Parkinson's Disease Isradipine Safety Study
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      The objective of this study is to establish the safety and tolerability of isradipine,
      sustained release preparation in patients with PD. This study is a logical continuation of
      the project that is being completed now and is conducted in preparation to NIH submission of
      the pivotal study on the efficacy of this agent for neuroprotection in PD. This study is
      conducted in parallel with Dr. Surmeier's work on further development of the preclinical
      data. The focus of his work now is to establishing the correlation between the dose that
      demonstrated neuroprotective effect in animal model and the dose used for clinical practice.

      Hypothesis 1: Patients with PD will be able to tolerate isradipine across the FDA recommended
      dose range. We expect 10% attrition due to hypotensive effect of the agent.

      Hypothesis 2: Patients with PD and concomitant stable hypertension will be able to tolerate
      isradipine provided that the dose of the concomitant antihypertensive agent is adjusted based
      on the blood pressure reading.
    

Detailed description: 
      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.
    

Intervention name(s): Dynacirc CR (Isradipine)
Intervention type(s): Drug
Intervention description(s): Dynacirc CR is given by the recommended schedule for titration. Subjects start on a 5mg dose and are increased in increments of 5mg every 2 weeks provided that the subjects do not have significant adverse events or symptomatic orthostatic hypotension.
Other intervention name(s): Isradipine
Intervention MeSH terms: Isradipine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Parkinson's disease; Isradipine; Neuroprotection