A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease.
Identifieur interne : 000802 ( PubMed/Curation ); précédent : 000801; suivant : 000803A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease.
Auteurs : Olivier Rascol [France] ; Joaquim Ferreira ; Laurence Nègre-Pages ; Santiago Perez-Lloret ; Lucette Lacomblez ; Monique Galitzky ; Jean-Christophe Lemarié ; Jean-Christophe Corvol ; Jonathan M. Brotchie ; Laura BossiSource :
- Fundamental & clinical pharmacology [ 1472-8206 ] ; 2012.
English descriptors
- KwdEn :
- Aged, Antiparkinson Agents (adverse effects), Antiparkinson Agents (therapeutic use), Cross-Over Studies, Double-Blind Method, Dyskinesias (drug therapy), Female, Humans, Male, Naphthoquinones (adverse effects), Naphthoquinones (therapeutic use), Parkinson Disease (drug therapy), Pilot Projects, Placebos, Single-Blind Method, Treatment Outcome.
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Naphthoquinones.
- chemical , therapeutic use : Antiparkinson Agents, Naphthoquinones.
- drug therapy : Dyskinesias, Parkinson Disease.
- Aged, Cross-Over Studies, Double-Blind Method, Female, Humans, Male, Pilot Projects, Placebos, Single-Blind Method, Treatment Outcome.
Abstract
To explore for the first time the tolerability and efficacy of naftazone in patients with Parkinson's disease (PD). Proof-of-concept, randomized, double-blind, placebo-controlled, multiple-cross-over n-of-1 study in patients with PD with wearing-off and dyskinesias. Naftazone was titrated up to 120 mg/day during an initial single-blind dose-finding phase. Seven patients entered the placebo-controlled phase (four consecutive 28-day cross-overs). Three outcome measures were used to collect preliminary indices of efficacy: (i) 48-h ON-OFF diaries; (ii) Unified PD Rating Scale (UPDRS) part III while ON; (iii) seven-point Likert scale to assess "patients' discomfort caused by dyskinesias" (Q1) and 'disability during OFF-periods' (Q2). A 'responder' analysis (proportion of patients with mean treatment effect [naftazone minus placebo] favoring naftazone over the 4 cross-over periods) was used. Treatment effects were derived from mixed-effects anova. On diaries, 5/7 patients responded to naftazone for 'ON-time with troublesome dyskinesia' (reduced time, treatment effect: -49 [95% CI: -93/-4] min, P = 0.03), 6/7 regarding 'ON-time without troublesome dyskinesia' (increased time, treatment effect: 35 [-19/88], P = 0.2). No trend was observed for 'OFF' time. There were 7/7 'responders' regarding UPDRSIII (reduced score, treatment effect: -2.1[-4.5/0.2], P = 0.08). The 7-point scales did not show clear trends in favor of naftazone (3/7 responders for Q1 and 4/7 for Q2). Four of the seven patients reported adverse events after randomization, mostly related to the CNS (mild: 2, severe: 2). These pilot findings are consistent with preclinical data in primates and support the hypothesis that naftazone may have antiparkinsonian and antidyskinetic effects in humans that deserve further clinical investigation.
DOI: 10.1111/j.1472-8206.2011.00951.x
PubMed: 21585523
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Brotchie</name></author><author><name sortKey="Bossi, Laura" sort="Bossi, Laura" uniqKey="Bossi L" first="Laura" last="Bossi">Laura Bossi</name></author></analytic><series><title level="j">Fundamental & clinical pharmacology</title><idno type="eISSN">1472-8206</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Cross-Over Studies</term><term>Double-Blind Method</term><term>Dyskinesias (drug therapy)</term><term>Female</term><term>Humans</term><term>Male</term><term>Naphthoquinones (adverse effects)</term><term>Naphthoquinones (therapeutic use)</term><term>Parkinson Disease (drug therapy)</term><term>Pilot Projects</term><term>Placebos</term><term>Single-Blind Method</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Naphthoquinones</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Naphthoquinones</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesias</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Cross-Over Studies</term><term>Double-Blind Method</term><term>Female</term><term>Humans</term><term>Male</term><term>Pilot Projects</term><term>Placebos</term><term>Single-Blind Method</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">To explore for the first time the tolerability and efficacy of naftazone in patients with Parkinson's disease (PD). Proof-of-concept, randomized, double-blind, placebo-controlled, multiple-cross-over n-of-1 study in patients with PD with wearing-off and dyskinesias. Naftazone was titrated up to 120 mg/day during an initial single-blind dose-finding phase. Seven patients entered the placebo-controlled phase (four consecutive 28-day cross-overs). Three outcome measures were used to collect preliminary indices of efficacy: (i) 48-h ON-OFF diaries; (ii) Unified PD Rating Scale (UPDRS) part III while ON; (iii) seven-point Likert scale to assess "patients' discomfort caused by dyskinesias" (Q1) and 'disability during OFF-periods' (Q2). A 'responder' analysis (proportion of patients with mean treatment effect [naftazone minus placebo] favoring naftazone over the 4 cross-over periods) was used. Treatment effects were derived from mixed-effects anova. On diaries, 5/7 patients responded to naftazone for 'ON-time with troublesome dyskinesia' (reduced time, treatment effect: -49 [95% CI: -93/-4] min, P = 0.03), 6/7 regarding 'ON-time without troublesome dyskinesia' (increased time, treatment effect: 35 [-19/88], P = 0.2). No trend was observed for 'OFF' time. There were 7/7 'responders' regarding UPDRSIII (reduced score, treatment effect: -2.1[-4.5/0.2], P = 0.08). The 7-point scales did not show clear trends in favor of naftazone (3/7 responders for Q1 and 4/7 for Q2). Four of the seven patients reported adverse events after randomization, mostly related to the CNS (mild: 2, severe: 2). These pilot findings are consistent with preclinical data in primates and support the hypothesis that naftazone may have antiparkinsonian and antidyskinetic effects in humans that deserve further clinical investigation.