A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease
Identifieur interne : 000A70 ( PascalFrancis/Curation ); précédent : 000A69; suivant : 000A71A 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 [Portugal] ; Laurence Negre-Pages [France] ; Santiago Perez-Lloret [France] ; Lucette Lacomblez [France] ; Monique Galitzky [France] ; Jean-Christophe Lemarie [France] ; Jean-Christophe Corvol [France] ; Jonathan M. Brotchie [Canada] ; Laura Bossi [France]Source :
- Fundamental & clinical pharmacology [ 0767-3981 ] ; 2012.
Descripteurs français
- Pascal (Inist)
English descriptors
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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 02). 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.
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Brotchie</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Toronto Western Research Institute, University Health Network</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Bossi, Laura" sort="Bossi, Laura" uniqKey="Bossi L" first="Laura" last="Bossi">Laura Bossi</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Faust Pharmaceutical</s1><s2>Illkirch Graffenstaden</s2><s3>FRA</s3><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0290326</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0290326 INIST</idno><idno type="RBID">Pascal:12-0290326</idno><idno type="wicri:Area/PascalFrancis/Corpus">000182</idno><idno type="wicri:Area/PascalFrancis/Curation">000A70</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease</title><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, Hospital and University Paul Sabatier of Toulouse</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM CIC9023 and UMR 825</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Ferreira, Joaquim" sort="Ferreira, Joaquim" uniqKey="Ferreira J" first="Joaquim" last="Ferreira">Joaquim Ferreira</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neurological Clinical Research Unit. Institute of Molecular Medicine</s1><s2>Lisbon</s2><s3>PRT</s3><sZ>2 aut.</sZ></inist:fA14><country>Portugal</country></affiliation></author><author><name sortKey="Negre Pages, Laurence" sort="Negre Pages, Laurence" uniqKey="Negre Pages L" first="Laurence" last="Negre-Pages">Laurence Negre-Pages</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, Hospital and University Paul Sabatier of Toulouse</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM CIC9023 and UMR 825</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>LN-Pharma, Neurosciences & Neuro-epidemiology research unit</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>3 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Perez Lloret, Santiago" sort="Perez Lloret, Santiago" uniqKey="Perez Lloret S" first="Santiago" last="Perez-Lloret">Santiago Perez-Lloret</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, Hospital and University Paul Sabatier of Toulouse</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM CIC9023 and UMR 825</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Lacomblez, Lucette" sort="Lacomblez, Lucette" uniqKey="Lacomblez L" first="Lucette" last="Lacomblez">Lucette Lacomblez</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Clinical Pharmacology, Hopital Pitié-Salpétriêre</s1><s2>Paris</s2><s3>FRA</s3><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Galitzky, Monique" sort="Galitzky, Monique" uniqKey="Galitzky M" first="Monique" last="Galitzky">Monique Galitzky</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, Hospital and University Paul Sabatier of Toulouse</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM CIC9023 and UMR 825</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Lemarie, Jean Christophe" sort="Lemarie, Jean Christophe" uniqKey="Lemarie J" first="Jean-Christophe" last="Lemarie">Jean-Christophe Lemarie</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Effi-Stat</s1><s2>Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>APHP, Service de Pharntacolngie, Hôpital de la Salpêtriàre</s1><s2>Paris 75013</s2><s3>FRA</s3><sZ>8 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>UMPC, Pharmacologie</s1><s2>Paris</s2><s3>FRA</s3><sZ>8 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>INSERM, CIC 9503</s1><s2>Paris 75013</s2><s3>FRA</s3><sZ>8 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M." last="Brotchie">Jonathan M. Brotchie</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Toronto Western Research Institute, University Health Network</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>9 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Bossi, Laura" sort="Bossi, Laura" uniqKey="Bossi L" first="Laura" last="Bossi">Laura Bossi</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Faust Pharmaceutical</s1><s2>Illkirch Graffenstaden</s2><s3>FRA</s3><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author></analytic><series><title level="j" type="main">Fundamental & clinical pharmacology</title><title level="j" type="abbreviated">Fundam. clin. pharmacol.</title><idno type="ISSN">0767-3981</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Fundamental & clinical pharmacology</title><title level="j" type="abbreviated">Fundam. clin. pharmacol.</title><idno type="ISSN">0767-3981</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Clinical trial</term><term>Dyskinesia</term><term>Glutamate</term><term>Hemostatic</term><term>Motor control</term><term>Naftazone</term><term>Parkinson disease</term><term>Placebo</term><term>Randomization</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Randomisation</term><term>Placebo</term><term>Naftazone</term><term>Maladie de Parkinson</term><term>Dyskinésie</term><term>Glutamate</term><term>Essai clinique</term><term>Hémostatique</term><term>Contrôle moteur</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 02). 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><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0767-3981</s0></fA01><fA02 i1="01"><s0>FCPHEZ</s0></fA02><fA03 i2="1"><s0>Fundam. clin. pharmacol.