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Parkinson DiseasePhase 2NMS-NabNCT03769896

Nabilone for Non-motor Symptoms in Parkinson's Disease

A Phase 2 study testing Nabilone 0.25 mg in people with Parkinson Disease, run by Medical University Innsbruck at 1 site in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 30 to 100 years
Conditions the study is for
Parkinson Disease
What is being tested?
Nabilone 0.25 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
48 participants
Where
1 siteAustria
Study dates
3 Oct 2017to 15 Jul 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In order to be eligible for the study subjects must meet all inclusion criteria:
  • 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
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  • 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.

Who cannot join

  • 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)
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  • 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.
  • presence of dementia (MDS-UPDRS 1.1 > 2, Mini-Mental State Examination of <24 at the Screening visit)
  • clinically significant or unstable medical or surgical condition at Screening or Baseline visit that may preclude safety and the completion of the study participation (based on the investigator's judgment).
  • Patients with moderate or severe hepatic or renal impairment.
  • Patient has a history of chronic alcohol or drug abuse within the last 2 years.
  • women of child-bearing potential who do not practice an acceptable method of birth control
  • Pregnant women or women planning to become pregnant during the course of the study and nursing women.
  • Patients who are knowingly hypersensitive to any of the components of the investigational medicinal product or excipients.
  • Patient is legally incapacitated or persons held in an institution by legal or official order
  • Persons with any kind of dependency on the investigator or employed by the Sponsor or investigator

Trial locations and contacts

1 site in 1 country.

Austria1 site
  • Department of Neurology - Medical University Innsbruck

    Innsbruck, Tyrol, 6020

Other trials in Austria

About this study

Official title: Nabilone for Non-motor Symptoms in Parkinson's Disease: A Randomized Placebo-controlled, Double-blind, Parallel-group, Enriched Enrolment Randomized Withdrawal Study

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.

Read the detailed 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 the open-label dose adjustment phase of the study. In Part 1, eligible subjects, who have signed the informed consent form at the screening visit, will receive open-label nabilone starting with a dosage of 0.25 mg in the evening. During dose titration and optimization, nabilone will be titrated in 0.25 mg increments (increase by 0.25 mg/ every one to four days) up to a maximum dose of 1 mg twice daily. Patients should be on a stable nabilone dose for at least 1 week afterwards until Baseline Visit (V 0).

Part 2 is the placebo-controlled, double-blind, parallel-group randomized withdrawal phase of the study. At Baseline Visit, treatment responders will be included in Part 2 of the study (randomized placebo-controlled, double-blind, parallel-grouped). Responders are randomized in a 1:1 ratio at Baseline Visit to receive either nabilone or matching placebo for 4 weeks + 2 days. The placebo-controlled, double-blind, randomized withdrawal phase will end with a clinic visit (Termination Visit V 1). Following this, the study medication will be tapered in all patients. During this period the patients will receive phone calls every other day. A Safety Telephone Call and a Safety Follow-Up Visit will be performed.

Being tested
Nabilone 0.25 mg, Placebo
Keywords
Parkinson´s Disease, cannabinoids, non-motor symptoms
Medical subject headings
Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nabilone 0.25 mgDrug

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

  • PlaceboDrug

    capsule, corn starch, daily basis

Study groups in NCT03769896
Study groupRoleWhat they receive
Treatment GroupActive comparatorNabilone 0.25 mg
Receives: Drug: Nabilone 0.25 mg
Placebo GroupPlacebo comparatorPlacebo (corn starch)
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: from baseline to 4 weeks + 2 days

Secondary outcomes (21)
  1. Changes in Motor and Different Non-motor Symptoms of PD

    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.

    Measured: from baseline to 4 weeks + 2 days

  2. Changes in Different Domains of Non-motor Symptoms of PD

    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.

    Measured: from baseline to 4 weeks + 2 days

  3. Changes in Non-motor Symptoms of PD

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

    Measured: from baseline to 4 weeks + 2 days

  4. Changes in Non-motor Symptoms of PD

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

    Measured: from baseline to 4 weeks + 2 days

  5. Changes in Non-motor Symptoms of PD

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

    Measured: from baseline to 4 weeks + 2 days

  6. Changes in Non-motor Symptoms of PD

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

    Measured: from baseline to 4 weeks + 2 days

  7. Changes in Non-motor Symptoms of PD

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

    Measured: from baseline to 4 weeks + 2 days

  8. Changes in Non-motor Symptoms of PD

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

    Measured: from baseline to 4 weeks + 2 days

  9. Changes in Non-motor Symptoms of PD

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

    Measured: from baseline to 4 weeks + 2 days

  10. Changes in Non-motor Symptoms of PD

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

    Measured: from baseline to 4 weeks + 2 days

  11. Clinical Global Impression - Global Improvement (CGI-I) Scale

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

    Measured: Values of the Termination visit (4 weeks + 2 days from baseline)

  12. Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone.

    Safety and tolerability will be evaluated with reference to the following:

    Number of subjects (%) who discontinue the study Number of subjects (%) who discontinue the study due to AE Adverse Events (AE): total number of patients with all adverse events is reported (no reporting threshold)

    Measured: from baseline to 4 weeks + 2 days

  13. Suicidality in PD Patients Taking Nabilone.

    Assessment of aggregated data (suicidality present / no suicidality) of the Columbia-Suicide Severity Rating Scale (C-SSRS). The scale consists of questions for suicidality that can be answered with either "yes" or "no". The answer "no" indicates no wish to be dead, no suicidal ideations, or suicidal attempts.

    No minimum or maximum score values can be provided. The values provided represent the number of patients with (new) suicidality.

    Measured: from baseline to 4 weeks + 2 days

  14. Change in Hallucinations in PD Patients Taking Nabilone

    Number of patients with changes in the points of the Hallucination item (1.2) of the Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS).

    Measured: from baseline to 4 weeks + 2 days

  15. Orthostatic Hypotension in PD Patients Taking Nabilone

    Changes in points of the Orthostatic hypotension (OH) item (1.12) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS), minimum of 0, maximum of 4 points, higher score values representing a worse outcome.

    Measured: from baseline to week 4 + 2 days

  16. Day-time Sleepiness in PD Patients Taking Nabilone: MDS-UPDRS

    Changes in points of the Day-time sleepiness item (1.8) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) , minimum of 0, maximum of 4 points, higher score values representing a worse outcome

    Measured: from baseline to week 4 + 2 days

  17. Subject Incompliance in PD Patients Taking Nabilone

    subject incompliance as per drug accountability.

    Measured: from baseline to week 4 + 2 days

  18. Weight (kg) in PD Patients Taking Nabilone.

    changes in weight (kg)

    Measured: from baseline to week 4 + 2 days

  19. Changes in Temperature (Degree Celsius) in PD Patients Taking Nabilone.

    changes in temperature (degree Celsius)

    Measured: from baseline to week 4 + 2 days

  20. Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone.

    changes in supine and standing blood pressure measurements (mmHg)

    Row titles:

    1. Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at the baseline visit
    2. Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at the week 4 - visit
    3. Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at the baseline visit
    4. Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at the week 4 - visit

    Measured: values from baseline and week 4 + 2 days

  21. Changes in Quality of Life of PD

    Parkinson´s Disease Questionnaire - 39 (PDQ-39) Minimum: 0, maximum: 156, higher score values indicate a worse outcome. Values were standardized = PDQ-39 Summary Index (SI, the score of each subdomain was divided by the number of questions of that domain and then multiplied by hundred, the sum score is the sum of the results of all 8 domains)

    Measured: from baseline to week 4 + 2 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2018
  2. Study start3 Oct 2017
  3. Primary completion15 Jul 2019
  4. Study completion15 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03769896
Sponsor's protocol ID
1.4
Acronym
NMS-Nab
Status last verified
Feb 2021
First submitted
6 Dec 2018
Last updated
2 Mar 2021
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: The results of this study will be published according to the principles of publication policy. There are no arrangements on publication issues with subsiding parties.

Publications

  • 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.

    PubMed 35937495
  • 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.

    PubMed 32757413

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nabilone 0.25 mg in people with Parkinson Disease, run by Medical University Innsbruck at 1 site in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes of Non-motor Symptoms (time frame: from baseline to 4 weeks + 2 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03769896, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2021.

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