Back to resultsCaffeine as a Therapy for Parkinson's Disease
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Caffeine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease
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:
- PD diagnosis: between 6 months and 8 years
- Hoehn and Yahr stage I-III
- Age at least 45 and less than 75 (to optimize survival over the 5-year trial).
- Receiving symptomatic therapy for PD for at least 6 months. Dose must have been stable over the previous 3 months.
Exclusion Criteria:
- 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.
- Active peptic ulcer disease, or symptomatic gastroesophageal reflux disease.
- Supraventricular cardiac arrhythmia (such as atrial fibrillation or atrial flutter) - Electrocardiogram will be measured at baseline to rule out supraventricular tachycardia.
- Uncontrolled hypertension - systolic bp >170 or diastolic bp >110 on two readings.
- Pre-menopausal women who are not using effective methods of birth control
- Cognitive impairment, defined as MoCA <23/30.
- Moderate-Severe Depression, as defined by a Beck Depression Inventory score of >19.
- Changes to antiparkinsonian medication in the last 3 months, or changes to antiparkinsonian medication are anticipated during the next six months.
- Current use of lithium or clozapine (pharmacokinetic interactions).
Sites / Locations
- Parana Parkinson Association - Pontifical Catholic University of Parana
- Heritage Medical Research Clinic - University of Calgary
- UBC Hospital - Pacific Parkinson's Research Centre
- Movement Disorder Clinic - Deer Lodge Centre
- Memorial University of Newfoundland
- The Ottawa Hospital - Civic Campus
- Toronto western Hospital - Movement Disorders Research Centre
- McGill University Health Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Control - Placebo
Caffeine group
Arm Description
These participants will receive placebo tablets during the first 5 years
This group of participants will receive caffeine tablets.
Outcomes
Primary Outcome Measures
Motor manifestations associated with Parkinson's disease
For each stage of the study, the MDS-Unified Parkinson Disease Rating Scale (MDS-UPDRS)will be used as the primary outcome. The MDS-UPDRS is the standard scale used for grading severity of PD - its revised 2008 version has more standardized motor assessment, better sensitivity to change in early-mid stages, and a broader assessment of non-motor PD. It starts with a patient self-administered questionnaire covering activities of daily living, motor symptoms, and non-motor domains. There is then a scored clinical interview assessing cognitive and psychiatric symptoms and motor complications. The Hoehn and Yahr scale (5-point overall disease severity index) is included3. Finally, there is a formal examination component (Part III) (performed in the medication 'on' state for this study).
Secondary Outcome Measures
MDS-UPDRS components and subscales - each individual component will be assessed, including:
motor symptoms, according to each subscale question. These include speech deficits, swallowing dysfunction, motor activities of daily living (dressing, feeding, turns in bed, etc), tremor, gait slowing, freezing, and falls
non-motor symptoms, according to each subscale question. These include constipation, urinary dysfunction, sexual dysfunction, orthostatic symptoms, depression, anxiety, cognitive symptoms, apathy, somnolence, insomnia, pain, and fatigue.
motor complications - motor fluctuations and dyskinesia
Hoehn and Yahr staging (a five-point global staging system for PD).
Cognition
Although cognitive symptoms are addressed with the UPRDS, we will include two objective measures, the Montreal Cognitive Assessment (MoCA), and Mini-mental State Examination. The MoCA is a brief cognitive test, which is used extensively in PD. The MMSE will be used in diagnosis of dementia. Dementia will be assessed according to Level I MDS criteria. ADL impairment due to cognitive loss will be documented according to MDS criteria.
Sleep
Because caffeine may have special effectiveness for sleep disorders, we will include additional sleep questionnaires, including
the SCOPA-sleep8 nighttime scale.
the SCOPA-sleep8 daytime scale
the REM sleep behavior disorder single-question screen (RBD1Q)
Quality of life
The Parkinson's Disease Questionnaire-8 is a quality of life index for PD with 8 self-administered items assessing motor function, gait, mood, cognition, etc.
Medication utilization
To assess caffeine's potential medication-sparing benefit, we will quantify all medications at each visit. Levodopa-dose equivalents will be calculated with standard criteria. Total medication cost will be calculated using current Canadian pharmacy pricing.
Tolerability and side effects of caffeine
A structured questionnaire will screen for irritability, symptoms of gastrointestinal reflux, diarrhea, sleepiness, palpitations, sweating, and tremulousness. In addition, open-ended questions will allow reporting of other side effects. Blood pressure will be measured at each visit to exclude new-onset hypertension, and orthostatic hypotension will be objective assessed with blood pressure measurements lying and standing (1 minute).
Full Information
NCT ID
NCT01738178
First Posted
November 28, 2012
Last Updated
March 21, 2017
Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators
Pontifícia Universidade Católica do Paraná, University of Calgary, University of Newfoundland and Eastern Health, University Health Network, Toronto, UBC Hospital, Movement Disorder Clinic - Deer Lodge Centre, The Ottawa Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01738178
Brief Title
Caffeine as a Therapy for Parkinson's Disease
Official Title
Caffeine as a Therapeutic Agent in Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
May 1, 2016 (Actual)
Study Completion Date
December 1, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators
Pontifícia Universidade Católica do Paraná, University of Calgary, University of Newfoundland and Eastern Health, University Health Network, Toronto, UBC Hospital, Movement Disorder Clinic - Deer Lodge Centre, The Ottawa Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
119 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control - Placebo
Arm Type
Placebo Comparator
Arm Description
These participants will receive placebo tablets during the first 5 years
Arm Title
Caffeine group
Arm Type
Active Comparator
Arm Description
This group of participants will receive caffeine tablets.
