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Parkinson's Disease Isradipine Safety Study

Primary Purpose

Parkinson's Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Dynacirc CR (Isradipine)

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's disease, Isradipine, Neuroprotection

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

710 N. Lake Shore Dr.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dynacirc CR (Isradipine)

Arm Description

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

Outcomes

Primary Outcome Measures

Tolerability of Isradipine Based on the Number of Participants That Complete the Study

Secondary Outcome Measures

Safety of the Standard Titration Schedule in PD Population as Measured by the Number of Patients That Are Able to Increase the Dose to 20 mg Daily

Number of Participants That Tolerated Each Dose of Isradipine

Tolerability= maximum tolerated dose

Number of Participants That Tolerated Each Dose Level of Isradipine Between PD Patients Treated With Antihypertensive Agent and Not on Antihypertensive Agent

At the time of enrollment, some patients were currently being treated with antihypertensive agents including Propanolol, Toprol, Lisinopril, Diovan, Norvasc. HTN+: Participants on an antihypertensive agent HTN-: Participants not on an antihypertensive agent

Number of Participants That Completed the Study at Each Dose Level of Isradipine

Change in Motor UPDRS Scores: Baseline vs. Final Visit

Baseline visit = Week 0 Final visit = Week 12 Unified Parkinson's Disease Rating Scale (UPDRS)is made up of the following sections: Part I: evaluation of Mentation, behavior, and mood Part II: self evaluation of the activities of daily life Part III: clinician-scored motor evaluation Part IV: Hoehn and Yahr stating of severity of Parkinson disease. Part V: Schwab and England ADL scale Only part three was used for this assessment. The higher the UPDRS score, the greater the disability from PD. The range for scores for Section III is 0 to 108.

Pharmacokinetic Data - Mean Serum Concentration and Dosage Exposure Across the Dose Range of Isradipine

Mean Plasma Concentration (+/- SD ng/mL)

Full Information

NCT ID

NCT00753636

First Posted

September 13, 2008

Last Updated

November 11, 2021

Sponsor

Northwestern University

Collaborators

Northwestern Memorial Hospital

1. Study Identification

Unique Protocol Identification Number

NCT00753636

Brief Title

Parkinson's Disease Isradipine Safety Study

Official Title

Phase II Safety and Tolerability of Isradipine (A Potential Neuroprotective Agent) in Patients With Parkinson's Disease- Stage II

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Completed

Study Start Date

April 2008 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

Collaborators

Northwestern Memorial Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson's Disease

Keywords

Parkinson's disease, Isradipine, Neuroprotection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

31 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dynacirc CR (Isradipine)

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Dynacirc CR (Isradipine)

Other Intervention Name(s)

Isradipine

Intervention Description

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.

Primary Outcome Measure Information:

Title

Tolerability of Isradipine Based on the Number of Participants That Complete the Study

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Safety of the Standard Titration Schedule in PD Population as Measured by the Number of Patients That Are Able to Increase the Dose to 20 mg Daily

Time Frame

1 year

Title

Number of Participants That Tolerated Each Dose of Isradipine

Description

Tolerability= maximum tolerated dose

Time Frame

1 year

Title

Number of Participants That Tolerated Each Dose Level of Isradipine Between PD Patients Treated With Antihypertensive Agent and Not on Antihypertensive Agent

Description

Time Frame

1 year

Title

Number of Participants That Completed the Study at Each Dose Level of Isradipine

Time Frame

1 year

Title

Change in Motor UPDRS Scores: Baseline vs. Final Visit

Description

Time Frame

12 weeks

Title

Pharmacokinetic Data - Mean Serum Concentration and Dosage Exposure Across the Dose Range of Isradipine

Description

Mean Plasma Concentration (+/- SD ng/mL)

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tanya Simuni, M.D.

Organizational Affiliation

Northwestern University

Official's Role

Principal Investigator

Facility Information:

Facility Name

710 N. Lake Shore Dr.

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60610

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Parkinson's Disease Isradipine Safety Study

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