Parkinson's DiseasePhase 2NCT01190735
Caffeine for Motor Manifestations of Parkinson's Disease
A Phase 2 study testing Caffeine alkaloid in people with Parkinson's Disease, run by Ron Postuma at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Caffeine alkaloid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2010to Feb 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Subject has been diagnosed with idiopathic Parkinson's disease (stage I - IV Hoehn and Yahr)
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Caffeine for Motor Manifestations of Parkinson's Disease: An Open-Label Dose-Response Study.
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.
Read the 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.
- Conditions
- Parkinson's Disease
- Being tested
- Caffeine alkaloid
- 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
- Medical subject headings
- Parkinson Disease, Parkinsonian Disorders, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Neurodegenerative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caffeine alkaloidDrug
Also called Wake-Ups, 100mg tabs, NPN 00533629, serial no 5503701103, 200mg tabs, NPN, 80003474, serial no 5503701105
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Caffeine alkaloid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks
Secondary outcomes (10)
Epworth Sleepiness Scale (ESS)
Will systematically track changes in ESS.
Measured: 6 weeks
Unified Parkinson Disease Rating Scale(UPDRS): Part II
Systematically performing part II of the UPDRS, motor examination.
Measured: 6 weeks
Timed Up and Go (TUG)
This is a measure of gait and transfer speed.
Measured: 6 weeks
Clinical Global Impression of Change
Measured: 6 weeks
Pittsburgh Sleep Quality Index
Measured: 6 weeks
Fatigue Severity Scale
Measured: 6 weeks
The Parkinson's Disease Questionnaire - PDQ-39
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.
Measured: 6 weeks
Beck Depression Inventory
Self-administered questionnaire.
Measured: 6 weeks
Beck Anxiety Inventory
Self-administered questionnaire.
Measured: 6 weeks
UPDRS: Part I,II,IV
Systematically querying I (non-motor aspects of activities of daily living), II (motor aspects of activities of daily living) and IV (motor complications)
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2010 (estimated)
- Study startAug 2010
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ron Postuma
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor-investigator, Ron Postuma, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Ron Postuma, MD, Msc, Study director, McGill University Health Centre/Research Institute of the McGill University Health CentreRobert Altman, MD, Principal investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01190735
- Sponsor's protocol ID
- CIHR-219243
- Status last verified
- Apr 2015
- First submitted
- 26 Aug 2010
- Last updated
- 16 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Caffeine for Motor Manifestations of Parkinson's Disease: An Open-Label Dose-Response Study.
- ClinicalTrials.gov ID
- NCT01190735
- Acronym / sponsor ID
- CIHR-219243
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Ron PostumaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Aug 2010
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 30 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Caffeine | Experimental | Drug: Caffeine alkaloidEach 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 1. Subject has been diagnosed with idiopathic Parkinson's disease (stage I - IV Hoehn and Yahr)
Key exclusion criteria (11 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caffeine alkaloidAlso: Wake-Ups, 100mg tabs, NPN 00533629, serial no 5503701103, 200mg tabs, NPN, 80003474, serial no 5503701105The 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. | Drug | Caffeine |
Primary outcome
Tolerability
Time frame: 6 weeks
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.
10 secondary outcomes
Epworth Sleepiness Scale (ESS)
Time frame: 6 weeks
Unified Parkinson Disease Rating Scale(UPDRS): Part II
Time frame: 6 weeks
Timed Up and Go (TUG)
Time frame: 6 weeks
Clinical Global Impression of Change
Time frame: 6 weeks
Pittsburgh Sleep Quality Index
Time frame: 6 weeks
Fatigue Severity Scale
Time frame: 6 weeks
The Parkinson's Disease Questionnaire - PDQ-39
Time frame: 6 weeks
Beck Depression Inventory
Time frame: 6 weeks
Beck Anxiety Inventory
Time frame: 6 weeks
UPDRS: Part I,II,IV
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2015.
- Ongoing study investigating caffeine for excessive daytime somnolence in Parkinson's DiseaseLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ron Postuma, MD, Msc study director
McGill University Health Centre/Research Institute of the McGill University Health Centre
Robert Altman, MD principal investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Caffeine alkaloid in people with Parkinson's Disease, run by Ron Postuma at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerability (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2015.