orangeburg, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Hicking, Christine" sort="Hicking, Christine" uniqKey="Hicking C" first="Christine" last="Hicking">Christine Hicking</name><affiliation><mods:affiliation>Merck KGaA, Darmstadt, Germany</mods:affiliation></affiliation></author><author><name sortKey="Damier, Philippe" sort="Damier, Philippe" uniqKey="Damier P" first="Philippe" last="Damier">Philippe Damier</name><affiliation><mods:affiliation>Centre Hospitalo‐universitaire de Nantes, Centre d'Investigation Clinique, Nantes, France</mods:affiliation></affiliation></author><author><name sortKey="Muller, Thomas" sort="Muller, Thomas" uniqKey="Muller T" first="Thomas" last="Müller">Thomas Müller</name><affiliation><mods:affiliation>Ruhr University, Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Nutt, John" sort="Nutt, John" uniqKey="Nutt J" first="John" last="Nutt">John Nutt</name><affiliation><mods:affiliation>Oregon Health Sciences University, Portland, Oregon, USA</mods:affiliation></affiliation></author><author><name sortKey="Warren Olanow, C" sort="Warren Olanow, C" uniqKey="Warren Olanow C" first="C." last="Warren Olanow">C. 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Goetz</name><affiliation><mods:affiliation>Rush University Medical Center, Chicago, Illinois, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Rush University Medical Center, Suite 755, 1725 West Harrison Street, Chicago, IL</mods:affiliation></affiliation></author><author><name sortKey="Laska, Eugene" sort="Laska, Eugene" uniqKey="Laska E" first="Eugene" last="Laska">Eugene Laska</name><affiliation><mods:affiliation>New York University School of Medicine, New York, New York, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Nathan Kline Institute, Orangeburg, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Hicking, Christine" sort="Hicking, Christine" uniqKey="Hicking C" first="Christine" last="Hicking">Christine Hicking</name><affiliation><mods:affiliation>Merck KGaA, Darmstadt, Germany</mods:affiliation></affiliation></author><author><name sortKey="Damier, Philippe" sort="Damier, Philippe" uniqKey="Damier P" first="Philippe" last="Damier">Philippe Damier</name><affiliation><mods:affiliation>Centre Hospitalo‐universitaire de Nantes, Centre d'Investigation Clinique, Nantes, France</mods:affiliation></affiliation></author><author><name sortKey="Muller, Thomas" sort="Muller, Thomas" uniqKey="Muller T" first="Thomas" last="Müller">Thomas Müller</name><affiliation><mods:affiliation>Ruhr University, Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Nutt, John" sort="Nutt, John" uniqKey="Nutt J" first="John" last="Nutt">John Nutt</name><affiliation><mods:affiliation>Oregon Health Sciences University, Portland, Oregon, USA</mods:affiliation></affiliation></author><author><name sortKey="Warren Olanow, C" sort="Warren Olanow, C" uniqKey="Warren Olanow C" first="C." last="Warren Olanow">C. 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Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2008-04-15">2008-04-15</date><biblScope unit="volume">23</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="700">700</biblScope><biblScope unit="page" to="707">707</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">26A53AAFCA642D9FC0D0DC629121E408271C161E</idno><idno type="DOI">10.1002/mds.21897</idno><idno type="ArticleID">MDS21897</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>dyskinesias</term><term>placebo</term><term>randomized clinical trials</term><term>sarizotan</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo‐associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo‐related dyskinesia improvements and worsening. Because placebo‐associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty‐four subjects received placebo treatment; 178 met criteria for placebo‐associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo‐associated improvement, whereas lower baseline dyskinesia score was associated with placebo‐associated worsening. Placebo‐associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo‐effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo‐induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo‐associated improvements in dyskinesia. The magnitude and variance of placebo‐related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents. © 2007 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Christopher G. Goetz MD</name><affiliations><json:string>Rush University Medical Center, Chicago, Illinois, USA</json:string><json:string>Rush University Medical Center, Suite 755, 1725 West Harrison Street, Chicago, IL</json:string></affiliations></json:item><json:item><name>Eugene Laska PhD</name><affiliations><json:string>New York University School of Medicine, New York, New York, USA</json:string><json:string>Nathan Kline Institute, Orangeburg, New York, USA</json:string></affiliations></json:item><json:item><name>Christine Hicking Dipl