A Study of Tolerability and Efficacy of Cannabidiol on Motor Symptoms in Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      The major purpose of this study is to assess the efficacy of CBD on motor symptoms of
      Parkinson's Disease (PD), and secondarily to study the safety and tolerability of CBD and
      other efficacy, particularly regarding tremor in PD. The study has been powered to detect a
      clinically significant reduction in Movement Disorder Society (MDS) Unified Parkinson's
      Disease Rating Scale (UPDRS) Part III motor scores. This is a 1:1 parallel, double-blind,
      randomized controlled trial (RCT) with 60 participants. The investigators will be recruiting
      up to 75 participants; the goal is to have 60 participants (30 in CBD group and 30 in placebo
      group) complete the study. The study drug is obtained from the National Institute on Drug
      Abuse (NIDA).
    

Detailed description: 
      Persons with 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. Community-based
      studies have estimated the point prevalence for dementia in PD to be 28% and 44%.

      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. Thus, it is crucial to treat these symptoms in order to optimize the management of
      PD patients.

      Generally, however, 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 cannabis 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 Hospital Movement Disorders clinic
      about 5% of 207 PD patients, average age 69, reported using cannabis. In another study
      Katerina Venderova and colleagues reported that 25% of PD patients had taken cannabis in the
      General University Hospital in Prague. In the investigators clinics, about 30% of the PD
      patients have asked doctors during their clinic visits over the past 6 months about cannabis.
      In an anonymous web-based survey, 72% PD patients reported current or past using medical
      cannabis, and 48% reducing prescription medication since beginning cannabis use.

      PD mostly affects the elderly, and affected persons often have cognitive, psychiatric and
      motor problems, such as being prone to falling. Cannabis is well documented to cause
      psychosis, anxiety, slowness and incoordination. Studies have also shown that chronic users
      have structural and functional Central Nervous System (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 in of these various preparations in PD.
      Studies on safety and efficacy are greatly needed to protect this fragile Colorado
      population.

      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. Given the current literature
      regarding CBD: possible neuroprotective effect, good tolerability, anxiolytic and
      antipsychotic effects and general lack of information in PD, including its effect on tremor,
      the investigators feel that it is important to study its use in PD further. The investigators
      hypothesized that it would reduce tremor, anxiety and psychosis, and would be well tolerated
      in PD.

      The Specific Aims are:

      Primary Specific Aim: To evaluate the efficacy of CBD on motor symptoms in PD, specifically
      on the motor section of the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS).

      Secondary Specific Aim: To assess the safety and tolerability of CBD in PD, and to examine
      the effect of CBD on severity & duration of intractable tremor, night-time sleep, rigidity,
      emotional dyscontrol, anxiety and pain in PD.

      Exploratory Analyses:

      To study the efficacy of CBD on cognition, psychosis, sleep, daytime sleepiness, mood,
      fatigue, impulsivity, bladder function, other motor and non-motor PD signs, restless legs
      syndrome and Rapid Eye Movement (REM) sleep behavior disorder and quality of life.

      The study is a randomized, placebo controlled, double-blind parallel design with two
      treatment arms, each of approximately 2-3 weeks duration. In the 2-3 week treatment phase
      participants will start study drug and titrate up to the maximum tolerated or targeted dose
      (2.5 mg/kg/day of CBD). Each participant will have a screening visit, baseline visit within 3
      weeks, 1 liver function monitoring visits on 3rd to 5th day of 2.5 mg/kg/day, 2 dose
      assessment visit (1.25 mg/kg/day and 2.5 mg/kg/day), and a safety visit (6 visits total).
      Participants will be evaluated on the 3rd to 5th day at each dose level for monitoring liver
      function and adverse events, as well as changes in medical history and concomitant
      medications. Participants are called 3 days and 1 week after stopping the study drug to check
      for signs of withdrawal.
    

Intervention name(s): Cannabidiol; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution; Subjects randomized to this arm will receive Placebo
Other intervention name(s): CBD
Intervention MeSH terms: Cannabidiol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Parkinson's Disease; Motor symptoms; Tremor; tolerability; safety; cognition; anxiety; psychosis; mood; dyskinesia; sleep; cannabidiol; cannabis; efficacy; non-motor symptoms; quality of life; seborrhea