Clinical trial NCT00459420: Caffeine for Excessive Daytime Somnolence in Parkinson's Disease
Official title: Caffeine for Excessive Daytime Somnolence in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Parkinson's Disease
Excessive Daytime Somnolence
Keywords: Parkinson's disease
Excessive Daytime Somnolence
Caffeine
Disease-Modifying
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: University of Toronto
First posted: 2007-04-12
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Many patients with Parkinson's disease (PD) have sleep problems, including excessive sleepiness during the day. This is probably due to degeneration of sleep-regulating areas in the brain. At present, the only treatment for sleepiness in PD is modafinil, which is expensive and only partially effective. There is another potential treatment for sleepiness that is used worldwide, is inexpensive, well tolerated and safe - namely, caffeine. There have also been suggestions that caffeine may slow the progression of degeneration in PD, since coffee non-drinkers are at higher risk of developing PD. PD patients, even with severe sleepiness often do not use caffeine. It is unclear whether this is because their PD makes their sleepiness unresponsive to caffeine, because they cannot tolerate it, or whether this reflects their lifelong habit of non-use. This proposal outlines a trial in which patients with excessive sleepiness will be given caffeine or placebo (no therapy) in a blinded fashion. In this way, the effect of caffeine on sleepiness and motor symptoms can be directly analyzed. In addition, these findings can be used to test the tolerability of caffeine, to help plan a larger-scale study testing whether caffeine can slow the progression of PD

Detailed description: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by motor disability and many disabling non-motor symptoms. Excessive daytime somnolence (EDS) is found in up to 50% of patients with PD, and can cause considerable impairment of quality of life. At present, the only proven treatment for EDS in PD is modafinil, an alerting agent with an unknown mechanism of action. However, modafinil is only moderately effective and is very expensive. Caffeine is a very well tolerated and inexpensive alerting agent that is used worldwide, but very few patients with PD use it as therapy for EDS. It is unclear whether this is because it does not help EDS in PD, has side effects, or simply has not been considered because of lifelong patterns of non-use.

If caffeine can be demonstrated as an effective agent for EDS in PD, it will likely become the first-line agent for EDS. This will result in considerable cost savings for patients and health care payers, as well as potentially helping those who cannot tolerate, do not respond to, or cannot afford modafinil.

Another compelling question of interest to patients with PD is whether caffeine may be neuroprotective. Despite intensive research, no treatment has been found that can slow the progression of neurodegeneration in PD. Recently numerous epidemiologic studies have linked lifelong use of caffeine to a lower risk of PD. Although the mechanism for this finding is unclear, supporting evidence from animal models suggests that a true neuroprotective benefit of caffeine is a strong possibility. Alternatively, caffeine could have a benefit on motor manifestations of PD, which would prevent diagnosis of PD. Any finding of a symptomatic benefit of caffeine on motor manifestations of PD will have obvious and important implications for treatment of persons affected with PD and for planning of neuroprotective trials. Any finding of a neuroprotective benefit of caffeine will almost certainly result in its immediate widespread use in PD, with profound implications for patient care.

The present proposal is for a double blind randomized placebo controlled crossover trial that will answer three important questions in PD: is caffeine useful for the treatment of EDS in patients with PD? does caffeine have any symptomatic effect on the motor manifestations of PD? and, does caffeine have an acceptable tolerability and side effect profile that will allow planning of an eventual neuroprotective trial? Patients with PD who have EDS with an Epworth sleepiness scale of \>10 will be randomized to caffeine therapy (100 mg twice per day for three weeks, then 200 mg twice per day for three weeks) or placebo. A final assessment will be performed after a 4-week washout. A total of 52 patients will be randomized over a two-year period. The primary outcome measure will be the change in Epworth sleepiness scale between patients receiving caffeine versus placebo. Secondary outcome measures will include other sleep scales, tolerability measures, and measures of motor function and overall quality of life. After tests to assess normal distribution, analysis will be with two-sample t-test.

Eligibility criteria: Inclusion Criteria:

* A diagnosis of idiopathic PD
* Excessive daytime somnolence (defined as an Epworth sleepiness scale score of \>10).

Exclusion Criteria:

* Estimated daily caffeine intake of more than 200 mg per day
* Active peptic ulcer disease
* Supraventricular cardiac arrhythmia (such as atrial fibrillation or atrial flutter)
* Uncontrolled hypertension - defined as systolic bp \>170 or diastolic bp \>110 on two consecutive readings
* EDS is caused by sleep apnea, restless legs syndrome, narcolepsy, shift work, or sleep promoting agents.
* Current use of prescribed alerting agents such as modafinil and methylphenidate
* Pre-menopausal women who are not using effective methods of birth control
* Dementia, defined as MMSE \<24/30 and ADL impairment secondary to cognitive loss, or inability to understand consent process
* Depression, as defined by a Beck Depression Inventory score of \>15.
* Changes to antiparkinsonian medication in the last 3 months, or changes to antiparkinsonian medication are anticipated during the study protocol.

Primary outcomes:
measure: Change in Epworth Sleepiness Scale
timeFrame: 3 weeks
Secondary outcomes:
measure: Unified Parkinson Disease Rating Scale
timeFrame: 3 weeks
measure: Clinical Global Impression of Change
timeFrame: 3 weeks
measure: Pittsburgh Sleep Quality Index
timeFrame: 3 weeks
measure: Fatigue Severity Scale
timeFrame: 3 weeks
measure: Stanford Sleep Scale
timeFrame: 3 weeks
measure: PDQ-39
timeFrame: 3 weeks
measure: SF-36
timeFrame: 3 weeks
measure: Tolerability of Caffeine
timeFrame: 3 weeks
measure: Beck Depression Inventory
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
Study officials:
affiliation: Montreal General Hospital
name: Ron Postuma, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: