Nabilone for Non-motor Symptoms in Parkinson's Disease

NCT03769896 | Completed Phase 2 Results

• 1 other identifier: 1.4
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease

Keywords

Parkinson´s Disease; cannabinoids; non-motor symptoms

Outcome Measures

Primary Outcomes (1)

• Changes of Non-motor Symptoms

  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.

  from baseline to 4 weeks + 2 days

Secondary Outcomes (21)

• Changes in Motor and Different Non-motor Symptoms of PD

  from baseline to 4 weeks + 2 days

• Changes in Different Domains of Non-motor Symptoms of PD

  from baseline to 4 weeks + 2 days

• Changes in Non-motor Symptoms of PD

  from baseline to 4 weeks + 2 days

• Changes in Non-motor Symptoms of PD

  from baseline to 4 weeks + 2 days

• Changes in Non-motor Symptoms of PD

  from baseline to 4 weeks + 2 days

Other Outcomes (2)

• The Exploratory Objective of This Study Will be an Eye-tracking Evaluation in PD Patients Taking Nabilone or Placebo.

  Maximum of 104 days

• The Exploratory Objective of This Study Will be an Eye-tracking Evaluation in PD Patients Taking Nabilone or Placebo.

  Maximum of 104 days

Study Arms (2)

Treatment Group

ACTIVE COMPARATOR

Nabilone 0.25 mg

Drug: Nabilone 0.25 mg

Placebo Group

PLACEBO COMPARATOR

Placebo (corn starch)

Drug: Placebo

Interventions

Nabilone 0.25 mg DRUG

capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis

Treatment Group

Placebo DRUG

capsule, corn starch, daily basis

Placebo Group

Eligibility Criteria

• Age: 30 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥30 years
• Diagnosis of Parkinson´s Disease (PD): PD should be either de novo or on stable medication without disturbing motor fluctuations or dyskinesia.
• NMS with a score of ≥4 on MDS-UPDRS Part 1. One of the following domains have to be affected with a score ≥2: 1.4 (anxious mood) or 1.9 (pain)
• On a stable regimen of anti-parkinson medications for at least 30 days prior to screening and willing to continue the same doses and regimens during study participation
• Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening, and subject must be willing to continue the same doses and regimens during study participation
• Patient is informed and had enough time and opportunity to think about his/her participation in the study and has signed a current Institutional Review Board-approved informed consent form
• Contraception
• Women of childbearing potential must use or attest an acceptable method\* of contraception starting 4 weeks prior to study drug administration and for a minimum of 1 month after study completion.
• Men with a potentially fertile partner must be willing to use an acceptable method of contraception for the duration of the study and for 3 months after study drug discontinuation or have had a vasectomy.

You may not qualify if:

• Patients with any of the following characteristics will be excluded from entering the study:
• Patient previously participated in any study with nabilone.
• Current use of cannabinoids or use of cannabinoids within 30 days prior to screening.
• Patient is currently participating in or has participated in another study of investigational products within 30 days prior to screening.
• Patient has any form of secondary or atypical parkinsonism (e.g., drug-induced, post stroke).
• Patient presents with motor complications which are, based on the investigator's judgment, not adequately controlled (i.e. a score ≥2 on one of the items of the MDS-UPDRS Part IV at screening)
• Hoehn and Yahr stage \> 3
• Evidence of disturbing (i.e. requiring treatment) impulse control disorder in the participant. Can be resolved through a structural interview during screening period.
• History of neurosurgical intervention for PD
• presence of symptomatic orthostatic hypotension at screening (MDS-UPDRS 1.12 \> 2)
• Use of prohibited medication (e.g. benzodiazepines (except for clonazepam up to a maximum of 1.5 mg per d), lithium, opioids, buspirone, muscle relaxing agents, central nervous system depressing substances, ...)
• Patients with laboratory values that are out-of-range at Screening (or within 4 weeks prior to Screening) and haven´t been reviewed and documented as not clinically significant by the investigator. Lab Tests can be repeated for confirmation.
• Patients with known or newly diagnosed sinus tachycardia in ECG evaluation at Screening or within 4 weeks prior to Screening.
• presence of an acute or chronic major psychiatric disorder (e.g., Major Depressive Disorder, psychosis) or symptom (e.g., hallucinations, agitation, paranoia) (MDS-UPDRS 1.2 and/or 1.3 \> 2)
• Patients who had a recent suicidal attempt (active, interrupted, aborted) within the past five years or report suicidal ideation within the past 6 months.

Sponsors & Collaborators

• Medical University Innsbruck: lead

Study Sites (1)

Department of Neurology - Medical University Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Related Publications (2)

• Peball M, Seppi K, Krismer F, Knaus HG, Spielberger S, Heim B, Ellmerer P, Werkmann M, Poewe W, Djamshidian A. Effects of Nabilone on Sleep Outcomes in Patients with Parkinson's Disease: A Post-hoc Analysis of NMS-Nab Study. Mov Disord Clin Pract. 2022 May 31;9(6):751-758. doi: 10.1002/mdc3.13471. eCollection 2022 Aug.

  PMID: 35937495 DERIVED

• Peball M, Krismer F, Knaus HG, Djamshidian A, Werkmann M, Carbone F, Ellmerer P, Heim B, Marini K, Valent D, Goebel G, Ulmer H, Stockner H, Wenning GK, Stolz R, Krejcy K, Poewe W, Seppi K; Collaborators of the Parkinson's Disease Working Group Innsbruck. Non-Motor Symptoms in Parkinson's Disease are Reduced by Nabilone. Ann Neurol. 2020 Oct;88(4):712-722. doi: 10.1002/ana.25864. Epub 2020 Aug 31.

  PMID: 32757413 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

nabilone

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Limitations and Caveats

negative expectations might impact results (due to withdrawal design), sample size of 38 patients (double-blind phase), all caucasian patients

Results Point of Contact

• Title: Prof. Klaus Seppi
• Organization: Medical University of Innsbruck

klaus.seppi@tirol-kliniken.at

004351250481553

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: placebo-controlled, double-blind, parallel-group with 1 : 1 randomization
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 10, 2018
• Study Start: October 3, 2017
• Primary Completion: July 15, 2019
• Study Completion: July 15, 2019
• Last Updated: March 2, 2021
• Results First Posted: March 2, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)