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

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ClinicalTrials.gov Identifier: NCT03769896
Recruitment Status : Recruiting
First Posted : December 10, 2018
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
Klaus Seppi, MD, Medical University Innsbruck

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.


Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Nabilone 0.25 mg Drug: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: placebo-controlled, double-blind, parallel-group with 1 : 1 randomization
Primary Purpose: Treatment
Official Title: Nabilone for Non-motor Symptoms in Parkinson's Disease: A Randomized Placebo-controlled, Double-blind, Parallel-group, Enriched Enrolment Randomized Withdrawal Study
Actual Study Start Date : October 3, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Nabilone

Arm Intervention/treatment
Active Comparator: Treatment Group
Nabilone 0.25 mg
Drug: Nabilone 0.25 mg
capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis

Placebo Comparator: Placebo Group
Placebo (corn starch)
Drug: Placebo
capsule, corn starch, daily basis




Primary Outcome Measures :
  1. The primary objective of this study is to demonstrate changes of non-motor symptoms in PD patients taking nabilone from baseline to Week 4/Termination visit. [ Time Frame: 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.


Secondary Outcome Measures :
  1. The secondary objectives of this study are to evaluate changes in motor and different non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 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.

    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 objectives of this study are to evaluate changes in different domains of non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 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.

  3. The secondary objectives of this study are to evaluate changes in non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 4 weeks + 2 days ]
    Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome.

  4. The secondary objectives of this study are to evaluate changes in non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 4 weeks + 2 days ]
    Hospital anxiety and depression scale (HAD-S) Minimum: 0, maximum: 42, higher score values indicate a worse outcome.

  5. The secondary objectives of this study are to evaluate changes in non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 4 weeks + 2 days ]
    Epworth Sleepiness Scale (ESS) Minimum: 0, maximum: 24, higher score values indicate a worse outcome.

  6. The secondary objectives of this study are to evaluate changes in non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 4 weeks + 2 days ]
    Fatigue Severity Scale (FSS) Minimum: 9, maximum: 63, higher score values indicate a worse outcome.

  7. The secondary objectives of this study are to evaluate changes in non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 4 weeks + 2 days ]
    King's Parkinson's disease pain scale (KPPS) Minimum: 0, maximum: 168, higher score values indicate a worse outcome.

  8. The secondary objectives of this study are to evaluate changes in non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 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.

  9. The secondary objectives of this study are to evaluate changes in non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 4 weeks + 2 days ]
    Montreal Cognitive Assessment (MoCA) Minimum: 0, maximum: 30, higher score values indicate better outcome.

  10. The secondary objectives of this study are to evaluate changes in non-motor symptoms of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 4 weeks + 2 days ]
    Visual Analog Scale (VAS) of Pain Minimum: 0 mm, maximum: 10 mm, higher score values indicate a worse outcome.

  11. Moreover, Clinical Global Impression - Global Improvement (CGI-I) scale at Termination Visit will be a secondary objective of this study. [ Time Frame: Maximum of 104 days ]
    Clinical Global Impression - Global Improvement (CGI-I) scale Minimum: 1, maximum: 7, higher score values indicate a worse outcome.

  12. The safety objective of this study is to evaluate the incidence of AEs and number of withdrawals in PD patients taking nabilone. [ Time Frame: 4 weeks + 2 days ]

    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)


  13. The safety objective of this study is to evaluate suicidality in PD patients taking nabilone using the Columbia-Suicide Severity Rating Scale. [ Time Frame: 4 weeks + 2 days ]

    Change in aggregated data 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 anwer "no" indicates no wish to be dead, no suicidal ideations, or suicidal attempts.

    No minimum or maximum score values can be provided.


  14. The safety objective of this study is to evaluate hallucinations in PD patients taking nabilone: MDS-UPDRS [ Time Frame: 4 weeks + 2 days ]
    Changes in points of the Hallucination item (1.2) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome

  15. The safety objective of this study is to evaluate Orthostatic hypotension in PD patients taking nabilone: MDS-UPDRS [ Time Frame: 4 weeks + 2 days ]
    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 and a maximum of 4 points with higher score values representing a worse outcome

  16. The safety objective of this study is to evaluate Day-time sleepiness in PD patients taking nabilone: MDS-UPDRS [ Time Frame: 4 weeks + 2 days ]
    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 and a maximum of 4 points with higher score values representing a worse outcome

  17. The safety objective of this study is to evaluate subject compliance in PD patients taking nabilone. [ Time Frame: 4 weeks + 2 days ]
    subject compliance as per drug accountability (%)

  18. The safety objective of this study is to evaluate changes in weight (kg) in PD patients taking nabilone. [ Time Frame: 4 weeks + 2 days ]
    changes in weight (kg)

