NCT03769896: NMS-Nab

Nabilone for Non-motor Symptoms in Parkinson's Disease

Completed Phase 2 Results posted Last updated 2 March 2021

What this trial tests

Phase 2 trial testing Nabilone 0.25 mg in Parkinson Disease in 48 participants. Completed in 15 July 2019.

Timeline

3 October 2017

Primary endpoint
15 July 2019

15 July 2019

Quick facts

Lead sponsor	Medical University Innsbruck
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	48
Start date	3 October 2017
Primary completion	15 July 2019
Estimated completion	15 July 2019
Sites	1 location across Austria

Drugs / interventions tested

• Nabilone 0.25 mg — full drug profile →
• Placebo

Conditions studied

• Parkinson Disease — all drugs for Parkinson Disease →

Sponsor

Medical University Innsbruck

Who can join

Adults 30 to 100, any sex, with Parkinson Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Changes of Non-motor Symptoms Primary · from baseline to 4 weeks + 2 days

Changes in Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part I minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.

Group	Value	95% CI
Treatment Group	1.00	-0.16 – 2.16
Placebo Group	2.63	1.53 – 3.74

Changes in Motor and Different Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

Changes in Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part II: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome. Part III: minimum points: 0, maximum points: 132, higher score values indicate a worse outcome.

MDS-UPDRS II

Group	Value	95% CI
Treatment Group	0.47	-0.37 – 1.31
Placebo Group	0.90	-0.35 – 2.14

MDS-UPDRS III

Group	Value	95% CI
Treatment Group	0.53	-2.24 – 3.29
Placebo Group	2.63	0.25 – 5.02

Changes in Different Domains of Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

mood/anxiety domain of MDS-UPDRS Part I (items 1.3 and 1.4) and different other domains of NMSS and MDS-UPDRS part I Each items scores 0 to 4 points with higher score values indicating a worse outcome.

MDS-UPDRS 1.3 Depressed Mood

Group	Value	95% CI
Treatment Group	0.11	-0.17 – 0.38
Placebo Group	0.16	-0.08 – 0.40

MDS-UPDRS 1.4 Anxious Mood

Group	Value	95% CI
Treatment Group	-0.16	-0.53 – 0.21
Placebo Group	0.21	-0.05 – 0.47

MDS-UPDRS 1.7 Nighttime sleep problems

Group	Value	95% CI
Treatment Group	0.05	-0.47 – 0.57
Placebo Group	1.79	1.15 – 2.42

Changes in Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome.

Group	Value	95% CI
Treatment Group	4.05	-0.65 – 8.75
Placebo Group	11.00	4.68 – 17.32

Changes in Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

Hospital anxiety and depression scale (HAD-S) Minimum: 0, maximum: 42, higher score values indicate a worse outcome.

Hospital anxiety and depression scale - Anxiety

Group	Value	95% CI
Treatment Group	0.26	-0.87 – 1.40
Placebo Group	0.05	-1.09 – 1.19

Hospital anxiety and depression scale - Depression

Group	Value	95% CI
Treatment Group	0.32	-1.11 – 1.74
Placebo Group	0.16	-0.71 – 1.03

Changes in Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

Epworth Sleepiness Scale (ESS) Minimum: 0, maximum: 24, higher score values indicate a worse outcome.

Group	Value	95% CI
Treatment Group	-0.74	-1.87 – 0.40
Placebo Group	-0.79	-1.85 – 0.27

Changes in Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

Fatigue Severity Scale (FSS) Minimum: 9, maximum: 63, higher score values indicate a worse outcome.

Group	Value	95% CI
Treatment Group	-4.00	-9.77 – 1.77
Placebo Group	0.00	-5.26 – 5.26

Changes in Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

King's Parkinson's disease pain scale (KPPS) Minimum: 0, maximum: 168, higher score values indicate a worse outcome.

Group	Value	95% CI
Treatment Group	1.58	-2.73 – 5.89
Placebo Group	2.84	-5.19 – 10.87

Changes in Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) Minimum: 0, maximum: 112, higher score values indicate a worse outcome.

Group	Value	95% CI
Treatment Group	-0.68	-1.49 – 0.12
Placebo Group	0.05	-0.64 – 0.74

Changes in Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

Montreal Cognitive Assessment (MoCA) Minimum: 0, maximum: 30, higher score values indicate better outcome.

Group	Value	95% CI
Treatment Group	0.74	-0.18 – 1.66
Placebo Group	0.00	-0.63 – 0.62

Changes in Non-motor Symptoms of PD Secondary · from baseline to 4 weeks + 2 days

Visual Analog Scale (VAS) of Pain Minimum: 0 mm, maximum: 10 mm, higher score values indicate a worse outcome.

