Parkinson's DiseasePhase 2NCT02818777
A Study of Tolerability and Efficacy of Cannabidiol on Tremor in Parkinson's Disease
A Phase 2 study testing cannabidiol in people with Parkinson's Disease, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- cannabidiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to Nov 2017
- 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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:
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado School of Medicine
Aurora, Colorado, 80045
About this study
Official title: A Randomized, Double Blind, Placebo-controlled Crossover Study of Tolerability and Efficacy of Cannabidiol (CBD) on Tremor in Parkinson's Disease
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.
Read the detailed description
Persons with Parkinson's disease (PD) have progressive disabling tremor, slowness, stiffness, balance impairment, cognitive deficits, psychiatric symptoms, autonomic dysfunction, fatigue and insomnia. Tremor may interfere with necessary daily and work functions. The disorder affects approximately seven million people globally. The total economic cost in the US is around 23 billion dollars. In addition to economic costs, PD reduces quality of life of those affected and their caregivers.
Cognitive impairment is a common feature and ranges from delayed recall in early stages to global dementia in up to 80% at end stage. PD with dementia has been associated with reduced quality of life, shortened survival, and increased caregiver distress.
Depression, anxiety and psychosis are also common and are particularly disabling in PD, even at the earliest stages. These symptoms have important consequences for quality of life and daily functioning, are associated with increased carer burden and risk for nursing home admission. Anxiety affects up to 40% of patients with PD, and may predate motor symptoms by several years. The most common anxiety disorders in PD are panic attacks (often during off-periods), generalized anxiety disorder, and simple and social phobias. Psychotic symptoms vary in frequency according to the definition used. If mild forms are included, these affect up to 50% of patients. Visual hallucinations are the most common type. However, hallucinations occur in all sensory domains and delusions of various types are also relatively common. The impact of psychosis is substantial in that it is associated with dementia, depression, earlier mortality, greater caregiver strain, and nursing home placement.
Current therapies are inadequate. Medications have improved the prognosis of PD, but also have problematic adverse effects. Since treatment of PD is often unsatisfactory and since marijuana has recently become legal and readily available in Colorado, persons with PD have been trying it. Patients have heard from the internet, support groups and other sources that marijuana is helpful. Most are doing so on their own, without the supervision or even knowledge of their neurologist. In a survey conducted in the spring of 2014 in University of Colorado Movement Disorders Center (UCMDC) clinic about 5% of 207 PD patients, average age 69, reported using marijuana. In the same clinic, about 30% of the PD patients have asked doctors during their visits over the past 6 months about marijuana. In another study Katerina Venderova and colleagues reported that 25% of PD patients had taken cannabis in the General University Hospital in Prague.
PD mostly affects the elderly, and with the cognitive, psychiatric and motor problems, subjects are prone to falls. Cannabis is well documented to cause psychosis, slowness, and incoordination. Studies have also shown that chronic users have structural and functional CNS alterations. Thus cannabis is expected to be risky in persons with PD. Further, there are many components of cannabis, and the cannabis preparations being sold in Colorado vary widely in composition. There are no definitive data regarding the benefits and risks of these various preparations in PD. Studies on safety and efficacy are greatly needed to protect this fragile Colorado population.
Cannabidiol (CBD) is a cannabinoid that is present to a lesser extent in street marijuana, and limits delta-9-tetrahydrocannabinol (THC)'s psychoactive effect. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and therefore has potential beneficial medical uses. Further, animal studies suggest that CBD is neuroprotective, perhaps due to reported anti-oxidative and anti-inflammatory actions.
Human trials report that CBD decreases anxiety and causes sedation in healthy individuals, decreases psychotic symptoms in schizophrenia and PD, and improves motor and non-motor symptoms and alleviates levodopa-induced dyskinesia in PD. The ratio of THC to CBD plays a role in the preparation's therapeutic outcome: strains of cannabis with higher concentrations of CBD did not produce short-term memory impairment vs. strains with higher concentrations of THC and lower concentrations of CBD.
Many clinicians who suspect cannabis may have a positive effective upon a particular patient group have no idea of the cannabinoid profile that is being used. Without knowing the composition, it is impossible to draw any conclusions simply because of the huge variety of strains utilised.
