Caffeine for Excessive Daytime Somnolence in Parkinson's Disease
Information source: McGill University Health Center
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Parkinson's Disease; Excessive Daytime Somnolence
Intervention: Caffeine 100-200 mg BID (Drug); placebo (Drug)
Phase: Phase 2/Phase 3
Status: Completed
Sponsored by: Ron Postuma Official(s) and/or principal investigator(s): Ron Postuma, MD, MSc, Principal Investigator, Affiliation: Montreal General Hospital
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
Clinical Details
Official title: Caffeine for Excessive Daytime Somnolence in Parkinson's Disease
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Change in Epworth Sleepiness Scale
Secondary outcome: Unified Parkinson Disease Rating ScaleClinical Global Impression of Change Pittsburgh Sleep Quality Index Fatigue Severity Scale Stanford Sleep Scale PDQ-39 SF-36 Tolerability of Caffeine Beck Depression Inventory
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Toronto Western Hospital, Toronto, Ontario, Canada
Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada
Additional Information
Starting date: April 2007
Last updated: April 15, 2015
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