Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease.
Identifieur interne : 000003 ( PubMed/Checkpoint ); précédent : 000002; suivant : 000004Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease.
Auteurs : Susan H. Fox [Canada] ; Leonard Verhagen Metman [États-Unis] ; John G. Nutt [États-Unis] ; Matthew Brodsky [États-Unis] ; Stewart A. Factor [États-Unis] ; Anthony E. Lang [Canada] ; Laura E. Pope [États-Unis] ; Nadine Knowles [États-Unis] ; João Siffert [États-Unis]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2017.
Abstract
Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia.
DOI: 10.1002/mds.26976
PubMed: 28370447
Affiliations:
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Fox</name><affiliation wicri:level="1"><nlm:affiliation>The Edmond J Safra Program in Parkinson's Disease, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>The Edmond J Safra Program in Parkinson's Disease, University Health Network, Toronto Western Hospital, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Metman, Leonard Verhagen" sort="Metman, Leonard Verhagen" uniqKey="Metman L" first="Leonard Verhagen" last="Metman">Leonard Verhagen Metman</name><affiliation wicri:level="2"><nlm:affiliation>Rush University Medical Center, Chicago, Illinois, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Rush University Medical Center, Chicago, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></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 wicri:level="2"><nlm:affiliation>Oregon Health and Science University, Portland, Oregon, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Oregon Health and Science University, Portland, Oregon</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Brodsky, Matthew" sort="Brodsky, Matthew" uniqKey="Brodsky M" first="Matthew" last="Brodsky">Matthew Brodsky</name><affiliation wicri:level="2"><nlm:affiliation>Oregon Health and Science University, Portland, Oregon, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Oregon Health and Science University, Portland, Oregon</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A" last="Factor">Stewart A. Factor</name><affiliation wicri:level="2"><nlm:affiliation>Emory University, Atlanta, Georgia, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Emory University, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E" last="Lang">Anthony E. Lang</name><affiliation wicri:level="1"><nlm:affiliation>The Edmond J Safra Program in Parkinson's Disease, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>The Edmond J Safra Program in Parkinson's Disease, University Health Network, Toronto Western Hospital, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Pope, Laura E" sort="Pope, Laura E" uniqKey="Pope L" first="Laura E" last="Pope">Laura E. Pope</name><affiliation wicri:level="2"><nlm:affiliation>Avanir Pharmaceuticals, Inc, Aliso Viejo, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Avanir Pharmaceuticals, Inc, Aliso Viejo, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Knowles, Nadine" sort="Knowles, Nadine" uniqKey="Knowles N" first="Nadine" last="Knowles">Nadine Knowles</name><affiliation wicri:level="2"><nlm:affiliation>Avanir Pharmaceuticals, Inc, Aliso Viejo, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Avanir Pharmaceuticals, Inc, Aliso Viejo, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Siffert, Joao" sort="Siffert, Joao" uniqKey="Siffert J" first="João" last="Siffert">João Siffert</name><affiliation wicri:level="2"><nlm:affiliation>Avanir Pharmaceuticals, Inc, Aliso Viejo, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Avanir Pharmaceuticals, Inc, Aliso Viejo, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">28370447</PMID><DateCreated><Year>2017</Year><Month>04</Month><Day>03</Day></DateCreated><DateRevised><Year>2017</Year><Month>04</Month><Day>03</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2017</Year><Month>Mar</Month><Day>30</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.26976</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout. After 14 days, a 2-hour intravenous levodopa-infusion was administered. Patient examinations were videotaped before infusion ("off" state) and every 30 minutes during and afterwards until patients returned to "off." The primary endpoint was dyskinesia-severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area-under-curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical-change, and adverse-events.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">A total of 13 patients were randomized and completed the study (efficacy-evaluable population). Dyskinesia-severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area-under-curve 966.5 vs 1048.8; P = .191 [efficacy-evaluable patients]), and significantly lower in a post-hoc sensitivity analysis of the per-protocol-population (efficacy-evaluable patients with ≥ 80% study-drug-compliance, n = 12) when measured from infusion start to 4-hours post-infusion completion (area-under-curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion-start to return to "off" (13.3 vs 14.9; P = .018 [efficacy-evaluable patients]). A total of 9 patients rated dyskinesia "much/very much improved" on dextromethorphan/quinidine versus 1-patient on placebo. Dextromethorphan/quinidine did not worsen PD-motor scores, was generally well tolerated, and was associated with more frequent adverse events.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa-induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society.</AbstractText><CopyrightInformation>© 2017 International Parkinson and Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fox</LastName><ForeName>Susan H</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>The Edmond J Safra Program in Parkinson's Disease, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Metman</LastName><ForeName>Leonard Verhagen</ForeName><Initials>LV</Initials><AffiliationInfo><Affiliation>Rush University Medical Center, Chicago, Illinois, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nutt</LastName><ForeName>John G</ForeName><Initials>JG</Initials><AffiliationInfo><Affiliation>Oregon Health and Science University, Portland, Oregon, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brodsky</LastName><ForeName>Matthew</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Oregon Health and Science University, Portland, Oregon, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Factor</LastName><ForeName>Stewart A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Emory University, Atlanta, Georgia, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lang</LastName><ForeName>Anthony E</ForeName><Initials>AE</Initials><AffiliationInfo><Affiliation>The Edmond J Safra Program in Parkinson's Disease, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pope</LastName><ForeName>Laura E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>Avanir Pharmaceuticals, Inc, Aliso Viejo, California, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Knowles</LastName><ForeName>Nadine</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Avanir Pharmaceuticals, Inc, Aliso Viejo, California, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Siffert</LastName><ForeName>João</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Avanir Pharmaceuticals, Inc, Aliso Viejo, California, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>03</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">AVP-923</Keyword><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">Unified Dyskinesia Rating Scale</Keyword><Keyword MajorTopicYN="N">dextromethorphan/quinidine</Keyword><Keyword MajorTopicYN="N">levodopa-induced dyskinesia</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>08</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2017</Year><Month>01</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>02</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>4</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>4</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>4</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28370447</ArticleId><ArticleId IdType="doi">10.1002/mds.26976</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Californie</li><li>Géorgie (États-Unis)</li><li>Illinois</li><li>Oregon</li></region></list><tree><country name="Canada"><noRegion><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H" last="Fox">Susan H. Fox</name></noRegion><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E" last="Lang">Anthony E. Lang</name></country><country name="États-Unis"><region name="Illinois"><name sortKey="Metman, Leonard Verhagen" sort="Metman, Leonard Verhagen" uniqKey="Metman L" first="Leonard Verhagen" last="Metman">Leonard Verhagen Metman</name></region><name sortKey="Brodsky, Matthew" sort="Brodsky, Matthew" uniqKey="Brodsky M" first="Matthew" last="Brodsky">Matthew Brodsky</name><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A" last="Factor">Stewart A. Factor</name><name sortKey="Knowles, Nadine" sort="Knowles, Nadine" uniqKey="Knowles N" first="Nadine" last="Knowles">Nadine Knowles</name><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G" last="Nutt">John G. Nutt</name><name sortKey="Pope, Laura E" sort="Pope, Laura E" uniqKey="Pope L" first="Laura E" last="Pope">Laura E. 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