Intervention Type
Drug
Intervention Name(s)
Caffeine
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Motor manifestations associated with Parkinson's disease
Description
For each stage of the study, the MDS-Unified Parkinson Disease Rating Scale (MDS-UPDRS)will be used as the primary outcome. The MDS-UPDRS is the standard scale used for grading severity of PD - its revised 2008 version has more standardized motor assessment, better sensitivity to change in early-mid stages, and a broader assessment of non-motor PD. It starts with a patient self-administered questionnaire covering activities of daily living, motor symptoms, and non-motor domains. There is then a scored clinical interview assessing cognitive and psychiatric symptoms and motor complications. The Hoehn and Yahr scale (5-point overall disease severity index) is included3. Finally, there is a formal examination component (Part III) (performed in the medication 'on' state for this study).
Time Frame
every 6 months
Secondary Outcome Measure Information:
Title
MDS-UPDRS components and subscales - each individual component will be assessed, including:
Description
motor symptoms, according to each subscale question. These include speech deficits, swallowing dysfunction, motor activities of daily living (dressing, feeding, turns in bed, etc), tremor, gait slowing, freezing, and falls
non-motor symptoms, according to each subscale question. These include constipation, urinary dysfunction, sexual dysfunction, orthostatic symptoms, depression, anxiety, cognitive symptoms, apathy, somnolence, insomnia, pain, and fatigue.
motor complications - motor fluctuations and dyskinesia
Hoehn and Yahr staging (a five-point global staging system for PD).
Time Frame
every 6 months
Title
Cognition
Description
Although cognitive symptoms are addressed with the UPRDS, we will include two objective measures, the Montreal Cognitive Assessment (MoCA), and Mini-mental State Examination. The MoCA is a brief cognitive test, which is used extensively in PD. The MMSE will be used in diagnosis of dementia. Dementia will be assessed according to Level I MDS criteria. ADL impairment due to cognitive loss will be documented according to MDS criteria.
Time Frame
every 6 months
Title
Sleep
Description
Because caffeine may have special effectiveness for sleep disorders, we will include additional sleep questionnaires, including
the SCOPA-sleep8 nighttime scale.
the SCOPA-sleep8 daytime scale
the REM sleep behavior disorder single-question screen (RBD1Q)
Time Frame
every 6 motnhs
Title
Quality of life
Description
The Parkinson's Disease Questionnaire-8 is a quality of life index for PD with 8 self-administered items assessing motor function, gait, mood, cognition, etc.
Time Frame
every 6 months
Title
Medication utilization
Description
To assess caffeine's potential medication-sparing benefit, we will quantify all medications at each visit. Levodopa-dose equivalents will be calculated with standard criteria. Total medication cost will be calculated using current Canadian pharmacy pricing.
Time Frame
evry 6 months
Title
Tolerability and side effects of caffeine
Description
A structured questionnaire will screen for irritability, symptoms of gastrointestinal reflux, diarrhea, sleepiness, palpitations, sweating, and tremulousness. In addition, open-ended questions will allow reporting of other side effects. Blood pressure will be measured at each visit to exclude new-onset hypertension, and orthostatic hypotension will be objective assessed with blood pressure measurements lying and standing (1 minute).
Time Frame
every 6 motnhs
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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:
PD diagnosis: between 6 months and 8 years
Hoehn and Yahr stage I-III
Age at least 45 and less than 75 (to optimize survival over the 5-year trial).
Receiving symptomatic therapy for PD for at least 6 months. Dose must have been stable over the previous 3 months.
Exclusion Criteria:
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.
Active peptic ulcer disease, or symptomatic gastroesophageal reflux disease.
Supraventricular cardiac arrhythmia (such as atrial fibrillation or atrial flutter) - Electrocardiogram will be measured at baseline to rule out supraventricular tachycardia.
Uncontrolled hypertension - systolic bp >170 or diastolic bp >110 on two readings.
Pre-menopausal women who are not using effective methods of birth control
Cognitive impairment, defined as MoCA <23/30.
Moderate-Severe Depression, as defined by a Beck Depression Inventory score of >19.
Changes to antiparkinsonian medication in the last 3 months, or changes to antiparkinsonian medication are anticipated during the next six months.
Current use of lithium or clozapine (pharmacokinetic interactions).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald B Postuma, MD, MSc
Organizational Affiliation
Research Insitute of the MUHC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Parana Parkinson Association - Pontifical Catholic University of Parana
City
Curitiba
State/Province
PR
ZIP/Postal Code
80240-021
Country
Brazil
Facility Name
Heritage Medical Research Clinic - University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
UBC Hospital - Pacific Parkinson's Research Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2B5
Country
Canada
Facility Name
Movement Disorder Clinic - Deer Lodge Centre
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3J 2H7
Country
Canada
Facility Name
Memorial University of Newfoundland
City
St-John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
The Ottawa Hospital - Civic Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
Toronto western Hospital - Movement Disorders Research Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Facility Name
McGill University Health Center
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1A4
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
28954882
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.
Results Reference
derived
Learn more about this trial
Caffeine as a Therapy for Parkinson's Disease
We'll reach out to this number within 24 hrs