Parkinson's Disease Isradipine Safety Study

Isradipine safety profile Isradipine, FDA approved for treatment of hypertension since 1990, has a well established data on its efficacy and safety in the hypertensive population (see package insert, Appendix 3). The side effect profile of isradipine is related to the primary mechanism of action of the agent as a vasodilator of the vascular smooth muscles and myocardium, and includes hypotension, bradycardia, weakness, and syncope. As per package insert, the most common adverse effects are headache (13.7% with active treatment versus 14% placebo), dizziness (7.3 vs 4.4) and peripheral edema as reflection of the vasodilatory effect which is dose dependent with incidence of about 3.5% at 5 mg, 8.7% at 10 mg and 8.5% at 20 mg. Of note the incidence of edema is substantially lower compared to CR preparation (9:13:36% for the respective doses). The other side effects include angina, asthenia, flushing, heart failure, and palpitations. According to the package insert, the adverse effects are usually not serious, dose dependent, and respond well to dose reduction or discontinuation of therapy. Isradipine has no effect on atrioventricular or sinoatrial conduction. The only absolute contraindications for isradipine are hypersensitivity to DHP compounds and hypotension defined as systolic blood pressure below 90 mm Hg. Until our studies, isradipine has not been tested in the PD population.

Inclusion criteria

• Patients with idiopathic Parkinson's disease age 30-75
• Hoehn and Yahr stage <2.5
• PD duration less than 5 years
• For the subjects treated with PD medications, the regimen has to be stable for >1 month prior to enrollment

Exclusion criteria

• Atypical Parkinsonian syndrome
• Patients with history of stable hypertension treated with other antihypertensive agents will be allowed provided that the doses of concomitant anti HTN therapy can be reduced/adjusted during the study based on the BP readings. The number of concomitant antihypertensive agents should not exceed two. The dose of concomitant antihypertensive agents has to be stable for > 1 month
• Presence of orthostatic hypotension at the screening visit defined as > 20 mmHg change in systolic BP and 10mm change in diastolic BP after 2 min of standing, or baseline BP <90/60.
• Presence of other medical conditions that in the opinion of the investigator will preclude safe use of the drug.
• Presence of cognitive dysfunction as determined by MMSE score <24
• Failure to sign the informed consent
• Inability to cooperate with the study procedures
• Presence of motor fluctuations
• History of bradycardia defined as heart rate < 55
• Women of childbearing potential who are not surgically sterilized have to use a reliable measure of contraception and have a negative urine pregnancy test at screening
• Participation in other investigational drug trials within 30 days prior to screening
• History of brain surgery for Parkinson's Disease.