Caffeine for Motor Manifestations of Parkinson's Disease

NCT01190735 | Completed Phase 2

• 1 other identifier: CIHR-219243
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease

Keywords

Caffeine; Parkinson's Disease; Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Caffeine citrate; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Central Nervous System Stimulants; Physiological Effects of Drugs; Central Nervous System Agents; Therapeutic Uses

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (10)

• Epworth Sleepiness Scale (ESS)

  6 weeks

• Unified Parkinson Disease Rating Scale(UPDRS): Part II

  6 weeks

• Timed Up and Go (TUG)

  6 weeks

• Clinical Global Impression of Change

  6 weeks

• Pittsburgh Sleep Quality Index

  6 weeks

Study Arms (1)

Caffeine

EXPERIMENTAL

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.

Drug: Caffeine alkaloid

Interventions

Caffeine alkaloid 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.

Also known as: Wake-Ups, 100mg tabs, NPN 00533629, serial no 5503701103, 200mg tabs, NPN, 80003474, serial no 5503701105

Caffeine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Estimated daily caffeine intake of more than 200 mg per day.
• Subject has dementia (MMSE \< 26/30) and ADL impairment secondary to cognitive loss, inability to understand consent process.
• Changes to antiparkinsonian medications in last 4 weeks or changes will be required during the period of the study protocol.
• Contraindication to caffeine use:
• Uncontrolled hypertension (systolic bp \>170 or diastolic bp \>110 on two consecutive readings)
• Use of lithium or clozapine
• Pre-menopausal women who are not using effective methods of birth control
• Current use of prescribed alerting agents such as modafinil and methylphenidate
• Active peptic ulcer disease
• Supraventricular cardiac arrhythmia
• 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.

Sponsors & Collaborators

• Ron Postuma: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Related Links

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

MeSH Terms

Conditions

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Synucleinopathies

Study Officials

• Ron Postuma, MD, Msc

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

  STUDY DIRECTOR

• Robert Altman, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: August 26, 2010
• First Posted: August 30, 2010
• Study Start: August 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: April 16, 2015

Record last verified: 2015-04

Locations

CA (1)