Clinical trial NCT01738178: Caffeine as a Therapy for Parkinson's Disease
Official title: Caffeine as a Therapeutic Agent in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: Pontifícia Universidade Católica do Paraná
name: University of Calgary
name: University of Newfoundland and Eastern Health
name: University Health Network, Toronto
name: UBC Hospital
name: Movement Disorder Clinic - Deer Lodge Centre
name: The Ottawa Hospital
First posted: 2012-11-30
Enrollment: 119
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Parkinson's disease is a common neurodegenerative disorder in which patients experience progressive motor disability and many disabling non-motor symptoms. Recent studies have consistently found that people who do not use caffeine are at higher risk of developing Parkinson's disease. This suggests that caffeine may have potential as a treatment for PD.

In a pilot study of caffeine for daytime sleepiness in PD, there was evident benefit on the motor manifestations of disease. There have been other lines of evidence that have suggested caffeine could be useful in PD. This study is to evaluate the efficacy of caffeine 200 mg BID vs matching placebo for motor and non-motor aspects of disease. This will be in three stages. In the first six-month stage, medications will be held constant, to see whether caffeine does have motor benefits. Then we will perform a four-year extension stage to define if the effects of caffeine persist (or even magnify), and to see if caffeine helps reduce dose of other PD meds and/or prevents their side effects. Finally, we will finish with a six-month stage in which we will place all patients on caffeine - this will allow us to assess caffeine's use in later disease, but more importantly, will assess whether early use of caffeine produces long term changes beyond its immediate effects.


Eligibility criteria: Inclusion Criteria:

All patients must have idiopathic PD diagnosed as parkinsonism according to the UK brain bank criteria, and PD considered the likeliest underlying cause according to the treating physician. Other inclusion criteria include:

1. PD diagnosis: between 6 months and 8 years
2. Hoehn and Yahr stage I-III
3. Age at least 45 and less than 75 (to optimize survival over the 5-year trial).
4. Receiving symptomatic therapy for PD for at least 6 months. Dose must have been stable over the previous 3 months.

Exclusion Criteria:

1. Caffeine intake \>150 mg per day (i.e. more than one cup of filtered coffee per day) or prescribed adenosine antagonists - caffeine intake will be measured by a standardized intake questionnaire. Intake will be converted into estimated caffeine mg dose by standard caffeine-content charts.
2. Active peptic ulcer disease, or symptomatic gastroesophageal reflux disease.
3. Supraventricular cardiac arrhythmia (such as atrial fibrillation or atrial flutter) - Electrocardiogram will be measured at baseline to rule out supraventricular tachycardia.
4. Uncontrolled hypertension - systolic bp \>170 or diastolic bp \>110 on two readings.
5. Pre-menopausal women who are not using effective methods of birth control
6. Cognitive impairment, defined as MoCA \<23/30.
7. Moderate-Severe Depression, as defined by a Beck Depression Inventory score of \>19.
8. Changes to antiparkinsonian medication in the last 3 months, or changes to antiparkinsonian medication are anticipated during the next six months.
9. Current use of lithium or clozapine (pharmacokinetic interactions).

Primary outcomes:
measure: Motor manifestations associated with Parkinson's disease
timeFrame: every 6 months
Secondary outcomes:
measure: MDS-UPDRS components and subscales - each individual component will be assessed, including:
timeFrame: every 6 months
measure: Cognition
timeFrame: every 6 months
measure: Sleep
timeFrame: every 6 motnhs
measure: Quality of life
timeFrame: every 6 months
measure: Medication utilization
timeFrame: evry 6 months
measure: Tolerability and side effects of caffeine
timeFrame: every 6 motnhs
Other outcomes:
Locations:
city: Curitiba
country: Brazil
facility: Parana Parkinson Association - Pontifical Catholic University of Parana
state: PR
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic - University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: UBC Hospital - Pacific Parkinson's Research Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: Movement Disorder Clinic - Deer Lodge Centre
state: Manitoba
city: St-John's
country: Canada
facility: Memorial University of Newfoundland
state: Newfoundland and Labrador
city: Ottawa
country: Canada
facility: The Ottawa Hospital - Civic Campus
state: Ontario
city: Toronto
country: Canada
facility: Toronto western Hospital - Movement Disorders Research Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
Study officials:
affiliation: Research Insitute of the MUHC
name: Ronald B Postuma, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Postuma RB, Anang J, Pelletier A, Joseph L, Moscovich M, Grimes D, Furtado S, Munhoz RP, Appel-Cresswell S, Moro A, Borys A, Hobson D, Lang AE. Caffeine as symptomatic treatment for Parkinson disease (Cafe-PD): A randomized trial. Neurology. 2017 Oct 24;89(17):1795-1803. doi: 10.1212/WNL.0000000000004568. Epub 2017 Sep 27.