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

Parkinson's Disease Clinical Trial

— DALI  

Official title:

Effects of a Dopamine Agonist on Pharmacodynamics of Levodopa in Parkinson's Disease: a Double-Blind Placebo Controlled Crossover Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00666653
• Other study ID #: 697
• Status: Completed
• Phase: Phase 1
• First received: April 23, 2008
• Last updated: April 24, 2008
• Start date: July 2003
• Est. completion date: May 2007

Study information

• Verified date: April 2008
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: May 2007
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• pramipexole

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Oregon Health and Science University	Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve of motor function based on finger tapping scores		2 months	No
Secondary	Dyskinesia rating score		2 months	No
Secondary	Gait performance		2 months	No