PMID- 32757413
OWN - NLM
STAT- MEDLINE
DCOM- 20201214
LR  - 20210110
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 88
IP  - 4
DP  - 2020 Oct
TI  - Non-Motor Symptoms in Parkinson's Disease are Reduced by Nabilone.
PG  - 712-722
LID - 10.1002/ana.25864 [doi]
AB  - OBJECTIVE: The objective of this study was to assess the efficacy and safety of 
      nabilone, a synthetic tetrahydrocannabinol analogue, as a treatment for non-motor 
      symptoms (NMS) in Parkinson's disease (PD). METHODS: This was a phase II 
      placebo-controlled, double-blind, parallel-group, enriched enrollment randomized 
      withdrawal trial conducted at the Medical University Innsbruck. A random sample 
      of 47 patients with PD with stable motor disease and disturbing NMS defined by a 
      score of >/=4 points on the Movement Disorder Society - Unified PD Rating Scale-I 
      (MDS-UPDRS-I) underwent open-label nabilone titration (0.25 mg once daily to 1 mg 
      twice daily, phase I). Responders were randomized 1:1 to continue with nabilone 
      or switch to placebo for 4 weeks (phase II). The primary efficacy criterion was 
      the change of the MDS-UPDRS-I between randomization and week 4. Safety was 
      analyzed in all patients who received at least one nabilone dose. RESULTS: 
      Between October 2017 and July 2019, 19 patients received either nabilone (median 
      dose = 0.75 mg) or placebo. At week 4, mean change of the MDS-UPDRS-I was 2.63 
      (95% confidence interval [CI] 1.53 to 3.74, p = 0.002, effect size = 1.15) in the 
      placebo versus 1.00 (95% CI -0.16 to 2.16, p = 0.280, effect size = 0.42) in the 
      nabilone-group (difference: 1.63, 95% CI 0.09 to 3.18, p = 0.030, effect size = 
      0.66). Seventy-seven percent of patients had adverse events (AEs) during 
      open-label titration, most of them were transient. In the double-blind phase, 
      similar proportions of patients in each group had AEs (42% in the placebo group 
      and 32% in the nabilone group). There were no serious AEs. INTERPRETATION: Our 
      results highlight the potential efficacy of nabilone for patients with PD with 
      disturbing NMS, which appears to be driven by positive effects on anxious mood 
      and night-time sleep problems. TRIAL REGISTRY: ClinicalTrials.gov (NCT03769896) 
      and EudraCT (2017-000192-86). ANN NEUROL 2020;88:712-722.
CI  - (c) 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on 
      behalf of American Neurological Association.
FAU - Peball, Marina
AU  - Peball M
AUID- ORCID: 0000-0002-0791-7300
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Krismer, Florian
AU  - Krismer F
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Knaus, Hans-Gunther
AU  - Knaus HG
AD  - Department for Medical Genetics, Molecular, and Clinical Pharmacology, Innsbruck 
      Medical University, Innsbruck, Austria.
FAU - Djamshidian, Atbin
AU  - Djamshidian A
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Werkmann, Mario
AU  - Werkmann M
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Carbone, Federico
AU  - Carbone F
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Ellmerer, Philipp
AU  - Ellmerer P
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Heim, Beatrice
AU  - Heim B
AUID- ORCID: 0000-0002-6749-3044
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Marini, Kathrin
AU  - Marini K
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Valent, Dora
AU  - Valent D
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Goebel, Georg
AU  - Goebel G
AD  - Department of Medical Statistics, Informatics, and Health Economics, Innsbruck 
      Medical University, Innsbruck, Austria.
FAU - Ulmer, Hanno
AU  - Ulmer H
AD  - Department of Medical Statistics, Informatics, and Health Economics, Innsbruck 
      Medical University, Innsbruck, Austria.
FAU - Stockner, Heike
AU  - Stockner H
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Wenning, Gregor K
AU  - Wenning GK
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Stolz, Raphaela
AU  - Stolz R
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Krejcy, Kurt
AU  - Krejcy K
AD  - AOP Orphan Pharmaceuticals AG, Vienna, Austria.
FAU - Poewe, Werner
AU  - Poewe W
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
FAU - Seppi, Klaus
AU  - Seppi K
AD  - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
CN  - Collaborators of the Parkinson's Disease Working Group Innsbruck
LA  - eng
SI  - ClinicalTrials.gov/NCT03769896
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200831
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 2N4O9L084N (nabilone)
RN  - 7J8897W37S (Dronabinol)
SB  - IM
MH  - Aged
MH  - Anxiety/etiology
MH  - Double-Blind Method
MH  - Dronabinol/*analogs & derivatives/therapeutic use
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Parkinson Disease/complications/*drug therapy
MH  - Sleep Wake Disorders/etiology
MH  - Treatment Outcome
PMC - PMC7540547
COIS- M.P. received travel compensation for presentation of the study data after study 
      end from AOP Orphan Pharmaceuticals AG, which manufactures the drug that is 
      tested in this study. A.D. and B.H. received a travel grant from AOP Orphan 
      Pharmaceuticals AG, which manufactures the study drug. K.K. is an employee at AOP 
      Orphan Pharmaceuticals AG, which manufactured the study drug. K.S. reports 
      personal fees from AOP Orphan Pharmaceuticals AG that manufactures the drug 
      tested in this study. F.K., H.G.K., M.W., F.C., P.E., K.M., D.V., H.S., G.G., 
      H.U., H.K., G.K.W., R.S., and W.P. have no conflict of interest to report.
EDAT- 2020/08/07 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/10/07
CRDT- 2020/08/07 06:00
PHST- 2020/03/28 00:00 [received]
PHST- 2020/07/24 00:00 [revised]
PHST- 2020/07/26 00:00 [accepted]
PHST- 2020/08/07 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/08/07 06:00 [entrez]
PHST- 2020/10/07 00:00 [pmc-release]
AID - ANA25864 [pii]
AID - 10.1002/ana.25864 [doi]
PST - ppublish
SO  - Ann Neurol. 2020 Oct;88(4):712-722. doi: 10.1002/ana.25864. Epub 2020 Aug 31.