Caffeine for Motor Manifestations of Parkinson's Disease

NCT ID: NCT01190735

Last Updated: 2015-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2011-02-28

Brief Summary

Numerous epidemiological studies have linked lifelong use of caffeine to a lower risk of Parkinson's disease (PD) - prospective studies have estimated that non-coffee drinkers have an approximately 1.7-2.5 fold increased risk of developing PD compared to coffee drinkers. This is an extremely important finding which deserves further more in depth investigations.

The exact pathophysiological mechanism remains elusive, but multiple hypotheses do exist: Caffeine antagonizes adenosine receptors directly yielding an improvement on motor systems and even on Levodopa serum concentrations (when on therapy). An additional explanation is that adenosine antagonism has neuroprotective properties by acting locally on basal ganglia circuits and the substantia nigra.

The current study aims to identify the optimal caffeine dose with maximal motor benefit and the least amount of undesirable adverse effects.

Detailed Description

Caffeine has been in widespread use for centuries, and is the commonest psychostimulant used worldwide. In Canada, estimates of mean daily intake for a 70 kg person range from 200-450 mg. The main sources of caffeine ingestion are in beverages - depending on brewing technique a typical cup of drip-filtered coffee can contain between 100 and 150 mg of caffeine (gourmet drip coffees contain up to 300 mg and espresso preparations generally contain much less caffeine). Black tea contains between 30 and 50 mg, and lower amounts of caffeine are found in soft drinks, green teas, and chocolate. Caffeine is a substance with a well-defined effect and side-effect profile, and in general it is very well tolerated. Side effects can include irritability, insomnia, enhancement of physiologic tremor, and stomach upset. Abrupt withdrawal from caffeine can cause headache and excessive sleepiness. Caffeine can exacerbate pre-existing supraventricular tachycardia. Multiple large-scale epidemiologic studies have not found evidence for adverse health effects with long-term moderate use of caffeine. Caffeine has a T-max of approximately 1 hour and readily crosses the blood brain barrier. It has first order kinetics. Plasma half life estimates range from 3-6 hours, increased in the case of pregnancy or severe liver disease. Drug interactions are uncommon: Caffeine withdrawal may cause lithium toxicity, and caffeine increases clozapine levels.

CNS effects of caffeine are mainly due to antagonism of the A1 and A2A adenosine receptors, (A2A predominates in the striatum). Potential effects upon motor manifestations of PD are predominantly related to the antagonistic action of adenosine on dopamine release in the striatum. Partial tolerance to CNS effects is common, and begins to occur within one week (tolerance is more pronounced for the A1 receptor, suggesting that motor changes may show less tolerance). If effective for PD, caffeine has the potential to be a very important advance for patient care, for numerous reasons. First of all, it has been in widespread use for centuries, so the long-term safety has been determined. Caffeine is widely available as tablets which are very inexpensive (i.e. less than 25 cents per tablet), potentially resulting in substantial cost savings for patients and health-care planners. Caffeine also has the potential (as yet unproven) to treat non-motor manifestations of PD, particularly excessive daytime somnolence.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Caffeine

Each patient will take pills twice per day containing 100-200 mg of caffeine (as synthetic caffeine alkaloid). Patients will be instructed to take whatever caffeine-containing beverages they are accustomed to taking, without changing their habitual schedule (note that all will be taking \<200 mg per day). Caffeine intake will be assessed at each visit. Patients will continue their usual PD medications, without change in dose or timing for the entire duration of the study. Medication will be provided in pre-packaged dosettes.

Group Type: EXPERIMENTAL

Caffeine alkaloid

Intervention Type: DRUG

The following intervention will be provided for six consecutive weeks:

Week 1 (100 mg BID), Week 2 (200 mg BID), Week 3 (300 mg BID), Week 4 (400 mg BID), Week 5 and 6(500 mg BID). At the conclusion of the study, patients will decrease their dose by 100 mg BID every other day, until caffeine is stopped. This gradual reduction will be to prevent withdrawal symptoms. If a patient experiences a dose-limiting event, they will be terminated from the study, and will withdraw from the medication in the same manner. If dose-limiting events occur between visits, patients will be encouraged to decrease the caffeine dose back to the previously-tolerated dose until in-person assessment can be performed.

Interventions

Caffeine alkaloid

The following intervention will be provided for six consecutive weeks:

Week 1 (100 mg BID), Week 2 (200 mg BID), Week 3 (300 mg BID), Week 4 (400 mg BID), Week 5 and 6(500 mg BID). At the conclusion of the study, patients will decrease their dose by 100 mg BID every other day, until caffeine is stopped. This gradual reduction will be to prevent withdrawal symptoms. If a patient experiences a dose-limiting event, they will be terminated from the study, and will withdraw from the medication in the same manner. If dose-limiting events occur between visits, patients will be encouraged to decrease the caffeine dose back to the previously-tolerated dose until in-person assessment can be performed.

Intervention Type: DRUG

Other Intervention Names

Wake-Ups; 100mg tabs, NPN 00533629, serial no 5503701103; 200mg tabs, NPN, 80003474, serial no 5503701105

Eligibility Criteria

Inclusion Criteria

1. Subject has been diagnosed with idiopathic Parkinson's disease (stage I - IV Hoehn and Yahr)

Exclusion Criteria

1. Estimated daily caffeine intake of more than 200 mg per day.

2. Subject has dementia (MMSE < 26/30) and ADL impairment secondary to cognitive loss, inability to understand consent process.

3. Changes to antiparkinsonian medications in last 4 weeks or changes will be required during the period of the study protocol.

4. Contraindication to caffeine use:

1. Uncontrolled hypertension (systolic bp >170 or diastolic bp >110 on two consecutive readings)

2. Use of lithium or clozapine

3. Pre-menopausal women who are not using effective methods of birth control

4. Current use of prescribed alerting agents such as modafinil and methylphenidate

5. Active peptic ulcer disease

6. Supraventricular cardiac arrhythmia

7. Previous adverse reaction to caffeine which either required admission to hospital,or after which the patient was directly advised by a physician to not use caffeine.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Ron Postuma

OTHER

Sponsor Role: lead

Responsible Party

Ron Postuma

Neurologist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ron Postuma, MD, Msc

Role: STUDY_DIRECTOR

McGill University Health Centre/Research Institute of the McGill University Health Centre

Robert Altman, MD

Role: PRINCIPAL_INVESTIGATOR

McGill University Health Centre/Research Institute of the McGill University Health Centre

Locations

Montreal General Hospital

Montreal, Quebec, Canada

Countries

Canada

Related Links

http://clinicaltrials.gov/ct2/show/NCT00459420?term=postuma&rank=1

Ongoing study investigating caffeine for excessive daytime somnolence in Parkinson's Disease

Other Identifiers

CIHR-219243

Identifier Type: -

Identifier Source: org_study_id