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

Oregon Health & Science University (OHSU)

Status and phase

Completed

Phase 1

Conditions

Parkinson's Disease

Treatments

Drug: pramipexole

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00666653

697

Details and patient eligibility

About

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.

Full 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.

Enrollment

13 patients

Sex

All

Ages

30 to 80 years old

Volunteers

No Healthy Volunteers

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