Given the current literature regarding CBD: possible neuroprotective effect, good tolerability, anxiolytic and antipsychotic effects and general lack of be well tolerated in PD, including its effect on tremor, the investigators hypothesize that CBD would be well tolerated and would reduce tremor, anxiety and psychosis, and would stabilize cognitive decline in PD. First the investigators will perform an open label study to determine a reasonable dose, and then a randomized, double-blind, placebo-controlled crossover study to evaluate the efficacy and tolerability of oral CBD on tremor and other important aspects of PD. A strength of the study is that it uses well defined form or CBD.
Stage 1: Open Label Dose Escalation Tolerability Study
Primary Specific Aim: To confirm that the dosage regimen of CBD, in the form of GWP42003-P recommended by the study drug manufacturer is safe and tolerated in 10 subjects with PD. GWP42003-P is started at 5 mg/kg/day and is increased by 5 mg/kg at 3 day intervals to a target dose of 25 mg/kg/day.
Secondary Specific Aim: To examine the effect of CBD on severity \& duration of tremor and other conditions that are problematic in PD.
The dose escalation tolerability study will be conducted in 10 subjects (the investigators will be recruiting up to 15 subjects to end up with 10) as an open label study lasting approximately 3 weeks followed by a 2-week safety follow up. Subjects are closely monitored as the dose is titrated. Subjects will have a screening visit, a baseline visit within the next three weeks, a visit when subjects are on 20 mg/kg/day, a final assessment visit when subjects have been on the maximal tolerated or the targeted dose for 10-15 days, and a safety visit 2 weeks later. The subject is to be on the maximal tolerated or targeted dose for 10-15 days. Subjects will be called on the 3rd day of each dose. During phone calls subjects are monitored for adverse events, especially excessive daytime sleepiness, symptoms of hepatotoxicity, as well as changes in medical history and concomitant medications. Subjects are also called 3 days after stopping the study drug to check for signs of withdrawal.
- Conditions
- Parkinson's Disease
- Being tested
- cannabidiol
- 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
- Medical subject headings
- Parkinson Disease, Tremor, Anxiety Disorders, Psychotic Disorders, Dyskinesias, Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cannabidiolDrug
Also called GWP42003-P
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: cannabidiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Baseline and 5 weeks
Number of Participants Had Changes in Physical Exam
A physical exam will be performed at each study visit.
Measured: Baseline and 5 weeks
Number of Participants Had Changes in EKG
EKG will be performed at each study visit.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Sum of items 3.17 and 3.18 of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) evaluates the rest tremor amplitude (3.17, score range 0-20) and constancy of rest tremor (3.18 score range 0-4). The sum scores of 3.17 and 3.18 range 0-24. Higher values represent a worse outcome.
Measured: Baseline and 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study startOct 2016
- Primary completionNov 2017
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Colorado Department of Public Health and Environment, GW Research Ltd
- Responsible party
- Sponsor
- Investigators
- Maureen A Leehey, M.D., Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02818777
- Sponsor's protocol ID
- 15-0929
- Status last verified
- Jan 2019
- First submitted
- 6 May 2016
- Last updated
- 19 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Placebo-controlled Crossover Study of Tolerability and Efficacy of Cannabidiol (CBD) on Tremor in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT02818777
- Acronym / sponsor ID
- 15-0929
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's Disease, Tremor, tolerability, safety, cognition, anxiety, psychosis, mood
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Colorado Department of Public Health and Environment, GW Research Ltd
- Study start
- Oct 2016 (actual)
- Primary completion
- Nov 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 30 Jun 2016 (estimated)
- Results
- Posted 19 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Persons with Parkinson's disease (PD) have progressive disabling tremor, slowness, stiffness, balance impairment, cognitive deficits, psychiatric symptoms, autonomic dysfunction, fatigue and insomnia. Tremor may interfere with necessary daily and work functions. The disorder affects approximately seven million people globally. The total economic cost in the US is around 23 billion dollars. In addition to economic costs, PD reduces quality of life of those affected and their caregivers.
Cognitive impairment is a common feature and ranges from delayed recall in early stages to global dementia in up to 80% at end stage. PD with dementia has been associated with reduced quality of life, shortened survival, and increased caregiver distress.
