Effects of a Dopamine Agonist on Pharmacodynamics of Levodopa in Parkinson's Disease (DALI)

This study has been completed.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by:
Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT00666653
First received: April 23, 2008
Last updated: April 24, 2008
Last verified: April 2008
  Purpose

The purpose of this study is to determine whether there is a benefit to giving a dopamine agonist to a patient with Parkinson's disease who is already being treated with levodopa.


Condition Intervention Phase
Parkinson's Disease
Drug: pramipexole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of a Dopamine Agonist on Pharmacodynamics of Levodopa in Parkinson's Disease: a Double-Blind Placebo Controlled Crossover Study

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • Area Under the Curve of motor function based on finger tapping scores [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dyskinesia rating score [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Gait performance [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: July 2003
Study Completion Date: May 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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%)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00666653

Locations
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Boehringer Ingelheim
Investigators
Principal Investigator: Matthew A Brodsky, MD Oregon Health and Science University
  More Information

No publications provided by Oregon Health and Science University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Matthew Brodsky M.D., Oregon Health & Science University
ClinicalTrials.gov Identifier: NCT00666653     History of Changes
Other Study ID Numbers: 697
Study First Received: April 23, 2008
Last Updated: April 24, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:
Parkinson's disease
Dopamine Agonist
Levodopa
Pharmacokinetics
Dyskinesia

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dopamine
Dopamine Agents
Levodopa
Pramipexole
Dopamine Agonists
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Antioxidants

ClinicalTrials.gov processed this record on August 19, 2014