Caffeine for Excessive Daytime Somnolence in Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

Caffeine for Excessive Daytime Somnolence in Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00459420
• Other study ID #: GEN-06-68
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: April 11, 2007
• Last updated: April 15, 2015
• Start date: April 2007
• Est. completion date: July 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

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Excessive Daytime Somnolence
• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Caffeine 100-200 mg BID
Caffeine 100 mg BID for three weeks, then 200 mg BID for three weeks, then 100 mg BID for 1 week, then placebo
• placebo
placebo

Locations

Country	Name	City	State
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Toronto Western Hospital	Toronto	Ontario

Sponsors (3)

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

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Epworth Sleepiness Scale		3 weeks	No
Secondary	Unified Parkinson Disease Rating Scale		3 weeks	No
Secondary	Clinical Global Impression of Change		3 weeks	No
Secondary	Pittsburgh Sleep Quality Index		3 weeks	Yes
Secondary	Fatigue Severity Scale		3 weeks	No
Secondary	Stanford Sleep Scale		3 weeks	Yes
Secondary	PDQ-39		3 weeks	No
Secondary	SF-36		3 weeks	No
Secondary	Tolerability of Caffeine		3 weeks	Yes
Secondary	Beck Depression Inventory		3 weeks	Yes