Caffeine as a Therapy for Parkinson's Disease

NCT01738178 | Completed Phase 3 DMC

• 1 other identifier: 2778
• Study Type: interventional
• Target: 119
• Locations: 2 countries
• Sites: 8

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.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• 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).

  every 6 months

Secondary Outcomes (6)

• MDS-UPDRS components and subscales - each individual component will be assessed, including:

  every 6 months

• Cognition

  every 6 months

• Sleep

  every 6 motnhs

• Quality of life

  every 6 months

• Medication utilization

  evry 6 months

Study Arms (2)

Control - Placebo

PLACEBO COMPARATOR

These participants will receive placebo tablets during the first 5 years

Drug: Placebo

Caffeine group

ACTIVE COMPARATOR

This group of participants will receive caffeine tablets.

Drug: Caffeine

Interventions

Caffeine DRUG

Caffeine group

Placebo DRUG

Control - Placebo

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Pontifícia Universidade Católica do Paraná: collaborator
• University of Calgary: collaborator
• University of Newfoundland and Eastern Health: collaborator
• University Health Network, Toronto: collaborator
• UBC Hospital: collaborator
• Movement Disorder Clinic - Deer Lodge Centre: collaborator
• The Ottawa Hospital: collaborator

Study Sites (8)

Parana Parkinson Association - Pontifical Catholic University of Parana

Curitiba, Paraná, 80240-021, Brazil

Location

Heritage Medical Research Clinic - University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

UBC Hospital - Pacific Parkinson's Research Centre

Vancouver, British Columbia, V6T 2B5, Canada

Location

Movement Disorder Clinic - Deer Lodge Centre

Winnipeg, Manitoba, R3J 2H7, Canada

Location

Memorial University of Newfoundland

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

The Ottawa Hospital - Civic Campus

Ottawa, Ontario, K1Y 4E9, Canada

Location

Toronto western Hospital - Movement Disorders Research Centre

Toronto, Ontario, M5T 2S8, Canada

Location

McGill University Health Center

Montreal, Quebec, H3G 1A4, Canada

Location

Related Publications (1)

• 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.

  PMID: 28954882 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Caffeine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ronald B Postuma, MD, MSc

  Research Insitute of the MUHC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: November 30, 2012
• Study Start: April 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 22, 2017

Record last verified: 2017-03

Locations

BR (1); CA (7)