</s0></fA03><fA05><s2>26</s2></fA05><fA06><s2>4</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease</s1></fA08><fA11 i1="01" i2="1"><s1>RASCOL (Olivier)</s1></fA11><fA11 i1="02" i2="1"><s1>FERREIRA (Joaquim)</s1></fA11><fA11 i1="03" i2="1"><s1>NEGRE-PAGES (Laurence)</s1></fA11><fA11 i1="04" i2="1"><s1>PEREZ-LLORET (Santiago)</s1></fA11><fA11 i1="05" i2="1"><s1>LACOMBLEZ (Lucette)</s1></fA11><fA11 i1="06" i2="1"><s1>GALITZKY (Monique)</s1></fA11><fA11 i1="07" i2="1"><s1>LEMARIE (Jean-Christophe)</s1></fA11><fA11 i1="08" i2="1"><s1>CORVOL (Jean-Christophe)</s1></fA11><fA11 i1="09" i2="1"><s1>BROTCHIE (Jonathan M.)</s1></fA11><fA11 i1="10" i2="1"><s1>BOSSI (Laura)</s1></fA11><fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, Hospital and University Paul Sabatier of Toulouse</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></fA14><fA14 i1="02"><s1>INSERM CIC9023 and UMR 825</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></fA14><fA14 i1="03"><s1>Neurological Clinical Research Unit. Institute of Molecular Medicine</s1><s2>Lisbon</s2><s3>PRT</s3><sZ>2 aut.</sZ></fA14><fA14 i1="04"><s1>LN-Pharma, Neurosciences & Neuro-epidemiology research unit</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>3 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Clinical Pharmacology, Hopital Pitié-Salpétriêre</s1><s2>Paris</s2><s3>FRA</s3><sZ>5 aut.</sZ></fA14><fA14 i1="06"><s1>Effi-Stat</s1><s2>Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ></fA14><fA14 i1="07"><s1>APHP, Service de Pharntacolngie, Hôpital de la Salpêtriàre</s1><s2>Paris 75013</s2><s3>FRA</s3><sZ>8 aut.</sZ></fA14><fA14 i1="08"><s1>UMPC, Pharmacologie</s1><s2>Paris</s2><s3>FRA</s3><sZ>8 aut.</sZ></fA14><fA14 i1="09"><s1>INSERM, CIC 9503</s1><s2>Paris 75013</s2><s3>FRA</s3><sZ>8 aut.</sZ></fA14><fA14 i1="10"><s1>Toronto Western Research Institute, University Health Network</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>9 aut.</sZ></fA14><fA14 i1="11"><s1>Faust Pharmaceutical</s1><s2>Illkirch Graffenstaden</s2><s3>FRA</s3><sZ>10 aut.</sZ></fA14><fA20><s1>557-564</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>14711</s2><s5>354000500841030130</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>27 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0290326</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Fundamental & clinical pharmacology</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>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 02). 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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B02</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC02 i1="03" i2="X"><s0>002B17A01</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Randomisation</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Randomization</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Aleatorización</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Placebo</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Placebo</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Placebo</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Naftazone</s0><s2>NK</s2><s2>FR</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Naftazone</s0><s2>NK</s2><s2>FR</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Naftazona</s0><s2>NK</s2><s2>FR</s2><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Maladie de Parkinson</s0><s2>NM</s2><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Parkinson disease</s0><s2>NM</s2><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s2>NM</s2><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Dyskinésie</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Dyskinesia</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Disquinesia</s0><s5>05</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Glutamate</s0><s2>NK</s2><s2>FX</s2><s5>06</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Glutamate</s0><s2>NK</s2><s2>FX</s2><s5>06</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Glutamato</s0><s2>NK</s2><s2>FX</s2><s5>06</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Essai clinique</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Clinical trial</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Ensayo clínico</s0><s5>07</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Hémostatique</s0><s5>23</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Hemostatic</s0><s5>23</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Hemostático</s0><s5>23</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Contrôle moteur</s0><s5>24</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Motor control</s0><s5>24</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Control motor</s0><s5>24</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>41</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Mouvement involontaire</s0><s5>42</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Involuntary movement</s0><s5>42</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Movimiento involuntario</s0><s5>42</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Trouble neurologique</s0><s5>43</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Neurological disorder</s0><s5>43</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Trastorno neurológico</s0><s5>43</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Aminoacide excitateur</s0><s5>44</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Excitatory aminoacid</s0><s5>44</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Aminoácido excitador</s0><s5>44</s5></fC07><fC07 i1="09" i2="X" l="FRE"><s0>Neurotransmetteur</s0><s5>45</s5></fC07><fC07 i1="09" i2="X" l="ENG"><s0>Neurotransmitter</s0><s5>45</s5></fC07><fC07 i1="09" i2="X" l="SPA"><s0>Neurotransmisor</s0><s5>45</s5></fC07><fN21><s1>219</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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|wiki= Wicri/Canada
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|texte= A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease
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