This study will evaluate the effects of an experimental drug called JP-1730 on Parkinson's
disease symptoms and on dyskinesias (involuntary movements) that develop as a result of
long-term treatment with levodopa. JP-1730 affects chemical messengers believed to affect
Parkinson's disease symptoms.
Patients between 30 and 80 years of age with relatively advanced Parkinson's disease may be
eligible for this 3-phase study.
- Phase 1 - Baseline evaluation
Participants will be evaluated with a medical history, physical examination, detailed
neurologic evaluation, routine blood tests, urinalysis and an electrocardiogram. They will
also have a 24-hour holter monitor (heart monitoring) and cardiology consultation. A chest
X-ray and MRI or CT scan of the brain will be done if needed. Patients will, if possible,
stop taking all antiparkinsonian medications except levodopa (Sinemet) for one month before
the study begins and throughout its duration. (If necessary, patients may use short-acting
dopamine agonists, such as Mirapex and Requip.)
- Phase 2 - Dose Finding Phase
For 2 to 3 days, patients will be admitted to the NIH Clinical Center for a levodopa (a
dopamine agonist) dose-finding procedure. For this procedure, patients stop taking Sinemet
and instead have levodopa, and subsequently apomorphine, infused through a vein. During the
infusions, the drug dose is increased slowly until either 1) parkinsonian symptoms improve,
2) unacceptable side effects occur, or 3) the maximum study dose is reached. Symptoms are
monitored frequently to find the optimal dose. (Patients who have had dosing infusions in the
last 3 months will not have to undergo this phase of the study.)
- Phase 3 - Active Study Phase
Within 3 months of the dose-finding phase, treatment will begin. Patients will receive seven
doses of JD-1730 or placebo (an inactive substance) via puffs from an oral spray together
with levodopa infusions over a 3-week period. The doses are given on days 1, 2, and 3 of the
first week and then approximately twice a week for the next 2 weeks. For these doses,
patients are hospitalized 4 days the first week and 2 days each for the next 2 weeks. All
participants will receive placebo at some time during the study, and a few patients, selected
at random, will receive only placebo the entire 3 weeks. The procedure for the infusions is
the same as that for the dose-finding phase, with frequent evaluation of symptoms. Also,
small blood samples are drawn up to three times each study day. At the end of the third week,
patients will be discharged from the hospital. Their anti-parkinsonian medications may be
readjusted, as needed. Patients will be contacted 2 weeks after the end of the study for a
check on side effects and, if necessary, will be scheduled for a follow-up evaluation at the
clinic.
In addition to the above procedures, patients will be asked to have an optional lumbar a
puncture (spinal tap) on the first and last days of the study to measure various brain
chemicals and drug levels that cannot be measured in blood and urine. For this procedure, a
local anesthetic is given and a needle is inserted in the space between the bones (vertebrae)
in the lower back. About 2 tablespoons of fluid is collected through the needle.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)