Caffeine for Motor Manifestations of Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

Caffeine for Motor Manifestations of Parkinson's Disease: An Open-Label Dose-Response Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01190735
• Other study ID #: CIHR-219243
• Status: Completed
• Phase: Phase 2
• First received: August 26, 2010
• Last updated: April 15, 2015
• Start date: August 2010
• Est. completion date: February 2011

Study information

• Verified date: April 2015
• Source: McGill University Health Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Canada	Montreal General Hospital	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Ron Postuma	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerability	Patients will be given a structured questionnaire targeting common side effects of caffeine, as well as a series of open-ended questions for other side effects. Vital signs will be measured. Questionnaire symptoms will be selected, where available, from the common terminology criteria for adverse events, version 3.0, developed by the National Cancer Institute. A severity of 2 or greater on the 5-point scale will delineate a dose-limiting effect. Evaluations will occur in person after 2 weeks, 4 weeks, 6 weeks (at study termination) and via telephone follow-up at the end of weeks 1,3 and 5.	6 weeks	Yes
Secondary	Epworth Sleepiness Scale (ESS)	Will systematically track changes in ESS.	6 weeks	No
Secondary	Unified Parkinson Disease Rating Scale(UPDRS): Part II	Systematically performing part II of the UPDRS, motor examination.	6 weeks	No
Secondary	Timed Up and Go (TUG)	This is a measure of gait and transfer speed.	6 weeks	No
Secondary	Clinical Global Impression of Change		6 weeks	No
Secondary	Pittsburgh Sleep Quality Index		6 weeks	No
Secondary	Fatigue Severity Scale		6 weeks	No
Secondary	The Parkinson's Disease Questionnaire - PDQ-39	This self-completion questionnaire addresses aspects of functioning and well-being in those affected by Parkinson's Disease (PD). Considered to be the industry 'gold standard' in the assessment of quality of life in PD patients. The 39-point PDQ provides scores on 8 scales: mobility, activities of daily living, emotions, stigma, social support, cognition, communications and bodily discomfort.	6 weeks	No
Secondary	Beck Depression Inventory	Self-administered questionnaire.	6 weeks	No
Secondary	Beck Anxiety Inventory	Self-administered questionnaire.	6 weeks	No
Secondary	UPDRS: Part I,II,IV	Systematically querying I (non-motor aspects of activities of daily living), II (motor aspects of activities of daily living) and IV (motor complications)	6 weeks	No

External Links

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