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21585523</PMID><DateCreated><Year>2012</Year><Month>07</Month><Day>05</Day></DateCreated><DateCompleted><Year>2013</Year><Month>02</Month><Day>04</Day></DateCompleted><DateRevised><Year>2014</Year><Month>11</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1472-8206</ISSN><JournalIssue CitedMedium="Internet"><Volume>26</Volume><Issue>4</Issue><PubDate><Year>2012</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Fundamental & clinical pharmacology</Title><ISOAbbreviation>Fundam Clin Pharmacol</ISOAbbreviation></Journal><ArticleTitle>A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>557-64</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/j.1472-8206.2011.00951.x</ELocationID><Abstract><AbstractText>To explore for the first time the tolerability and efficacy of naftazone in patients with Parkinson's disease (PD). Proof-of-concept, randomized, double-blind, placebo-controlled, multiple-cross-over n-of-1 study in patients with PD with wearing-off and dyskinesias. Naftazone was titrated up to 120 mg/day during an initial single-blind dose-finding phase. Seven patients entered the placebo-controlled phase (four consecutive 28-day cross-overs). Three outcome measures were used to collect preliminary indices of efficacy: (i) 48-h ON-OFF diaries; (ii) Unified PD Rating Scale (UPDRS) part III while ON; (iii) seven-point Likert scale to assess "patients' discomfort caused by dyskinesias" (Q1) and 'disability during OFF-periods' (Q2). A 'responder' analysis (proportion of patients with mean treatment effect [naftazone minus placebo] favoring naftazone over the 4 cross-over periods) was used. Treatment effects were derived from mixed-effects anova. On diaries, 5/7 patients responded to naftazone for 'ON-time with troublesome dyskinesia' (reduced time, treatment effect: -49 [95% CI: -93/-4] min, P = 0.03), 6/7 regarding 'ON-time without troublesome dyskinesia' (increased time, treatment effect: 35 [-19/88], P = 0.2). No trend was observed for 'OFF' time. There were 7/7 'responders' regarding UPDRSIII (reduced score, treatment effect: -2.1[-4.5/0.2], P = 0.08). The 7-point scales did not show clear trends in favor of naftazone (3/7 responders for Q1 and 4/7 for Q2). Four of the seven patients reported adverse events after randomization, mostly related to the CNS (mild: 2, severe: 2). These pilot findings are consistent with preclinical data in primates and support the hypothesis that naftazone may have antiparkinsonian and antidyskinetic effects in humans that deserve further clinical investigation.</AbstractText><CopyrightInformation>© 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rascol</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Clinical Pharmacology, Hospital and University Paul Sabatier of Toulouse, France. rascol@cict.fr</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ferreira</LastName><ForeName>Joaquim</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Nègre-Pages</LastName><ForeName>Laurence</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Perez-Lloret</LastName><ForeName>Santiago</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Lacomblez</LastName><ForeName>Lucette</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Galitzky</LastName><ForeName>Monique</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Lemarié</LastName><ForeName>Jean-Christophe</ForeName><Initials>JC</Initials></Author><Author ValidYN="Y"><LastName>Corvol</LastName><ForeName>Jean-Christophe</ForeName><Initials>JC</Initials></Author><Author ValidYN="Y"><LastName>Brotchie</LastName><ForeName>Jonathan M</ForeName><Initials>JM</Initials></Author><Author ValidYN="Y"><LastName>Bossi</LastName><ForeName>Laura</ForeName><Initials>L</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2011</Year><Month>05</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Fundam Clin Pharmacol</MedlineTA><NlmUniqueID>8710411</NlmUniqueID><ISSNLinking>0767-3981</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009285">Naphthoquinones</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010919">Placebos</NameOfSubstance></Chemical><Chemical><RegistryNumber>15B0523P5L</RegistryNumber><NameOfSubstance UI="C005272">naftazone</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000978" MajorTopicYN="N">Antiparkinson Agents</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018592" MajorTopicYN="N">Cross-Over Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020820" MajorTopicYN="N">Dyskinesias</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009285" MajorTopicYN="N">Naphthoquinones</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010865" MajorTopicYN="N">Pilot Projects</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010919" MajorTopicYN="N">Placebos</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016037" MajorTopicYN="N">Single-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>5</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>5</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>2</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21585523</ArticleId><ArticleId IdType="doi">10.1111/j.1472-8206.2011.00951.x</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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