Caffeine as a Therapy for Parkinson's Disease
Parkinson's disease is a common neurodegenerative disorder in which patients experience progressive motor disability and many disabling non-motor symptoms. Recent studies have consistently found that people who do not use caffeine are at higher risk of developing Parkinson's disease. This suggests that caffeine may have potential as a treatment for PD.
In a pilot study of caffeine for daytime sleepiness in PD, there was evident benefit on the motor manifestations of disease. There have been other lines of evidence that have suggested caffeine could be useful in PD. This study is to evaluate the efficacy of caffeine 200 mg BID vs matching placebo for motor and non-motor aspects of disease. This will be in three stages. In the first six-month stage, medications will be held constant, to see whether caffeine does have motor benefits. Then we will perform a four-year extension stage to define if the effects of caffeine persist (or even magnify), and to see if caffeine helps reduce dose of other PD meds and/or prevents their side effects. Finally, we will finish with a six-month stage in which we will place all patients on caffeine - this will allow us to assess caffeine's use in later disease, but more importantly, will assess whether early use of caffeine produces long term changes beyond its immediate effects.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Caffeine as a Therapeutic Agent in Parkinson's Disease|
- Motor manifestations associated with Parkinson's disease [ Time Frame: every 6 months ] [ Designated as safety issue: No ]For each stage of the study, the MDS-Unified Parkinson Disease Rating Scale (MDS-UPDRS)will be used as the primary outcome. The MDS-UPDRS is the standard scale used for grading severity of PD - its revised 2008 version has more standardized motor assessment, better sensitivity to change in early-mid stages, and a broader assessment of non-motor PD. It starts with a patient self-administered questionnaire covering activities of daily living, motor symptoms, and non-motor domains. There is then a scored clinical interview assessing cognitive and psychiatric symptoms and motor complications. The Hoehn and Yahr scale (5-point overall disease severity index) is included3. Finally, there is a formal examination component (Part III) (performed in the medication 'on' state for this study).
- MDS-UPDRS components and subscales - each individual component will be assessed, including: [ Time Frame: every 6 months ] [ Designated as safety issue: No ]
- motor symptoms, according to each subscale question. These include speech deficits, swallowing dysfunction, motor activities of daily living (dressing, feeding, turns in bed, etc), tremor, gait slowing, freezing, and falls
- non-motor symptoms, according to each subscale question. These include constipation, urinary dysfunction, sexual dysfunction, orthostatic symptoms, depression, anxiety, cognitive symptoms, apathy, somnolence, insomnia, pain, and fatigue.
- motor complications - motor fluctuations and dyskinesia
- Hoehn and Yahr staging (a five-point global staging system for PD).
- Cognition [ Time Frame: every 6 months ] [ Designated as safety issue: No ]Although cognitive symptoms are addressed with the UPRDS, we will include two objective measures, the Montreal Cognitive Assessment (MoCA), and Mini-mental State Examination. The MoCA is a brief cognitive test, which is used extensively in PD. The MMSE will be used in diagnosis of dementia. Dementia will be assessed according to Level I MDS criteria. ADL impairment due to cognitive loss will be documented according to MDS criteria.
- Sleep [ Time Frame: every 6 motnhs ] [ Designated as safety issue: No ]
Because caffeine may have special effectiveness for sleep disorders, we will include additional sleep questionnaires, including
- the SCOPA-sleep8 nighttime scale.
- the SCOPA-sleep8 daytime scale
- the REM sleep behavior disorder single-question screen (RBD1Q)
- Quality of life [ Time Frame: every 6 months ] [ Designated as safety issue: No ]The Parkinson's Disease Questionnaire-8 is a quality of life index for PD with 8 self-administered items assessing motor function, gait, mood, cognition, etc.
- Medication utilization [ Time Frame: evry 6 months ] [ Designated as safety issue: Yes ]To assess caffeine's potential medication-sparing benefit, we will quantify all medications at each visit. Levodopa-dose equivalents will be calculated with standard criteria. Total medication cost will be calculated using current Canadian pharmacy pricing.
- Tolerability and side effects of caffeine [ Time Frame: every 6 motnhs ] [ Designated as safety issue: Yes ]A structured questionnaire will screen for irritability, symptoms of gastrointestinal reflux, diarrhea, sleepiness, palpitations, sweating, and tremulousness. In addition, open-ended questions will allow reporting of other side effects. Blood pressure will be measured at each visit to exclude new-onset hypertension, and orthostatic hypotension will be objective assessed with blood pressure measurements lying and standing (1 minute).
|Study Start Date:||February 2013|
|Estimated Primary Completion Date:||February 2021 (Final data collection date for primary outcome measure)|
Placebo Comparator: Control - Placebo
These participants will receive placebo tablets during the first 5 years
Active Comparator: Caffeine group
This group of participants will receive caffeine tablets.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01738178
|Contact: Ronald B Postuma, Md, MScfirstname.lastname@example.org|
|Parana Parkinson Association - Pontifical Catholic University of Parana||Not yet recruiting|
|Curitiba, PR, Brazil, 80240-021|
|Contact: Renato Puppi Munhoz, MD 5541.99970696 email@example.com|
|Principal Investigator: Renato Puppi Munhoz, MD|
|McGill University Health Center||Not yet recruiting|
|Montreal, Quebec, Canada, H3G 1A4|
|Contact: Ron Postuma, MD, MSc 514-934-8026 firstname.lastname@example.org|
|Principal Investigator:||Ronald B Postuma, MD, MSc||Research Insitute of the MUHC|