Effects of a Dopamine Agonist on Pharmacodynamics of Levodopa in Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 1

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.
    

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.
    

Intervention name(s): pramipexole
Intervention type(s): Drug
Intervention MeSH terms: Pramipexole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Parkinson's disease; Dopamine Agonist; Levodopa; Pharmacokinetics; Dyskinesia