Stat</name><affiliations><json:string>Merck KGaA, Darmstadt, Germany</json:string></affiliations></json:item><json:item><name>Philippe Damier MD, PhD</name><affiliations><json:string>Centre Hospitalo‐universitaire de Nantes, Centre d'Investigation Clinique, Nantes, France</json:string></affiliations></json:item><json:item><name>Thomas Müller MD</name><affiliations><json:string>Ruhr University, Bochum, Germany</json:string></affiliations></json:item><json:item><name>John Nutt MD</name><affiliations><json:string>Oregon Health Sciences University, Portland, Oregon, USA</json:string></affiliations></json:item><json:item><name>C. Warren Olanow MD</name><affiliations><json:string>Mount Sinai School of Medicine New York, New York, USA</json:string></affiliations></json:item><json:item><name>Olivier Rascol MD, PhD</name><affiliations><json:string>Toulouse University Hospital, INSERM Clinical Investigation Center, Toulouse, France</json:string></affiliations></json:item><json:item><name>Hermann Russ MD, PhD</name><affiliations><json:string>Merck KGaA, Darmstadt, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>placebo</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dyskinesias</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>sarizotan</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>randomized clinical trials</value></json:item></subject><articleId><json:string>MDS21897</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo‐associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo‐related dyskinesia improvements and worsening. Because placebo‐associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty‐four subjects received placebo treatment; 178 met criteria for placebo‐associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo‐associated improvement, whereas lower baseline dyskinesia score was associated with placebo‐associated worsening. Placebo‐associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo‐effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo‐induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo‐associated improvements in dyskinesia. The magnitude and variance of placebo‐related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents. © 2007 Movement Disorder Society</abstract><qualityIndicators><score>7.766</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1984</abstractCharCount><pdfWordCount>4778</pdfWordCount><pdfCharCount>31848</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>249</abstractWordCount></qualityIndicators><title>Placebo influences on dyskinesia in Parkinson's disease</title><refBibs><json:item><author><json:item><name>R de la Fuente‐Fernandez</name></json:item><json:item><name>M Schulzer</name></json:item><json:item><name> Stoessl</name></json:item></author><host><volume>1</volume><pages><last>91</last><first>85</first></pages><author></author><title>Lancet Neurol</title></host><title>The placebo effect in neurological 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neurosurgery</json:string></scienceMetrix></categories><publicationDate>2008</publicationDate><copyrightDate>2008</copyrightDate><doi><json:string>10.1002/mds.21897</json:string></doi><id>26A53AAFCA642D9FC0D0DC629121E408271C161E</id><score>0.12821029</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/26A53AAFCA642D9FC0D0DC629121E408271C161E/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/26A53AAFCA642D9FC0D0DC629121E408271C161E/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/26A53AAFCA642D9FC0D0DC629121E408271C161E/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Placebo influences on dyskinesia in Parkinson's disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Copyright © 2007 Movement Disorder Society</p></availability><date>2008</date></publicationStmt><notesStmt><note type="content">*The authors have confirmed with the Editor that their work complies with the Journal's Editorial policy on ghost‐writing (Movement Disorders, 2005, 20:1536). All authors had full access to the data and confirm the accuracy of the analysis.</note><note>NINOS - No. R21 NSO48594;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Placebo influences on dyskinesia in Parkinson's disease</title><author xml:id="author-1"><persName><forename type="first">Christopher G.