Group	Value	95% CI
Treatment Group	6.58	-5.65 – 18.81
Placebo Group	2.16	-8.40 – 12.71

Clinical Global Impression - Global Improvement (CGI-I) Scale Secondary · Values of the Termination visit (4 weeks + 2 days from baseline)

Clinical Global Impression - Global Improvement (CGI-I) scale Minimum: 1, maximum: 7, higher score values indicate a worse outcome.

Group	Value	95% CI
Treatment Group	4.95	± 0.71
Placebo Group	4.42	± 0.61

Adverse events — posted to ClinicalTrials.gov

Time frame: Each patient was assessed from first intake of study drug to study discontinuation.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment Group (Open-label Phase)

Serious: 0/47 (0%)

Deaths: 0/47

Treatment Group (Double-blind Phase)

Serious: 0/19 (0%)

Deaths: 0/19

Placebo Group (Double-blind Phase)

Serious: 0/19 (0%)

Deaths: 0/19

Other adverse events (9 terms — click to expand)

Reaction	System	Treatment Group (Open-labe…	Treatment Group (Double-bl…	Placebo Group (Double-blin…
Fatigue	Nervous system disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Pain (including worsening)	Musculoskeletal and connective tissue disorders	—	—	—
Dry mouth	Skin and subcutaneous tissue disorders	—	—	—
Daytime sleepiness	Nervous system disorders	—	—	—
Insomnia	Nervous system disorders	—	—	—
Fall (including recurrent falls)	Musculoskeletal and connective tissue disorders	—	—	—
Syncope	Nervous system disorders	—	—	—

Data from ClinicalTrials.gov NCT03769896 adverse events section.

Sponsor's own description

This is a randomized placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal study assessing the efficacy and safety of nabilone for non-motor symptoms in patients with Parkinson´s Disease. Nabilone is an analogue of tetrahydrocannabinol (THC), the psychoactive component of cannabis. Nabilone acts as a partial agonist on both Cannabinoid 1 (CB1) and Cannabinoid 2 (CB2) receptor in humans and therefore mimics the effect of THC but with more predictable side effects and less euphoria.

Part 1 is an open-label dose adjustment phase of the study. In eligible patients, a screening period is followed by an open-label nabilone dose optimization phase and a stable phase for at least 1 week. Treatment responders will be included in Part 2 of the study (randomized placebo-controlled, double-blind, parallel-grouped).

Part 2 is the placebo-controlled, double-blind, parallel-group randomized withdrawal phase of the study.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inflammation and immune dysfunction in Parkinson disease.
   Tansey MG, Wallings RL, Houser MC, Herrick MK, et al · · 2022 · cited 895× · PMID 35246670 · DOI 10.1038/s41577-022-00684-6
2. Non-Motor Symptoms in Parkinson's Disease are Reduced by Nabilone.
   Peball M, Krismer F, Knaus HG, Djamshidian A, et al · · 2020 · cited 82× · PMID 32757413 · DOI 10.1002/ana.25864
3. Targeting Microglia in Neuroinflammation: H3 Receptor Antagonists as a Novel Therapeutic Approach for Alzheimer's Disease, Parkinson's Disease, and Autism Spectrum Disorder.
   Thomas SD, Abdalla S, Eissa N, Akour A, et al · · 2024 · cited 18× · PMID 39065682 · DOI 10.3390/ph17070831
4. Effects of Nabilone on Sleep Outcomes in Patients with Parkinson's Disease: A Post-hoc Analysis of NMS-Nab Study.
   Peball M, Seppi K, Krismer F, Knaus HG, et al · · 2022 · cited 17× · PMID 35937495 · DOI 10.1002/mdc3.13471
5. 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 M, Werkmann M, Ellmerer P, Stolz R, et al · · 2019 · cited 17× · PMID 31129719 · DOI 10.1007/s00702-019-02021-z
6. Beyond Pain Relief: A Review on Cannabidiol Potential in Medical Therapies.
   Luz-Veiga M, Azevedo-Silva J, Fernandes JC. · · 2023 · cited 15× · PMID 37259306 · DOI 10.3390/ph16020155
7. Clinical trials for cognition in Parkinson's disease: Where are we and how can we do better?
   Bayram E, Batzu L, Tilley B, Gandhi R, et al · · 2023 · cited 13× · PMID 37031010 · DOI 10.1016/j.parkreldis.2023.105385
8. Research progress on the cannabinoid type-2 receptor and Parkinson's disease.
   Yu X, Jia Y, Dong Y. · · 2023 · cited 8× · PMID 38264546 · DOI 10.3389/fnagi.2023.1298166