Text Size

Caffeine as a Therapy for Parkinson's Disease

This study is not yet open for participant recruitment.
Verified November 2012 by McGill University Health Center
Sponsor:
Collaborator:
Parana Parkinson Association Pontifical Catholic University of Parana
Information provided by (Responsible Party):
Ron Postuma, McGill University Health Center
ClinicalTrials.gov Identifier:
NCT01738178
First received: November 28, 2012
Last updated: November 29, 2012
Last verified: November 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
 Drug: Caffeine
Drug: Placebo
 Phase 3

Study Type: Interventional
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by McGill University Health Center:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • MDS-UPDRS components and subscales - each individual component will be assessed, including: [ Time Frame: every 6 months ] [ Designated as safety issue: No ]
    1. 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
    2. 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.
    3. motor complications - motor fluctuations and dyskinesia
    4. 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

    1. the SCOPA-sleep8 nighttime scale.
    2. the SCOPA-sleep8 daytime scale
    3. 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).


Estimated Enrollment: 250
Study Start Date: February 2013
Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control - Placebo
These participants will receive placebo tablets during the first 5 years
 Drug: Placebo
Active Comparator: Caffeine group
This group of participants will receive caffeine tablets.
 Drug: Caffeine

  Eligibility

Ages Eligible for Study:   45 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All patients must have idiopathic PD diagnosed as parkinsonism according to the UK brain bank criteria, and PD considered the likeliest underlying cause according to the treating physician. Other inclusion criteria include:

  1. PD diagnosis: between 6 months and 6 years
  2. Hoehn and Yahr stage I-III
  3. Age at least 45 and less than 75 (to optimize survival over the 5-year trial).
  4. Receiving symptomatic therapy for PD for at least 6 months. Dose must have been stable over the previous 3 months.

Exclusion Criteria:

  1. Caffeine intake >150 mg per day (i.e. more than one cup of filtered coffee per day) or prescribed adenosine antagonists - caffeine intake will be measured by a standardized intake questionnaire. Intake will be converted into estimated caffeine mg dose by standard caffeine-content charts.
  2. Active peptic ulcer disease, or symptomatic gastroesophageal reflux disease.
  3. Supraventricular cardiac arrhythmia (such as atrial fibrillation or atrial flutter) - Electrocardiogram will be measured at baseline to rule out supraventricular tachycardia.
  4. Uncontrolled hypertension - systolic bp >170 or diastolic bp >110 on two readings.
  5. Pre-menopausal women who are not using effective methods of birth control
  6. Cognitive impairment, defined as MoCA <23/30.
  7. Moderate-Severe Depression, as defined by a Beck Depression Inventory score of >19.
  8. Changes to antiparkinsonian medication in the last 3 months, or changes to antiparkinsonian medication are anticipated during the next six months.
  9. Current use of lithium or clozapine (pharmacokinetic interactions).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01738178

Contacts
Contact: Ronald B Postuma, Md, MSc 514-934-8026 ron.postuma@mcgill.ca

Locations
Brazil
Parana Parkinson Association - Pontifical Catholic University of Parana Not yet recruiting
Curitiba, PR, Brazil, 80240-021
Contact: Renato Puppi Munhoz, MD     5541.99970696     renatopuppi@yahoo.com    
Principal Investigator: Renato Puppi Munhoz, MD            
Canada, Quebec
McGill University Health Center Not yet recruiting
Montreal, Quebec, Canada, H3G 1A4
Contact: Ron Postuma, MD, MSc     514-934-8026     ron.postuma@mcgill.ca    
Sponsors and Collaborators
McGill University Health Center
Parana Parkinson Association Pontifical Catholic University of Parana
Investigators
Principal Investigator: Ronald B Postuma, MD, MSc Research Insitute of the MUHC
  More Information

No publications provided

Responsible Party: Ron Postuma, Neurologist, McGill University Health Center
ClinicalTrials.gov Identifier: NCT01738178     History of Changes
Other Study ID Numbers: 2778
Study First Received: November 28, 2012
Last Updated: November 29, 2012
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Caffeine
Central Nervous System Stimulants
Physiological Effects of Drugs
 Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on May 16, 2013