</forename><surname>Goetz</surname></persName><roleName type="degree">MD</roleName><affiliation>Rush University Medical Center, Chicago, Illinois, USA</affiliation><affiliation>Rush University Medical Center, Suite 755, 1725 West Harrison Street, Chicago, IL</affiliation></author><author xml:id="author-2"><persName><forename type="first">Eugene</forename><surname>Laska</surname></persName><roleName type="degree">PhD</roleName><affiliation>New York University School of Medicine, New York, New York, USA</affiliation><affiliation>Nathan Kline Institute, Orangeburg, New York, USA</affiliation></author><author xml:id="author-3"><persName><forename type="first">Christine</forename><surname>Hicking</surname></persName><roleName type="degree">Dipl Stat</roleName><affiliation>Merck KGaA, Darmstadt, Germany</affiliation></author><author xml:id="author-4"><persName><forename type="first">Philippe</forename><surname>Damier</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Centre Hospitalo‐universitaire de Nantes, Centre d'Investigation Clinique, Nantes, France</affiliation></author><author xml:id="author-5"><persName><forename type="first">Thomas</forename><surname>Müller</surname></persName><roleName type="degree">MD</roleName><affiliation>Ruhr University, Bochum, Germany</affiliation></author><author xml:id="author-6"><persName><forename type="first">John</forename><surname>Nutt</surname></persName><roleName type="degree">MD</roleName><affiliation>Oregon Health Sciences University, Portland, Oregon, USA</affiliation></author><author xml:id="author-7"><persName><forename type="first">C.</forename><surname>Warren Olanow</surname></persName><roleName type="degree">MD</roleName><affiliation>Mount Sinai School of Medicine New York, New York, USA</affiliation></author><author xml:id="author-8"><persName><forename type="first">Olivier</forename><surname>Rascol</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Toulouse University Hospital, INSERM Clinical Investigation Center, Toulouse, France</affiliation></author><author xml:id="author-9"><persName><forename type="first">Hermann</forename><surname>Russ</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Merck KGaA, Darmstadt, Germany</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2008-04-15"></date><biblScope unit="volume">23</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="700">700</biblScope><biblScope unit="page" to="707">707</biblScope></imprint></monogr><idno type="istex">26A53AAFCA642D9FC0D0DC629121E408271C161E</idno><idno type="DOI">10.1002/mds.21897</idno><idno type="ArticleID">MDS21897</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2008</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo‐associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo‐related dyskinesia improvements and worsening. Because placebo‐associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty‐four subjects received placebo treatment; 178 met criteria for placebo‐associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo‐associated improvement, whereas lower baseline dyskinesia score was associated with placebo‐associated worsening. Placebo‐associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo‐effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo‐induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo‐associated improvements in dyskinesia. 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Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo‐associated improvement, whereas lower baseline dyskinesia score was associated with placebo‐associated worsening. Placebo‐associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo‐effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo‐induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo‐associated improvements in dyskinesia. The magnitude and variance of placebo‐related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents. © 2007 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>The authors have confirmed with the Editor that their work complies with the Journal's Editorial policy on ghost‐writing (Movement Disorders, 2005, 20:1536). 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Placebo‐associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo‐related dyskinesia improvements and worsening. Because placebo‐associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty‐four subjects received placebo treatment; 178 met criteria for placebo‐associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo‐associated improvement, whereas lower baseline dyskinesia score was associated with placebo‐associated worsening. Placebo‐associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo‐effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo‐induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo‐associated improvements in dyskinesia. The magnitude and variance of placebo‐related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents. © 2007 Movement Disorder Society</abstract><note type="content">*The authors have confirmed with the Editor that their work complies with the Journal's Editorial policy on ghost‐writing (Movement Disorders, 2005, 20:1536). All authors had full access to the data and confirm the accuracy of the analysis.</note><note type="funding">NINOS - No. R21 NSO48594; </note><subject lang="en"><genre>keywords</genre><topic>Parkinson's disease</topic><topic>placebo</topic><topic>dyskinesias</topic><topic>sarizotan</topic><topic>randomized clinical trials</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. 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