Parkinson's Disease Isradipine Safety Study

This study has been completed.
Sponsor:
Collaborator:
Northwestern Memorial Hospital
Information provided by (Responsible Party):
Tanya Simuni, Northwestern University
ClinicalTrials.gov Identifier:
NCT00753636
First received: September 13, 2008
Last updated: April 29, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
Drug: Dynacirc CR (Isradipine)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Safety and Tolerability of Isradipine (A Potential Neuroprotective Agent) in Patients With Parkinson's Disease- Stage II

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Tolerability of Isradipine Based on the Number of Participants That Complete the Study [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Number of Participants That Tolerated Each Dose of Isradipine [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
  • Change in Motor UPDRS Scores: Baseline vs. Final Visit [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    Mean Plasma Concentration (+/- SD ng/mL)


Enrollment: 31
Study Start Date: April 2008
Study Completion Date: February 2010
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Isradipine 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

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00753636

Locations
United States, Illinois
710 N. Lake Shore Dr.
Chicago, Illinois, United States, 60610
Sponsors and Collaborators
Northwestern University
Northwestern Memorial Hospital
Investigators
Principal Investigator: Tanya Simuni, M.D. Northwestern University
  More Information

Additional Information:
No publications provided

Responsible Party: Tanya Simuni, Professor of Neurology, Northwestern University
ClinicalTrials.gov Identifier: NCT00753636     History of Changes
Other Study ID Numbers: Isradipine II
Study First Received: September 13, 2008
Results First Received: January 13, 2011
Last Updated: April 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
Parkinson's disease
Isradipine
Neuroprotection

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Isradipine
Neuroprotective Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Antihypertensive Agents
Protective Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 23, 2014