- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00666653
Effects of a Dopamine Agonist on Pharmacodynamics of Levodopa in Parkinson's Disease (DALI)
Effects of a Dopamine Agonist on Pharmacodynamics of Levodopa in Parkinson's Disease: a Double-Blind Placebo Controlled Crossover Study
Study Overview
Detailed Description
Patients with idiopathic PD based on London Brain Bank criteria as determined by an OHSU movement disorder specialist entered the study. They gave informed consent to a protocol approved by the Oregon Health and Science University Institutional Review Board and General Clinical Research Center (GCRC) Review Committee.
Patients were on long-term levodopa therapy, and had motor fluctuations and dyskinesia as determined during screening. Subjects were screened with finger tapping (FT) in the practically defined OFF motor state, having been off LD overnight, and in the practically defined ON motor state. To qualify, they had to have a minimum 10% improvement in the ON state.
The trial was a randomized, double-blind, placebo-controlled crossover study with subjects on pramipexole for 4 weeks and an identically appearing placebo for 4 weeks. The response to two-hour LD infusions at 0.5 (threshold) and 1.0 (suprathreshold) mg/kg/hr were examined at the end of each 4 week treatment period.
The primary outcome was finger-tapping speed, as a surrogate marker of bradykinesia, over a seven hour time period. The area under the curve (AUC) was calculated as finger taps x minutes (FTM). Secondary outcomes measured included peak motor response, as measured by FT, walking speed, dyskinesia, time-to-ON (defined as a 10% increase in finger tapping speed over the baseline), and effects of LD infusion on subjects' perceived mood, anxiety and fatigue.
Subjects were randomized to receive either pramipexole (PPX) or placebo for the initial 5 weeks of the study. The PPX and placebo was titrated up over 9 days to a target dose of 1.0mg TID. If they were already taking a DA, this was tapered and discontinued while the study medication was titrated upward. Their LD was continued according to the subjects normal schedule during this time period, as well as any other antiparkinsonian medications they were taking.
After a maintenance phase of 4 weeks on study medication (PPX 1.0mg TID or placebo TID) subjects were admitted in the evening to the inpatient GCRC at OHSU. Their last LD dose was given no later than 10 pm and all other PD medications were withheld after 10 pm. They practiced FT sessions on the night of admission. At 7 AM the next morning, a dose of the study drug was given and an IV line was placed. An IV levodopa infusion was administered starting at 9 am, continuously over 2 hours at a rate of either 0.5mg/kg/hr or 1.0 mg/kg/hr. The infusion rate was blinded and randomized. The infusion was stopped at 11 am. After 2:00 PM and when subjects were deemed "off", the usual antiparkinson medications were reinstituted.
FT, tremor, walking (timed and # of steps), dyskinesia, and a "global" PD scale were measured by research nurses, and subjects completed visual analogue scales (VASs) for anxiety, fatigue and mood every 30 minutes from 7:00 AM until 2:00 PM.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Oregon
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Portland, Oregon, United States, 97239
- Oregon Health & Science University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 30-80
- Idiopathic PD Hoehn & Yahr stage 2-4,
- diagnosed by 2 of the 3 cardinal motor features
- Fluctuation response to levodopa
- Dyskinesia
- No other historical, laboratory or physical signs to suggest an alternate diagnosis
- No significant dementia, MMSE>24
- On oral levodopa therapy
Exclusion Criteria:
- dementia
- psychosis
- severe anxiety
- unstable cardiovascular disease
- uncontrolled hypertension
- history of cardiac arrhythmias
- active peptic ulcer disease
- anemia (HCT<32%)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Area Under the Curve of motor function based on finger tapping scores
Time Frame: 2 months
|
2 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Dyskinesia rating score
Time Frame: 2 months
|
2 months
|
Gait performance
Time Frame: 2 months
|
2 months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Matthew A Brodsky, MD, Oregon Health and Science University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Parkinson Disease
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- Dopamine Agonists
- Dopamine Agents
- Antioxidants
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Pramipexole
Other Study ID Numbers
- 697 (Other Identifier: UNC)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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