A Randomized, Double Blind, Placebo-controlled Crossover Study of Tolerability and Efficacy of Cannabidiol (CBD) on Tremor in Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Number of Participants Had Changes in Orthostatic Blood Pressure
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
cannabidiol
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.
干预措施: cannabidiol (Drug)
结局指标
主要结局
Number of Participants Had Changes in Orthostatic Blood Pressure
时间窗: Baseline and 5 weeks
Orthostatic blood pressure will be monitored at each study visit.
Proportion of Subjects That Drop Out of the Study Due to Study Drug Intolerance
时间窗: Baseline and 5 weeks
Assessing the proportion of subjects that drop out of the study due to study drug intolerance.
Change in Anxiety Short Form
时间窗: 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 Depression Short Form
时间窗: 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 Pain Severity Form
时间窗: Baseline and 5 weeks
This will assess severity of pain. Scores range 3-15. Higher scores represent a worse outcome.
Number of Participants Had Changes in EKG
时间窗: Baseline and 5 weeks
EKG will be performed at each study visit.
Change in Emotional and Behavioral Dyscontrol Short Form
时间窗: 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 International Restless Legs Syndrome Study Group Rating Scale for Restless
时间窗: 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.
Severity of Participants Reporting Study-related Adverse Events at Each Dose Level
时间窗: 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 Physical Exam
时间窗: Baseline and 5 weeks
A physical exam will be performed at each study visit.
Number of Participants Had Changes in Laboratory Values
时间窗: Baseline and 5 weeks
Laboratory tests (hematology, serum chemistry, and urinalysis) will be evaluated at each study visit.
Change in Neuropsychiatric Inventory (NPI)
时间窗: 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 Movement Disorder Society-Unified Parkinsons Disease Rating Scale Total Score
时间窗: 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)
时间窗: 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 Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep-night Time Sleep
时间窗: 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 in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
时间窗: 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
时间窗: 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 Unified Dyskinesia Rating Scale (UDysRS)
时间窗: 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.
Change From Baseline of REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ)
时间窗: 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.
次要结局
- Change in MDS-UPDRS Tremor Score (Total of Items 3.17 and 3.18) in the ON State(Baseline and 5 weeks)