Parkinson's Disease Isradipine Safety Study

NCT ID: NCT00753636

Last Updated: 2021-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2010-02-28

Brief 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.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Isradipine; Neuroprotection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dynacirc CR (Isradipine)

Dynacirc CR (Isradipine) will start at 5mg dose and increased in increments of 5mg every 2 weeks

Group Type: EXPERIMENTAL

Dynacirc CR (Isradipine)

Intervention Type: DRUG

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.

Interventions

Dynacirc CR (Isradipine)

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.

Intervention Type: DRUG

Other Intervention Names

Isradipine

Eligibility Criteria

Inclusion Criteria

1. Patients with idiopathic Parkinson's disease age 30-75

2. Hoehn and Yahr stage <2.5

3. PD duration less than 5 years

4. For the subjects treated with PD medications, the regimen has to be stable for >1 month prior to enrollment

Exclusion Criteria

1. Atypical Parkinsonian syndrome

2. 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

3. 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.

4. Presence of other medical conditions that in the opinion of the investigator will preclude safe use of the drug.

5. Presence of cognitive dysfunction as determined by MMSE score <24

6. Failure to sign the informed consent

7. Inability to cooperate with the study procedures

8. Presence of motor fluctuations

9. History of bradycardia defined as heart rate < 55

10. 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

11. Participation in other investigational drug trials within 30 days prior to screening

12. History of brain surgery for Parkinson's Disease.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwestern Memorial Hospital

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Tanya Simuni

Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tanya Simuni, M.D.

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

710 N. Lake Shore Dr.

Chicago, Illinois, United States

Countries

United States

Other Identifiers

Isradipine II

Identifier Type: -

Identifier Source: org_study_id