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Parkinson's Disease Isradipine Safety Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00753636
Recruitment Status : Completed
First Posted : September 16, 2008
Results First Posted : July 1, 2011
Last Update Posted : October 5, 2020
Sponsor:
Collaborator:
Northwestern Memorial Hospital
Information provided by (Responsible Party):
Tanya Simuni, Northwestern University

Tracking Information
First Submitted Date  ICMJE September 13, 2008
First Posted Date  ICMJE September 16, 2008
Results First Submitted Date  ICMJE January 13, 2011
Results First Posted Date  ICMJE July 1, 2011
Last Update Posted Date October 5, 2020
Study Start Date  ICMJE April 2008
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 8, 2011)
Tolerability of Isradipine Based on the Number of Participants That Complete the Study [ Time Frame: 1 year ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 15, 2008)
Primary outcome measure is tolerability of isradipine based on the proportion of patients that complete the study. [ Time Frame: 1 year ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2011)
  • 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 ]
  • Number of Participants That Tolerated Each Dose of Isradipine [ Time Frame: 1 year ]
    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 [ Time Frame: 1 year ]
    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 [ Time Frame: 1 year ]
  • Change in Motor UPDRS Scores: Baseline vs. Final Visit [ Time Frame: 12 weeks ]
    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 [ Time Frame: 1 year ]
    Mean Plasma Concentration (+/- SD ng/mL)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2008)
  • Safety of the standard titration schedule in PD population as measured by the proportion of patients that are able to increase the dose to 20 mg daily. [ Time Frame: 1 year ]
  • Comparison of tolerability of isradipine across the titration dose range between PD patients treated with dopaminergic therapy and not treated with dopaminergic therapy. [ Time Frame: 1 year ]
  • Comparison of tolerability of isradipine across the titration dose range between PD patients treated with antihypertensive agent and not on antihypertensive agent. [ Time Frame: 1 year ]
  • Analysis of the dose best tolerated in PD population- the median number of patients that were treated with each dose of isradipine. [ Time Frame: 1 year ]
  • Impact of isradipine on PD motor disability as measured by UPDRS scale [ Time Frame: 1 year ]
  • Pharmacokinetic data - correlation of the serum concentration and dosage exposure across the dose range of isradipine. [ Time Frame: 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Parkinson's Disease Isradipine Safety Study
Official Title  ICMJE Phase II Safety and Tolerability of Isradipine (A Potential Neuroprotective Agent) in Patients With Parkinson's Disease- Stage II
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Parkinson's Disease
Intervention  ICMJE Drug: 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.
Other Name: Isradipine
Study Arms  ICMJE Experimental: Dynacirc CR (Isradipine)
Dynacirc CR (Isradipine) will start at 5mg dose and increased in increments of 5mg every 2 weeks
Intervention: Drug: Dynacirc CR (Isradipine)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 8, 2011)
31
Original Estimated Enrollment  ICMJE
 (submitted: September 15, 2008)
20
Actual Study Completion Date  ICMJE February 2010
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00753636
Other Study ID Numbers  ICMJE Isradipine II
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tanya Simuni, Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE Northwestern Memorial Hospital
Investigators  ICMJE
Principal Investigator: Tanya Simuni, M.D. Northwestern University
PRS Account Northwestern University
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP