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Nabilone for Non-motor Symptoms in Parkinson's Disease (NMS-Nab2)

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ClinicalTrials.gov Identifier: NCT03773796
Recruitment Status : Recruiting
First Posted : December 12, 2018
Last Update Posted : September 23, 2019
Sponsor:
Information provided by (Responsible Party):
Klaus Seppi, MD, Medical University Innsbruck

Brief Summary:

This is an open-label extension study for participants of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal NMS-Nab Study, assessing the long-term safety and efficacy 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.

Eligible patients will be re-tapered in an open-label nabilone dose optimization phase followed by an open-label period of 6 months on a stable nabilone dose.


Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Nabilone 0.25 mg Phase 3

Detailed Description:

This is an open-label extension study for participants of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal NMS-Nab Study, assessing the long-term safety and efficacy of nabilone for non-motor symptoms in patients with Parkinson´s Disease. Nabilone is an analogue of tetrahydrocannabinol (THC), the psychoactive component of cannabis.

Eligible subjects will be re-tapered with open-label nabilone, optimally up to the dose the patient had in the NMS-Nab Trial. It is the investigator´s decision to modify this dose, if necessary. The re-tapering will be performed up to a maximum dose of 1 mg twice daily. Treatment responders will enter the open-label treatment period for 6 months with visits being performed every 3 months in the context of the patient´s regularly scheduled visits in the specialized outpatient department. The last visit will be the Termination Visit. Following this, nabilone will be tapered. During this period the patients will receive phone calls every other day. A Safety Follow-Up Visit will be performed.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Intervention Model Description: open-label
Masking: None (Open Label)
Masking Description: None, open-label
Primary Purpose: Treatment
Official Title: Nabilone for Non-motor Symptoms in Parkinson's Disease: An Open-label Study to Evaluate Long-term Safety and Efficacy
Actual Study Start Date : August 6, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Nabilone

Arm Intervention/treatment
Treatment Group
Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg
Drug: Nabilone 0.25 mg
capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
Other Name: Canemes




Primary Outcome Measures :
  1. The primary objective of this study is to evaluate AEs in PD patients taking nabilone. [ Time Frame: 6 months ]

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

    Adverse Events (AE)


  2. The primary objective of this study is to evaluate the incidence of AEs in PD patients taking nabilone. [ Time Frame: 6 months ]

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

    Number of subjects (%) who discontinue the study due to an AE The reasons for discontinuation will be grouped in "discontinuation due to an AE" and "discontinuation due to other reasons". Both results will be provided separately.


  3. The primary objective of this study is to evaluate the number of withdrawals in PD patients taking nabilone. [ Time Frame: 6 months ]

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

    Number of subjects (%) who discontinue the study due to other reasons than an AE The reasons for discontinuation will be grouped in "discontinuation due to an AE" and "discontinuation due to other reasons". Both results will be provided separately.


  4. The primary objective of this study is to evaluate suicidality in PD patients taking nabilone using the Columbia-Suicide Severity Rating Scale. [ Time Frame: 6 months ]

    Change in aggregated data of the Columbia-Suicide Severity Rating Scale (C-SSRS).

    Different questions for suicidality with the possible answers yes or no. Yes represents a worse outcome.


  5. The primary objective of this study is to evaluate hallucinations in PD patients taking nabilone. [ Time Frame: 6 months ]

    Changes in points of the:

    Hallucination item (1.2) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.


  6. The primary objective of this study is to evaluate day-time sleepiness in PD patients taking nabilone. [ Time Frame: 6 months ]

    Changes in points of the:

    Day-time sleepiness item (1.8) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS)

    Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.


  7. The primary objective of this study is to evaluate orthostatic hypotension in PD patients taking nabilone. [ Time Frame: 6 months ]

    Changes in points of the:

    Othostatic hypotension item (1.12) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS)

    Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.


  8. The primary objective of this study is to evaluate subject compliance in PD patients taking nabilone. [ Time Frame: 6 months ]
    subject compliance as per drug accountability (%)

  9. The primary objective of this study is to evaluate changes in weight (kg) in PD patients taking nabilone. [ Time Frame: 6 months ]
    changes in weight (kg)

  10. The primary objective of this study is to evaluate changes in temperature (degree Celsius) in PD patients taking nabilone. [ Time Frame: 6 months ]
    changes in temperature (degree Celsius)

  11. The primary objective of this study is to evaluate changes in supine and standing blood pressure measurements (mmHg) in PD patients taking nabilone. [ Time Frame: 6 months ]
    changes in supine and standing blood pressure measurements (mmHg)


Secondary Outcome Measures :
  1. The secondary objective of the study is to assess changes in motor and non-motor symptoms in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

    Total and different parts of 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.

    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.

    Part IV: minimum points: 0, maximum points: 24, higher score values indicate a worse outcome.

    Total Score: minimum points: 0, maximum points: 272, higher score values indicate a worse outcome.


  2. The secondary objective of the study is to assess changes in non-motor symptoms (MDS-UPDRS Part I) in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

    Different domains of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part I Each items scores 0 to 4 points with higher score values indicating a worse outcome.


