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Nabilone for non-motor symptoms of Parkinson's disease: a randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study (The NMS-Nab Study).

ABSTRACT: Although open-label observations report a positive effect of cannabinoids on non-motor symptoms (NMS) in Parkinson's disease (PD) patients, these effects remain to be investigated in a controlled trial for a broader use in NMS in PD patients. Therefore, we decided to design a proof-of-concept study to assess the synthetic cannabinoid nabilone for the treatment of NMS. We hypothesize that nabilone will improve NMS in patients with PD and have a favorable safety profile. The NMS-Nab Study is as a mono-centric phase II, randomized, placebo-controlled, double-blind, parallel-group, enriched enrollment withdrawal study. The primary efficacy criterion will be the change in Movement Disorders Society-Unified Parkinson's Disease-Rating Scale Part I score between baseline (i.e. randomization) and week 4. A total of 38 patients will have 80% power to detect a probability of 0.231 that an observation in the treatment group is less than an observation in the placebo group using a Wilcoxon rank-sum test with a 0.050 two-sided significance level assuming a true difference of 2.5 points between nabilone and placebo in the primary outcome measure and a standard deviation of the change of 2.4 points. The reduction of harm through an ineffective treatment, the possibility of individualized dosing, the reduction of sample size, and the possible evaluation of the influence of the placebo effect on efficacy outcomes justify this design for a single-centered placebo-controlled investigator-initiated trial of nabilone. This study should be the basis for further evaluations of long-term efficacy and safety of the use of cannabinoids in PD patients.

SUBMITTER: Peball M

PROVIDER: S-EPMC6647387 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Nabilone for non-motor symptoms of Parkinson's disease: a randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study (The NMS-Nab Study).

Peball Marina M Werkmann Mario M Ellmerer Philipp P Stolz Raphaela R Valent Dora D Knaus Hans-Günther HG Ulmer Hanno H Djamshidian Atbin A Poewe Werner W Seppi Klaus K

Journal of neural transmission (Vienna, Austria : 1996) 20190525 8

Although open-label observations report a positive effect of cannabinoids on non-motor symptoms (NMS) in Parkinson's disease (PD) patients, these effects remain to be investigated in a controlled trial for a broader use in NMS in PD patients. Therefore, we decided to design a proof-of-concept study to assess the synthetic cannabinoid nabilone for the treatment of NMS. We hypothesize that nabilone will improve NMS in patients with PD and have a favorable safety profile. The NMS-Nab Study is as a ...[more]

PMID: 31129719

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Project description:BackgroundNo pharmacological treatments are specifically indicated for painful small fibre neuropathy (SFN). CONVEY, a phase 2 enriched-enrolment study, evaluated the efficacy and safety of vixotrigine, a voltage- and use-dependent sodium channel blocker, in participants with idiopathic or diabetes-associated painful SFN.MethodsCONVEY was a phase 2, multicentre, placebo-controlled, double-blind (DB), enriched-enrolment, randomised withdrawal study. The study was conducted at 68 sites in 13 countries (Europe and Canada) between May 17, 2018, and April 12, 2021. Following a 4-week open-label period in which 265 adults with painful SFN (a mixture of large and small fibre neuropathy was not exclusionary) received oral vixotrigine 350 mg twice daily (BID), 123 participants (with a ≥30% reduction from baseline in average daily pain [ADP] score during the open-label period) were randomised 1:1:1 to receive 200 mg BID, 350 mg BID or placebo for a 12-week double-blind (DB) period. Primary endpoint was change from baseline in ADP at DB Week 12. Secondary endpoints included the proportion of participants with a ≥30% reduction from baseline in ADP and the proportion of Patient Global Impression of Pain (PGIC) responders at DB Week 12. Treatment-emergent adverse events (AEs) were monitored. Statistical significance was set at 0.10 (2-sided). The trial was registered on ClinicalTrials.gov (NCT03339336) and on ClinicalTrialsregister.eu (2017-000991-27).FindingsA statistically significant difference from placebo in least squares mean reduction in ADP score from baseline to DB Week 12 was observed with vixotrigine 200 mg BID (-0.85; SE, 0.43; 95% CI, -1.71 to 0.00; p = 0.050) but not 350 mg BID (-0.17; SE, 0.43; 95% CI, -1.01 to 0.68; p = 0.70). Numerically, but not statistically significantly, more participants who received vixotrigine vs placebo experienced a ≥30% ADP reduction from baseline (68.3-72.5% vs 52.5%), and only the 350 mg BID group had significantly more PGIC responders vs placebo (48.8% vs 30.0%; odds ratio = 2.60; 95% CI, 0.97-6.99; p = 0.058) at DB Week 12. AEs were mostly mild to moderate in the vixotrigine groups. The most common AEs (≥5% of vixotrigine-treated participants) in the DB 200 mg BID and 350 mg BID vixotrigine groups were falls, nasopharyngitis, muscle spasm, and urinary tract infection.InterpretationIn our study, vixotrigine 200 mg BID, but not 350 mg BID, met the primary endpoint; more vixotrigine-treated participants experienced a ≥30% reduction from baseline in ADP at DB Week 12. Vixotrigine (at both dosages) was well tolerated in participants with SFN.FundingBiogen, Inc.

Project description:BACKGROUND AND OBJECTIVES:We assessed the safety, tolerability, and preliminary efficacy of nabilone, a cannabinoid agonist, to treat cannabis dependence. METHODS:Eighteen adults with DSM-IV cannabis dependence were randomized to receive either 2?mg/day of nabilone (n?=?10) or placebo (n?=?8) for 10 weeks in addition to medication management. Twelve participants, six in each group, completed treatment. The safety and tolerability of nabilone was assessed at each visit. Any side effects from nabilone or the placebo were documented. Cannabis use outcomes were assessed via self-report of days of use and twice-weekly urine cannabinoid tests; secondary outcomes included cannabis craving and anxiety. RESULTS:We assessed safety and tolerability at each study visit. A total of eight adverse events, all mild or moderate, were reported in two participants in the nabilone group, and six events were reported in four participants in the placebo group during study treatment. A total of eight adverse events were reported in two participants in the nabilone group and six events were reported in four participants in the placebo group during study treatment. All reported adverse events were rated mild-to-moderate. There were no side effects deemed serious enough to be classified as an FDA-defined serious adverse event. In general, participants in both groups reported reduced cannabis use according to self-report over the course of the study, although these reductions were not statistically discernible. Moreover, there was no difference in cannabis use between the nabilone group and the placebo group as measured by self-report. DISCUSSION AND CONCLUSIONS:Nabilone pharmacotherapy was safe and well-tolerated in participants with cannabis dependence. Future studies might evaluate a higher dose of nabilone to determine its effects on cannabis use outcomes in participants with cannabis dependence. SCIENTIFIC SIGNIFICANCE:There remains a clear need for additional pharmacotherapy trials for cannabis dependence, and nabilone remains a candidate for such trials. (Am J Addict 2017;26:795-801).

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Dataset Information

Nabilone for non-motor symptoms of Parkinson's disease: a randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study (The NMS-Nab Study).

Publications

Nabilone for non-motor symptoms of Parkinson's disease: a randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study (The NMS-Nab Study).

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