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

• Register: ClinicalTrials.gov
• Last refreshed on: 28 February 2022
• Main ID: NCT03582137
• Date of registration: 17/04/2018
• Prospective Registration: Yes
• Primary sponsor: University of Colorado, Denver
• Public title: A Study of Tolerability and Efficacy of Cannabidiol on Motor Symptoms in Parkinson's Disease
• Scientific title: A Randomized, Double Blind, Placebo-controlled Parallel Study of Tolerability and Efficacy of Cannabidiol (CBD) on Motor Symptoms in Parkinson's Disease
• Date of first enrolment: September 17, 2018
• Target sample size: 74
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03582137
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Maureen Leehey
• Affiliation: University of Colorado School of Medicine

Key inclusion & exclusion criteria

Inclusion criteria:

- Male or female participants 40 - 85 years of age.

- Willing and able to give informed consent (including through use of a legally
authorized representative (LAR), if necessary).

- Idiopathic PD, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical
Diagnostic Criteria

- ON motor MDS UPDRS >20.

- Anti-parkinsonian medication is fixed for at least one month prior to the day the
participant starts study drug treatment.

- If MoCA<22 participant 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 or available transportation (including provided Uber vouchers) to
drive them to and from study visits and for other transportation needs during the
treatment period.

- Has a significant other (someone who knows the participant well) that is appropriate
for doing the NPI assessment, 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.

Exclusion criteria:

- Known or suspected allergy to cannabinoids or excipients used in the study drug
formulation.

- Cannabis is detectable at the screening visit by blood testing or at the baseline
visit by urine testing. If cannabis is detected at either the screening or baseline
visit, then the participant is a screen fail and may return >14 days later for a
repeat screening visit. If cannabis is again detected at either the screening or
baseline visit, then the participant is excluded and not allowed to rescreen.

- History of drug or alcohol dependence; defined by prior inpatient stay(s) for this or
that patient states 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 (nicotinic acid) at =2000
mg/day or nicotinamide (nicotinic acid amide or nicotinamide) at =3000 mg/day,
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:

Hemoglobin < 10 g/dL WBC <3.0 x 109/L Neutrophils <1.5 x 109/L Lymphocytes < 0.5 x 109/L
Platelets <100 x 109/L Hemoglobin A1C > 9%

- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the
upper limit of normal. Persons with stable liver disease of known etiology can be
included, unless total bilirubin or prothrombin time/INR is abnormal.

- Is pregnant or lactating, or has a positive pregnancy test result pre-dose.

- If a sexually active female, is not surgically sterile or at least two years
post-menopausal, or does not agree to utilize an effective method of contraception
from screening through at least four weeks after the completion of study treatment,
using one of the following: barrier methods (diaphragm or partner using condoms plus
use of spermicidal jelly or foam, preferably double-barrier methods); oral or
implanted hormonal contraceptive; intrauterine device (IUD); or vasectomized male
partner.

- Planned elective surgery during study participation.



Age minimum: 40 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Intervention(s)

Other: Placebo

Drug: Cannabidiol

Primary Outcome(s)

Change in Movement Disorders Society-Unified Parkinson's disease rating scale (MDS-UPDRS) Part III (motor examination) scores [Time Frame: From baseline to the end of 2.5 mg/kg/day of CBD, through 3 weeks]

Secondary Outcome(s)

Change in Bradykinesia sub scores in MDS UPDRS [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in neurological exam [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Paced auditory serial addition test [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Parkinson's disease questionnaire (PDQ-39) [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Insomnia severity index [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Non-motor symptoms Scale for Parkinson's disease (NMSS) [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in RBDSQ [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Vital signs--weight [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Bulbar sub scores in MDS UPDRS [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Electrocardiograms [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Fatigue severity scale [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Home sleep monitoring (polysomnograph, PSG) [Time Frame: Home sleep monitoring will be measured only once, the day prior to 2.5 mg/kg/day assessment visit.]

Change in IRLS [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Judgment of line orientation [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Laboratory Values--chemistry [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Pittsburgh sleep quality index [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Physical exam [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Symbol digit modalities test [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Unified Dyskinesia Rating Scale [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Dermatology photography evaluation [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Controlled oral word association test [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Depression short form [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Dermatology Quality of Life Index [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Proportion of participants that discontinue the study due to study drug intolerance [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Frequency of study-related adverse events [Time Frame: Every 3-5 days at each dose level, assessed up to 3 weeks]

Change in semantic verbal fluency [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Smartphone-based timed UP&GO (TUG) [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in EuroQol-5 Dimension-5 level [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Hopkins verbal learning test [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Liver monitoring -- liver function impairment related adverse events [Time Frame: Baseline; at the end of 2.5 mg/kg/day; and every 3-5 days at each dose level, through 3 weeks.]

Change in Emotional and behavioral dyscontrol short form [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Neuropsychiatric Inventory (NPI) [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in The Columbia-Suicide Severity rating scale (C-SSRS) [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Grooved Pegboard Test [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Item 2.10 in MDS UPDRS [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Vital signs-Blood pressure (systolic and diastolic) [Time Frame: Baseline; at the end of 2.5 mg/kg/day, through 3 weeks]

Change in Impulsive-Compulsive disorders in Parkinson's disease rating scale (QUIP-RS) [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Item 3.15 and 3.16 in MDS UPDRS [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Montreal Cognitive Assessment (MoCA) [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Laboratory Values--hematology [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Pain Interference 4a short form [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in MDS-UPDRS [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Overactive bladder symptom score [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Total scores on items 3.17 and 3.18 in MDS-UPDRS [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Scales of Outcomes in Parkinson's disease (SCOPA) sleep [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Vital signs--respiratory rate [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Pain Intensity 3a short form [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Stanford Sleepiness Scale [Time Frame: Pre- and 3 hours post- dose at baseline visit]

Change in Wechsler test for Adult reading [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Vital signs--temperature [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Anxiety Short Form response [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Axial sub scores in MDS UPDRS [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Liver function monitoring --Liver function test [Time Frame: Baseline; at the end of 2.5 mg/kg/day; and every 3-5 days at each dose level, through 3 weeks.]

Change in Modified dysfunctional beliefs and attitudes about sleep questionnaire [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Rigidity sub scores in MDS UPDRS [Time Frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks]

Change in Vital signs-heart rate [Time Frame: Baseline; at the end of 2.5 mg/kg/day, through 3 weeks]

Secondary ID(s)

17-2318

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Colorado Department of Public Health and Environment