Depression, anxiety and psychosis are also common and are particularly disabling in PD, even at the earliest stages. These symptoms have important consequences for quality of life and daily functioning, are associated with increased carer burden and risk for nursing home admission. Anxiety affects up to 40% of patients with PD, and may predate motor symptoms by several years. The most common anxiety disorders in PD are panic attacks (often during off-periods), generalized anxiety disorder, and simple and social phobias. Psychotic symptoms vary in frequency according to the definition used. If mild forms are included, these affect up to 50% of patients. Visual hallucinations are the most common type. However, hallucinations occur in all sensory domains and delusions of various types are also relatively common. The impact of psychosis is substantial in that it is associated with dementia, depression, earlier mortality, greater caregiver strain, and nursing home placement.
Current therapies are inadequate. Medications have improved the prognosis of PD, but also have problematic adverse effects. Since treatment of PD is often unsatisfactory and since marijuana has recently become legal and readily available in Colorado, persons with PD have been trying it. Patients have heard from the internet, support groups and other sources that marijuana is helpful. Most are doing so on their own, without the supervision or even knowledge of their neurologist. In a survey conducted in the spring of 2014 in University of Colorado Movement Disorders Center (UCMDC) clinic about 5% of 207 PD patients, average age 69, reported using marijuana. In the same clinic, about 30% of the PD patients have asked doctors during their visits over the past 6 months about marijuana. In another study Katerina Venderova and colleagues reported that 25% of PD patients had taken cannabis in the General University Hospital in Prague.
PD mostly affects the elderly, and with the cognitive, psychiatric and motor problems, subjects are prone to falls. Cannabis is well documented to cause psychosis, slowness, and incoordination. Studies have also shown that chronic users have structural and functional CNS alterations. Thus cannabis is expected to be risky in persons with PD. Further, there are many components of cannabis, and the cannabis preparations being sold in Colorado vary widely in composition. There are no definitive data regarding the benefits and risks of these various preparations in PD. Studies on safety and efficacy are greatly needed to protect this fragile Colorado population.
Cannabidiol (CBD) is a cannabinoid that is present to a lesser extent in street marijuana, and limits delta-9-tetrahydrocannabinol (THC)'s psychoactive effect. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and therefore has potential beneficial medical uses. Further, animal studies suggest that CBD is neuroprotective, perhaps due to reported anti-oxidative and anti-inflammatory actions.
Human trials report that CBD decreases anxiety and causes sedation in healthy individuals, decreases psychotic symptoms in schizophrenia and PD, and improves motor and non-motor symptoms and alleviates levodopa-induced dyskinesia in PD. The ratio of THC to CBD plays a role in the preparation's therapeutic outcome: strains of cannabis with higher concentrations of CBD did not produce short-term memory impairment vs. strains with higher concentrations of THC and lower concentrations of CBD.
Many clinicians who suspect cannabis may have a positive effective upon a particular patient group have no idea of the cannabinoid profile that is being used. Without knowing the composition, it is impossible to draw any conclusions simply because of the huge variety of strains utilised.
Given the current literature regarding CBD: possible neuroprotective effect, good tolerability, anxiolytic and antipsychotic effects and general lack of be well tolerated in PD, including its effect on tremor, the investigators hypothesize that CBD would be well tolerated and would reduce tremor, anxiety and psychosis, and would stabilize cognitive decline in PD. First the investigators will perform an open label study to determine a reasonable dose, and then a randomized, double-blind, placebo-controlled crossover study to evaluate the efficacy and tolerability of oral CBD on tremor and other important aspects of PD. A strength of the study is that it uses well defined form or CBD.
Stage 1: Open Label Dose Escalation Tolerability Study
Primary Specific Aim: To confirm that the dosage regimen of CBD, in the form of GWP42003-P recommended by the study drug manufacturer is safe and tolerated in 10 subjects with PD. GWP42003-P is started at 5 mg/kg/day and is increased by 5 mg/kg at 3 day intervals to a target dose of 25 mg/kg/day.
Secondary Specific Aim: To examine the effect of CBD on severity \& duration of tremor and other conditions that are problematic in PD.
