A Study of Tolerability and Efficacy of Cannabidiol on Tremor in Parkinson's Disease

NCT02818777 | Completed Phase 2 Results DMC

• 1 other identifier: 15-0929
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The major purpose of the Stage 1 is to study the safety and tolerability of the proposed dosage regimen of the study drug. The form of cannabidiol (CBD) used in this study is GWP42003, supplied by GW Pharmaceuticals. The dosage regime is based on their experience. This is an open label study in 10 subjects, during which the dose is gradually increased to the manufacturers recommended target dose, with tolerability being evaluated at each dose level. Based on the response of subjects in the Stage 1, a target dose is determined for the next stage. Standardized tools will be administered to study both tolerability and efficacy. Efficacy assessments are simply explorative, and are done to look for an effect that warrants specific or different evaluation in the next stage.

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease; Tremor; tolerability; safety; cognition; anxiety; psychosis; mood; dyskinesia; cannabidiol; cannabis; efficacy; sleep; motor symptoms; non-motor symptoms; quality of life; marijuana

Outcome Measures

Primary Outcomes (19)

• Severity of Participants Reporting Study-related Adverse Events at Each Dose Level

  Severity of each specific adverse event was scored as 0=no adverse event, 1=mild adverse event, 2=moderate adverse event, and 3=sever adverse event. The range of severity is 0-3. Higher scores mean a worse outcome. The severity was expressed as mean (standard deviation).

  Every 3rd day on each dose level, assessed up to 5 weeks

• Number of Participants Had Changes in Orthostatic Blood Pressure

  Orthostatic blood pressure will be monitored at each study visit.

  Baseline and 5 weeks

• Number of Participants Had Changes in Physical Exam

  A physical exam will be performed at each study visit.

  Baseline and 5 weeks

• Number of Participants Had Changes in EKG

  EKG will be performed at each study visit.

  Baseline and 5 weeks

• Number of Participants Had Changes in Laboratory Values

  Laboratory tests (hematology, serum chemistry, and urinalysis) will be evaluated at each study visit.

  Baseline and 5 weeks

• Proportion of Subjects That Drop Out of the Study Due to Study Drug Intolerance

  Assessing the proportion of subjects that drop out of the study due to study drug intolerance.

  Baseline and 5 weeks

• Change in Movement Disorder Society-Unified Parkinsons Disease Rating Scale Total Score

  There are four parts: Part I (Non-motor experiences of daily living, scores range 0-52), Part II (motor experiences of daily living, scores range 0-52), Part III (motor examination, scores range 0-132) and Part IV (motor complications scores range 0-24). Subscales are summed to a total score, ranging 0-260. Higher scores mean a worse outcome.

  Baseline and 5 weeks

• Change in Montreal Cognitive Assessment (MoCA)

  MoCA - is designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visual -constructional skills, conceptual thinking, calculation. Scores range 0-30. Higher values represent a better outcome.

  Baseline and 5 weeks

• Change in Anxiety Short Form

  This includes 8 items that assess severity of anxiety. Scores range 8-40. Higher values represent a worse outcome.

  Baseline and 5 weeks

• Change in Neuropsychiatric Inventory (NPI)

  Assessing neuropsychiatric symptoms and psychopathology of patients with Alzheimer's disease and other neurodegenerative disorders. It has proven to be sensitive to change and has been employed to capture treatment related behavioral.Total NPI scores range 0-120. Higher values represent a worse outcome.

  Baseline and 5 weeks

• Change in Depression Short Form

  This includes 8 items that assess severity of depression. Score range 8-40. Higher values represent a worse outcome.

  Baseline and 5 weeks

• Change in Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep-night Time Sleep

  A valid, reliable, short scale that is used to evaluate night time sleep problems in PD. Scores range 0-18. Higher values represent a worse outcome.

  Baseline and 5 weeks

• Change From Baseline of REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)

  10-item, patient self-rating instrument assessing the subject's sleep behavior with short questions that have to be answered by either "yes" or "no". Scores range 0-13. Higher values represent a worse outcome.

  Baseline and 5 weeks

• Change in Emotional and Behavioral Dyscontrol Short Form

  8 items that assess severity of emotional and behavioral dyscontrol. Scores range 8-40. Higher values represent a worse outcome.

  Baseline and 5 weeks

• Change in Pain Severity Form

  This will assess severity of pain. Scores range 3-15. Higher scores represent a worse outcome.

  Baseline and 5 weeks

• Change in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)

  To measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. Total QUIP-RS scores were summed by 6 subscores (gambling 0-16, Sex 0-16, Buying 0-16, Eating 0-16, Hobbyism-punding 0-32, and PD Medication use 0-16), range 0-112. Higher scores represent a worse outcome.

  Baseline and 5 weeks

• Change in Fatigue Severity Scale

  A self-report 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity. Scores range 9-63. Higher values represent a worse outcome.

  Baseline and 5 weeks

• Change in International Restless Legs Syndrome Study Group Rating Scale for Restless

  This encompasses a ten-question instrument for measuring severity of restless legs syndrome (RLS). Score range 0-40. Higher values represent a worse outcome.

  Baseline and 5 weeks

• Change in Unified Dyskinesia Rating Scale (UDysRS)

  To evaluate involuntary movements often associated with treated Parkinson's disease. Total UDysRS scores is the sum of historical sub-scores (0-60) and objective sub-score (0-44). Total scores range 0-104. Higher values represent a worse outcome.

  Baseline and 5 weeks

Secondary Outcomes (1)

• Change in MDS-UPDRS Tremor Score (Total of Items 3.17 and 3.18) in the ON State

  Baseline and 5 weeks

Study Arms (1)

cannabidiol

EXPERIMENTAL

GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day.

Drug: cannabidiol

Interventions

cannabidiol DRUG

Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties.

Also known as: GWP42003-P

cannabidiol

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects between 45 and 78 years of age inclusive.
• Willing and able to give informed consent.
• Idiopathic PD, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria
• Rest tremor amplitude score of ≥2 in any limb on question 3.17 of the MDS-UPDRS (ON state).
• Anti-parkinsonian medication is fixed for at least 1 month prior to study entry
• If MoCA\<22 subject must have a legally authorized representative (LAR) sign the consent, and must have a designated caregiver that agrees to ensure study protocols followed. This includes accompanying patient to study visits and being available for study phone calls.
• Must have a driver to drive them to and from study visits
• Has a significant other (someone who knows the subject well) that is appropriate for doing the NPI assessment, can accompany patient to study visits, and agrees to do so
• Agrees to not take more than 1 gram per day of acetaminophen, due to a possible interaction with study drug that could increase risk of hepatotoxicity.

You may not qualify if:

• Known or suspected allergy to cannabinoids or excipients used in the study drug formulation.
• Cannabinoids taken currently or in the previous 30 days.
• History of drug or alcohol dependence; defined by prior inpatient stay(s) for this or that patient stats s/he has a history of this.
• Use of dopamine blockers within 180 days and amphetamine, cocaine, and MAO-A inhibitors within 90 days of baseline.
• Currently taking tolcapone, valproic acid, felbamate, niacin, isoniazid and ketoconazole due to risk of liver injury and clobazam and ketoconazole because of risk of toxic interactions with the study drug. These medications need to be stopped 90 days before the baseline visit.
• Unstable medical condition.
• Any of the following laboratory test results at screening:

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Colorado Department of Public Health and Environment: collaborator
• GW Research Ltd: collaborator

Study Sites (1)

University of Colorado School of Medicine

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Tremor; Anxiety Disorders; Psychotic Disorders; Dyskinesias; Marijuana Abuse

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Maureen Anne Leehey
• Organization: University of Colorado

maureen.leehey@ucdenver.edu

303-724-2194

Study Officials

• Maureen A Leehey, M.D.

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2016
• First Posted: June 30, 2016
• Study Start: October 1, 2016
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: February 19, 2019
• Results First Posted: February 19, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)