  3. The secondary objective of the study is to assess changes in non-motor symptoms (NMSS) in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

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


  4. The secondary objective of the study is to assess changes in non-motor symptoms (HAD-S) in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

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


  5. The secondary objective of the study is to assess changes in quality of life in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

    Parkinson´s Disease Questionnaire - 8 (PDQ-8) Minimum: 0, maximum: 42, higher score values indicate a worse outcome.


  6. The secondary objective of the study is to assess changes in sleepiness in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

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


  7. The secondary objective of the study is to assess changes in fatigue in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

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


  8. The secondary objective of the study is to assess changes in pain in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

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


  9. The secondary objective of the study is to assess changes in impulsive-compulsive behaviour in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

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


  10. The secondary objective of the study is to assess changes in overall symptoms in patients with PD taking nabilone. [ Time Frame: 6 months ]

    Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:

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


  11. The secondary objective of the study is to assess changes in cognitive function (MoCA) in patients with PD taking nabilone. [ Time Frame: a maximum of 2 years, at study completion ]
    The change of Montreal Cognitive Assessment (MoCA, minimum 0 points, maximum 30 points, higher score values indicate better outcome) score values between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.

  12. The secondary objective of the study is to assess changes in cognitive function (MMSE) in patients with PD taking nabilone. [ Time Frame: a maximum of 2 years, at study completion ]
    The change of Mini Mental State Exam (MMSE, minimum 0 points, maximum 30 points, higher score values indicate better outcome) between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.


Other Outcome Measures:
  1. The exploratory objective of this study will be an Eye-tracking evaluation in PD patients taking nabilone at Visit V 2 to assess changes in reaction time. [ Time Frame: a maximum of 2 years, measurement at V2 visit ]
    Change of the reaction time (seconds), between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.

  2. The exploratory objective of this study will be an Eye-tracking evaluation in PD patients taking nabilone at Visit V 2 to assess changes in attention span. [ Time Frame: a maximum of 2 years, measurement at V2 visit ]
    Change of attention span (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.

  3. The exploratory objective of this study will be an Eye-tracking evaluation in PD patients taking nabilone at Visit V 2 to assess changes in the ability to concentrate. [ Time Frame: a maximum of 2 years, measurement at V2 visit ]
    Change of ability to concentrate (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

In order to be eligible for participation in the study, subjects must meet all inclusion criteria:

  1. In order to be eligible for the study, patients must have completed the double-blind phase of the NMS-Nab trial as responders within the last 2 months.
  2. For patients that completed NMS-Nab Study over 2 months prior to the Screening / Baseline Visit, and meet all other inclusion criteria, eligibility should be discussed on a case-by-case basis.
  3. Only patients without a drug-related serious adverse event (SAE) or moderate or severe AE during the NMS-Nab Study can be included in the study
  4. Patients must be able and willing to provide written informed consent prior to any study related procedure being performed. Patients with a legal guardian should be consented according to local requirements.
  5. Patients must be willing and able to take oral medication and able to comply with the study specific procedures.
  6. The patient is in good health as determined by medical examination and based on the investigator's judgement

Exclusion Criteria:

Patients with any of the following characteristics will be excluded from entering the study:

  1. Patients with PD who have not participated in the randomized double-blind phase of the previous NMS-Nab Study.
  2. Patients that experienced a drug-related SAE or had a moderate or severe AE during the NMS-Nab Study will be excluded in the study.
  3. Patients who are unable or unwilling to comply with the study procedures in the investigator´s opinion.
  4. Patients with any clinically significant or unstable medical or surgical condition at the Screening / Baseline Visit that may preclude safety and the completion of the study participation (based on the investigator's judgement).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03773796


Locations
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Austria
Department of Neurology - Medical University Innsbruck Recruiting
Innsbruck, Tyrol, Austria, 6020
Contact: Klaus Seppi, Prof. MD    004351250425810    klaus.seppi@tirol-kliniken.at   
Sub-Investigator: Marina Peball, MD         
Principal Investigator: Klaus Seppi, Prof. MD         
Sub-Investigator: Mario Werkmann, MD         
Sub-Investigator: Werner Poewe, Prof. MD         
Sub-Investigator: Roberto de Marzi, MD         
Sub-Investigator: Kathrin Marini, MD         
Sub-Investigator: Beatrice Heim, MD         
Sub-Investigator: Atbin Djamshidian-Tehrani, MD         
Sub-Investigator: Hans-Günther Knaus, Prof. MD         
Sub-Investigator: Federico Carbone, MD         
Sub-Investigator: Philipp Ellmerer, MD         
Sub-Investigator: Dora Valent, M.Sc.         
Sub-Investigator: Oliver Schorr, MD         
Sub-Investigator: Marina Casazza, MD         
Sub-Investigator: Anja Weber, PhD         
Sub-Investigator: Sabine Spielberger, MD         
Sponsors and Collaborators
Medical University Innsbruck

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Responsible Party: Klaus Seppi, MD, Principal Investigator, Medical University Innsbruck
ClinicalTrials.gov Identifier: NCT03773796     History of Changes
Other Study ID Numbers: 1.3
First Posted: December 12, 2018    Key Record Dates
Last Update Posted: September 23, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: 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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Klaus Seppi, MD, Medical University Innsbruck:
Parkinson´s Disease
cannabinoids
non-motor symptoms
Additional relevant MeSH terms:
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Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dronabinol
Nabilone
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Hallucinogens
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists