Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease.
Identifieur interne : 001996 ( Ncbi/Checkpoint ); précédent : 001995; suivant : 001997Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease.
Auteurs : Robert A. Hauser [États-Unis] ; Laurence Salin ; Nolwenn Juhel ; Victor L. KonyagoSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2007.
English descriptors
- KwdEn :
- MESH :
- chemical , therapeutic use : Bicyclo Compounds, Heterocyclic, Neurotransmitter Uptake Inhibitors.
- drug therapy : Parkinson Disease.
- Aged, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Middle Aged, Retrospective Studies.
Abstract
The objective of this study was to evaluate the efficacy and safety of three daily dosages of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) compared to placebo as monotherapy in early Parkinson's disease (PD). In MPTP (1-methyl 4-phenyl-tetrahydropyridine 1,2,3,6)-lesioned marmosets, dopamine reuptake inhibitors have been demonstrated to reverse parkinsonian signs without evoking established dyskinesia. NS 2330 inhibits reuptake of dopamine, serotonin, and norepinephrine. We performed a proof-of-concept, randomized, double-blind trial of NS 2330. Two hundred sixty-one subjects with PD < 5 years and not receiving dopaminergic treatment were randomly assigned to daily treatment with NS 2330 at 0.25 mg, 0.5 mg, 1.0 mg, or placebo. Adjusted mean difference in total Unified Parkinson's Disease Rating Scale (UPDRS) scores from baseline to week 14 was -0.7 (P = 0.64) in the 0.25-mg group, -1.3 (P = 0.41) in the 0.5-mg group, and -1.7 (P = 0.27) in the 1.0-mg group. The adjusted mean difference in total UPDRS score for the highest dose group (1.0 mg/day) was superior to placebo at week 6 (-3.1; P = 0.02), but this effect was not sustained. NS 2330 was generally well tolerated and the most commonly reported adverse events were constipation, insomnia, and dry mouth. Decreased body weight and elevated heart rate were common in the 1.0-mg dosage group. At the dosages tested, NS 2330 did not provide significantly greater benefit than placebo. It is possible that inhibition of dopamine reuptake alone does not provide clinical benefit in early PD, adequate inhibition of dopamine reuptake was not achieved in this study, or countervailing physiologic mechanisms offset the potential benefit.
DOI: 10.1002/mds.21258
PubMed: 17149725
Affiliations:
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Hauser</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University of South Florida and Tampa General Healthcare, NPF Center of Excellence, Tampa, Florida 33606, USA. rhauser@hsc.usf.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of South Florida and Tampa General Healthcare, NPF Center of Excellence, Tampa, Florida 33606</wicri:regionArea><wicri:noRegion>Florida 33606</wicri:noRegion></affiliation></author><author><name sortKey="Salin, Laurence" sort="Salin, Laurence" uniqKey="Salin L" first="Laurence" last="Salin">Laurence Salin</name></author><author><name sortKey="Juhel, Nolwenn" sort="Juhel, Nolwenn" uniqKey="Juhel N" first="Nolwenn" last="Juhel">Nolwenn Juhel</name></author><author><name sortKey="Konyago, Victor L" sort="Konyago, Victor L" uniqKey="Konyago V" first="Victor L" last="Konyago">Victor L. 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Hauser</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University of South Florida and Tampa General Healthcare, NPF Center of Excellence, Tampa, Florida 33606, USA. rhauser@hsc.usf.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of South Florida and Tampa General Healthcare, NPF Center of Excellence, Tampa, Florida 33606</wicri:regionArea><wicri:noRegion>Florida 33606</wicri:noRegion></affiliation></author><author><name sortKey="Salin, Laurence" sort="Salin, Laurence" uniqKey="Salin L" first="Laurence" last="Salin">Laurence Salin</name></author><author><name sortKey="Juhel, Nolwenn" sort="Juhel, Nolwenn" uniqKey="Juhel N" first="Nolwenn" last="Juhel">Nolwenn Juhel</name></author><author><name sortKey="Konyago, Victor L" sort="Konyago, Victor L" uniqKey="Konyago V" first="Victor L" last="Konyago">Victor L. Konyago</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="2007" type="published">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Bicyclo Compounds, Heterocyclic (therapeutic use)</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Neurotransmitter Uptake Inhibitors (therapeutic use)</term><term>Parkinson Disease (drug therapy)</term><term>Retrospective Studies</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Bicyclo Compounds, Heterocyclic</term><term>Neurotransmitter Uptake Inhibitors</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Retrospective Studies</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The objective of this study was to evaluate the efficacy and safety of three daily dosages of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) compared to placebo as monotherapy in early Parkinson's disease (PD). In MPTP (1-methyl 4-phenyl-tetrahydropyridine 1,2,3,6)-lesioned marmosets, dopamine reuptake inhibitors have been demonstrated to reverse parkinsonian signs without evoking established dyskinesia. NS 2330 inhibits reuptake of dopamine, serotonin, and norepinephrine. We performed a proof-of-concept, randomized, double-blind trial of NS 2330. Two hundred sixty-one subjects with PD < 5 years and not receiving dopaminergic treatment were randomly assigned to daily treatment with NS 2330 at 0.25 mg, 0.5 mg, 1.0 mg, or placebo. Adjusted mean difference in total Unified Parkinson's Disease Rating Scale (UPDRS) scores from baseline to week 14 was -0.7 (P = 0.64) in the 0.25-mg group, -1.3 (P = 0.41) in the 0.5-mg group, and -1.7 (P = 0.27) in the 1.0-mg group. The adjusted mean difference in total UPDRS score for the highest dose group (1.0 mg/day) was superior to placebo at week 6 (-3.1; P = 0.02), but this effect was not sustained. NS 2330 was generally well tolerated and the most commonly reported adverse events were constipation, insomnia, and dry mouth. Decreased body weight and elevated heart rate were common in the 1.0-mg dosage group. At the dosages tested, NS 2330 did not provide significantly greater benefit than placebo. It is possible that inhibition of dopamine reuptake alone does not provide clinical benefit in early PD, adequate inhibition of dopamine reuptake was not achieved in this study, or countervailing physiologic mechanisms offset the potential benefit.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Juhel, Nolwenn" sort="Juhel, Nolwenn" uniqKey="Juhel N" first="Nolwenn" last="Juhel">Nolwenn Juhel</name><name sortKey="Konyago, Victor L" sort="Konyago, Victor L" uniqKey="Konyago V" first="Victor L" last="Konyago">Victor L. Konyago</name><name sortKey="Salin, Laurence" sort="Salin, Laurence" uniqKey="Salin L" first="Laurence" last="Salin">Laurence Salin</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Hauser, Robert A" sort="Hauser, Robert A" uniqKey="Hauser R" first="Robert A" last="Hauser">Robert A. Hauser</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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