The dose escalation tolerability study will be conducted in 10 subjects (the investigators will be recruiting up to 15 subjects to end up with 10) as an open label study lasting approximately 3 weeks followed by a 2-week safety follow up. Subjects are closely monitored as the dose is titrated. Subjects will have a screening visit, a baseline visit within the next three weeks, a visit when subjects are on 20 mg/kg/day, a final assessment visit when subjects have been on the maximal tolerated or the targeted dose for 10-15 days, and a safety visit 2 weeks later. The subject is to be on the maximal tolerated or targeted dose for 10-15 days. Subjects will be called on the 3rd day of each dose. During phone calls subjects are monitored for adverse events, especially excessive daytime sleepiness, symptoms of hepatotoxicity, as well as changes in medical history and concomitant medications. Subjects are also called 3 days after stopping the study drug to check for signs of withdrawal.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cannabidiol | Experimental | Drug: cannabidiolGWP42003-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. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cannabidiolAlso: GWP42003-PPurified 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. | Drug | cannabidiol |
Primary outcome
Severity of Participants Reporting Study-related Adverse Events at Each Dose Level
Time frame: Every 3rd day on each dose level, assessed up to 5 weeks
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).
Number of Participants Had Changes in Orthostatic Blood Pressure
Time frame: Baseline and 5 weeks
Orthostatic blood pressure will be monitored at each study visit.
Number of Participants Had Changes in Physical Exam
Time frame: Baseline and 5 weeks
A physical exam will be performed at each study visit.
Number of Participants Had Changes in EKG
Time frame: Baseline and 5 weeks
EKG will be performed at each study visit.
Number of Participants Had Changes in Laboratory Values
Time frame: Baseline and 5 weeks
Laboratory tests (hematology, serum chemistry, and urinalysis) will be evaluated at each study visit.
Proportion of Subjects That Drop Out of the Study Due to Study Drug Intolerance
Time frame: Baseline and 5 weeks
Assessing the proportion of subjects that drop out of the study due to study drug intolerance.
Change in Movement Disorder Society-Unified Parkinsons Disease Rating Scale Total Score
Time frame: Baseline and 5 weeks
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.
Change in Montreal Cognitive Assessment (MoCA)
Time frame: Baseline and 5 weeks
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.
Change in Anxiety Short Form
Time frame: Baseline and 5 weeks
This includes 8 items that assess severity of anxiety. Scores range 8-40. Higher values represent a worse outcome.
Change in Neuropsychiatric Inventory (NPI)
Time frame: Baseline and 5 weeks
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.
Change in Depression Short Form
Time frame: Baseline and 5 weeks
This includes 8 items that assess severity of depression. Score range 8-40. Higher values represent a worse outcome.
Change in Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep-night Time Sleep
Time frame: Baseline and 5 weeks
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.
Change From Baseline of REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)
Time frame: Baseline and 5 weeks
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.
Change in Emotional and Behavioral Dyscontrol Short Form
Time frame: Baseline and 5 weeks
8 items that assess severity of emotional and behavioral dyscontrol. Scores range 8-40. Higher values represent a worse outcome.
Change in Pain Severity Form
Time frame: Baseline and 5 weeks
This will assess severity of pain. Scores range 3-15. Higher scores represent a worse outcome.
Change in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
Time frame: Baseline and 5 weeks
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.
Change in Fatigue Severity Scale
Time frame: Baseline and 5 weeks
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.
Change in International Restless Legs Syndrome Study Group Rating Scale for Restless
Time frame: Baseline and 5 weeks
This encompasses a ten-question instrument for measuring severity of restless legs syndrome (RLS). Score range 0-40. Higher values represent a worse outcome.
Change in Unified Dyskinesia Rating Scale (UDysRS)
Time frame: Baseline and 5 weeks
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.
1 secondary outcome
Change in MDS-UPDRS Tremor Score (Total of Items 3.17 and 3.18) in the ON State
Time frame: Baseline and 5 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maureen A Leehey, M.D. principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cannabidiol in people with Parkinson's Disease, run by University of Colorado, Denver at 1 site in United States.
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 9 inclusion and 7 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 19 Feb 2019. 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 United States. 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. 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 19 Feb 2019). 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?
Severity of Participants Reporting Study-related Adverse Events at Each Dose Level (time frame: Every 3rd day on each dose level, assessed up to 5 weeks). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Feb 2019.