Caffeine for Motor Manifestations of Parkinson's Disease

This study has been completed.
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by:
McGill University Health Center
ClinicalTrials.gov Identifier:
NCT01190735
First received: August 26, 2010
Last updated: July 19, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
Drug: Caffeine alkaloid
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Caffeine for Motor Manifestations of Parkinson's Disease: An Open-Label Dose-Response Study.

Resource links provided by NLM:


Further study details as provided by McGill University Health Center:

Primary Outcome Measures:
  • Tolerability [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Epworth Sleepiness Scale (ESS) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Will systematically track changes in ESS.

  • Unified Parkinson Disease Rating Scale(UPDRS): Part II [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Systematically performing part II of the UPDRS, motor examination.

  • Timed Up and Go (TUG) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    This is a measure of gait and transfer speed.

  • Clinical Global Impression of Change [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Pittsburgh Sleep Quality Index [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Fatigue Severity Scale [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • The Parkinson's Disease Questionnaire - PDQ-39 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    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.

  • Beck Depression Inventory [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Self-administered questionnaire.

  • Beck Anxiety Inventory [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Self-administered questionnaire.

  • UPDRS: Part I,II,IV [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Systematically querying I (non-motor aspects of activities of daily living), II (motor aspects of activities of daily living) and IV (motor complications)


Estimated Enrollment: 28
Study Start Date: August 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Caffeine
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

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.

Other Names:
  • Wake-Ups
  • 100mg tabs, NPN 00533629, serial no 5503701103
  • 200mg tabs, NPN, 80003474, serial no 5503701105

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01190735

Locations
Canada, Quebec
Montreal General Hospital
Montreal, Quebec, Canada, H3G 1A4
Sponsors and Collaborators
McGill University Health Center
Canadian Institutes of Health Research (CIHR)
Investigators
Study Director: Ron Postuma, MD, Msc McGill University Health Center
Principal Investigator: Robert Altman, MD McGill University Health Center
  More Information

Additional Information:
No publications provided

Responsible Party: Ron Postuma, Montreal General Hospital
ClinicalTrials.gov Identifier: NCT01190735     History of Changes
Other Study ID Numbers: CIHR-219243
Study First Received: August 26, 2010
Last Updated: July 19, 2011
Health Authority: Canada: Health Canada

Keywords provided by McGill University Health Center:
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

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Central Nervous System Stimulants
Caffeine
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on August 01, 2014