  19. The safety objective of this study is to evaluate changes in temperature (degree Celsius) in PD patients taking nabilone. [ Time Frame: 4 weeks + 2 days ]
    changes in temperature (degree Celsius)

  20. The safety objective of this study is to evaluate changes in supine and standing blood pressure measurements (mmHg) in PD patients taking nabilone. [ Time Frame: 4 weeks + 2 days ]
    changes in supine and standing blood pressure measurements (mmHg)

  21. The secondary objective of this study is to evaluate changes in quality of life of PD by means of the change from baseline to Week 4/Termination visit in the following scale: [ Time Frame: 4 weeks + 2 days ]
    Parkinson´s Disease Questionnaire - 39 (PDQ-39) Minimum: 0, maximum: 156, higher score values indicate a worse outcome.


Other Outcome Measures:
  1. The exploratory objective of this study will be an Eye-tracking evaluation in PD patients taking nabilone or placebo. [ Time Frame: Maximum of 104 days ]
    Change of the reaction time (seconds) between the Screening visit (Part 1) and the Termination visit (Part 2) 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 or placebo. [ Time Frame: Maximum of 104 days ]
    Change of attention span and ability to concentrate (error rate, correct trials) between the Screening visit (Part 1) and the Termination visit (Part 2) as measured by the Eye-tracking examination.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 the study subjects must meet all inclusion criteria:

  1. Age ≥30 years
  2. Diagnosis of PD: PD should be either de novo or on stable medication without disturbing motor fluctuations or dyskinesia.
  3. 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)
  4. 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
  5. 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
  6. Patient is informed and had enough time and opportunity to think about his/her participation in the study and has signed a current IRB-approved informed consent form
  7. Contraception

    1. 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.
    2. 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.

Exclusion Criteria:

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

  1. Patient previously participated in any study with nabilone.
  2. Current use of cannabinoids or use of cannabinoids within 30 days prior to screening.
  3. Patient is currently participating in or has participated in another study of investigational products within 30 days prior to screening.
  4. Patient has any form of secondary or atypical parkinsonism (e.g., drug-induced, post stroke).
  5. 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)
  6. Hoehn and Yahr stage > 3
  7. Evidence of disturbing (i.e. requiring treatment) impulse control disorder in the participant. Can be resolved through a structural interview during screening period.
  8. History of neurosurgical intervention for PD
  9. presence of symptomatic orthostatic hypotension at screening (MDS-UPDRS 1.12 > 2)
  10. 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, CNS depressing substances, ...)
  11. 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.
  12. Patients with known or newly diagnosed sinus tachycardia in ECG evaluation at Screening or within 4 weeks prior to Screening.
  13. 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)
  14. Patients who had a recent suicidal attempt (active, interrupted, aborted) within the past five years or report suicidal ideation within the past 6 months.
  15. presence of dementia (MDS-UPDRS 1.1 > 2, MMSE of <24 at the Screening visit)
  16. 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).
  17. Patients with moderate or severe hepatic or renal impairment.
  18. Patient has a history of chronic alcohol or drug abuse within the last 2 years.
  19. women of child-bearing potential who do not practice an acceptable method of birth control
  20. Pregnant women or women planning to become pregnant during the course of the study and nursing women.
  21. Patients who are knowingly hypersensitive to any of the components of the investigational medicinal product or excipients.
  22. Patient is legally incapacitated or persons held in an institution by legal or official order
  23. Persons with any kind of dependency on the investigator or employed by the Sponsor or investigator

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): NCT03769896


Contacts
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Contact: Klaus Seppi, Prof. MD 0043512504 ext 25810 klaus.seppi@tirol-kliniken.at
Contact: Marina Peball, MD 0043512504 ext 82718 marina.peball@tirol-kliniken.at

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: Sweta Bajaj, MD         
Sub-Investigator: Beatrice Heim, MD         
Sub-Investigator: Atbin Djamshidian-Tehrani, MD         
Sub-Investigator: Hans-Günther Knaus, Prof. MD         
Sub-Investigator: Katarzyna Wachowicz, PhD         
Sub-Investigator: Philipp Ellmerer, MD         
Sub-Investigator: Federico Carbone, MD         
Sub-Investigator: Dora Valent, M.Sc.         
Sponsors and Collaborators
Medical University Innsbruck

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Responsible Party: Klaus Seppi, MD, Principal Investigator, Medical University Innsbruck
ClinicalTrials.gov Identifier: NCT03769896     History of Changes
Other Study ID Numbers: 1.4
First Posted: December 10, 2018    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018
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

Keywords provided by Klaus Seppi, MD, Medical University Innsbruck:
Parkinson´s Disease
cannabinoids
non-motor symptoms

Additional relevant MeSH terms:
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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
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists