Efficacy of Isradipine in Early Parkinson Disease
- Conditions
- Parkinson Disease
- Interventions
- Drug: Placebo (for Isradipine)
- Registration Number
- NCT02168842
- Lead Sponsor
- University of Rochester
- Brief Summary
The purpose of the study is to determine whether treatment with isradipine is effective in slowing the progression of Parkinson disease disability.
- Detailed Description
The study will enroll 336 participants in this multi-center study at approximately 56 sites across the US and Canada. In this study, we are comparing 10 mg of Isradipine to Placebo for treatment of newly diagnosed PD patients. Isradipine has been approved by the Food and Drug Administration (FDA) to treat high blood pressure but is considered investigational in this study, as it has not been approved for use in patients with PD.Isradipine can affect the function of specialized channels that are present in the types of brain cells that are affected in PD patient. These cells are usually responsible for making dopamine, which is depleted in patients with PD. Isradipine may block the damage caused by the flow of certain chemicals through these channels. Laboratory data has showed that Isradipine may prevent the development of Parkinson-like symptoms in animal studies. Isradipine has been evaluated in some patients with PD. The first study with isradipine controlled release (CR) in patients with early PD and normal blood pressure found that the drug was reasonably well tolerated and safe. The controlled release formulation of isradipine is not available for use and therefore this study is using the immediate release formulation. Eligible participants will be followed for up to 36 months and will be expected to complete 12 in-person visits and 4 telephone visits. The study visits will include clinical assessment of motor, neuropsychiatric and cognitive testing as well as collection of blood and urine samples. Study drug will taken twice daily, in the morning and in the evening with or without food. Prior to taking study drug, study participants will be required to take their blood pressure with a home blood pressure device provided to them for use in this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 336
- Subjects with early idiopathic PD (presence of at least two out of three cardinal manifestations of PD). If tremor is not present, subjects must have unilateral onset and persistent asymmetry of the symptoms
- Age equal or greater than 30 years at the time of diagnosis of PD
- Hoehn and Yahr stage less than or equal to 2
- Diagnosis of PD less than 3 years.
- Currently NOT receiving dopaminergic therapy (levodopa, dopamine agonist or MAO-B inhibitors) and NOT projected to require PD symptomatic therapy for at least 3 months from the baseline visit
- Use of amantadine and/or anticholinergics will be allowed provided that the dose is stable for 8 weeks prior to the baseline visit
- If subject is taking any central nervous system acting medications (e.g., benzodiazepines, antidepressants, hypnotics) regimen must be stable for 30 days prior to the baseline visit
- Women of childbearing potential may enroll but must use a reliable measure of contraception and have a negative serum pregnancy test at the screening visit
- Subjects with a diagnosis of an atypical Parkinsonism
- Subjects unwilling or unable to give informed consent
- Exposure to dopaminergic PD therapy within 60 days prior to baseline visit or for consecutive 3 months or more at any point in the past
- History of clinically significant orthostatic hypotension or presence of orthostatic hypotension at the screening or baseline visit defined as greater than or equal to 20 mmHg change in systolic BP and greater than or equal to 10 mmHg change in diastolic BP from sitting position to standing after 2 minutes, or baseline sitting BP less than 90/60
- History of congestive heart failure
- Clinically significant bradycardia
- Presence of 2nd or 3rd degree atrioventricular block or other significant ECG abnormalities that in the investigator's opinion would compromise participation in study
- Clinically significant abnormalities in the Screening Visit laboratory studies or ECG
- Presence of other known medical or psychiatric comorbidity that in the investigator's opinion would compromise participation in the study
- Prior exposure to isradipine or other dihydropyridine calcium channel blockers within 6 months of the baseline visit
- Subjects on greater than 2 concomitant antihypertensive medications. If a history of hypertension, then a maximum of 2 other antihypertensive agents will be allowed provided that the dosages of concomitant anti HTN therapy can be reduced/adjusted during the study based on the BP readings in consultation with the subject's primary care provider or cardiologist. Use of any concomitant calcium channel blockers will not be allowed from the baseline visit and for the duration of the study
- Use of grapefruit juice, ginkgo biloba, St. John's wort or ginseng will be prohibited starting from the screening visit and for the duration of the study (as they interfere with the metabolism of isradipine)
- Use of clarithromycin, telithromycin and erythromycin will be prohibited starting from the screening visit and for the duration of the study as the combination of clarithromycin, telithromycin or erythromycin and calcium channel blockers has been reported to be associated with increased risk of kidney and heart injury
- Presence of cognitive dysfunction defined by a Montreal Cognitive assessment (MoCA) score of less than 26 at screening
- Subjects with clinically significant depression as determined by a Beck Depression Inventory II (BDI) score greater than 15 at the screening visit
- History of exposure to typical or atypical antipsychotics or other dopamine blocking agents within 6 months prior to the baseline visit
- History of use of an investigational drug within 30 days prior to the screening visit
- History of brain surgery for PD
- Allergy/sensitivity to isradipine or its matching placebo or their formulations
- Pregnant or lactating woman
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Isradipine Isradipine Oral capsule of up to 5 mg of isradipine taken twice daily for 36 months. Placebo (for Isradipine) Placebo (for Isradipine) Oral capsule taken twice daily for 36 months.
- Primary Outcome Measures
Name Time Method Adjusted Mean Change in Total Unified Parkinson Disease Rating Scale (UPDRS) Score Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the total (Part I-III) UPDRS score in the active treatment arm versus placebo between the baseline and 36 month visit. The change of UPDRS ranges from -30 to 80, larger value shows more disability from PD.
Adjusted Mean Change in Adjusted UPDRS Score Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the adjusted UPDRS Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change of adjusted UPDRS ranges from -100 to 150, larger value shows more disability from PD.
- Secondary Outcome Measures
Name Time Method Adjusted Mean Change in UPDRS Part IV Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part IV in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part IV ranges from -10 to 10, larger value shows more disability from PD.
Adjusted Mean Change in Modified Rankin Score Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Modified Rankin Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Modified Rankin Score ranges from -1 to 3, larger value shows worsening of conditions.
Adjusted Mean Change in MoCA Score Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MoCA Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MoCA Score ranges from -10 to 6, larger value shows improvement of conditions.
Adjusted Mean Change in PDQ39 Total Score Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the PDQ39 Total Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in PDQ39 Total Score ranges from -16 to 44, larger value shows worsening of conditions.
Adjusted Mean Change in BDI Total Score Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the BDI Total Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in BDI Total Score ranges from -9 to 22, larger value shows worsening of conditions.
Risk of Need for Dyskinesia Baseline to 36 months of treatment Number of participants with need for Dyskinesia Therapy.
Risk of Need for Fluctuations Baseline to 36 months of treatment Number of participants with need for Fluctuations Therapy.
Adjusted Mean Change in UPDRS Score to 1 Year Baseline to 12 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS nmEDL(Non-Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 12 month visit. The change of UPDRS ranges from -22 to 23, larger value shows more disability from PD.
Adjusted Mean Change in LED Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the LED(levodopa equivalent dose) in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED ranges from -100 to 3000, larger value shows more disability from PD.
Adjusted Mean Change in LED Cumulative Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the LED(levodopa equivalent dose) cumulative in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED cumulative ranges from 0 to 1200000, larger value shows more disability from PD.
Adjusted Mean Change in UPDRS Part III OFF Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part III OFF rating in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part III OFF ranges from -30 to 100, larger value shows more disability from PD.
Adjusted Mean Change in MDS-UPDRS nmEDL Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS nmEDL(Non-Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MDS-UPDRS nmEDL ranges from -6 to 10, larger value shows more disability from PD.
Adjusted Mean Change in MDS-UPDRS mEDL Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS mEDL(Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MDS-UPDRS mEDL ranges from -8 to 35, larger value shows more disability from PD.
Adjusted Mean Change in UPDRS Part II Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part II (ADL Function) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part II ranges from -12 to 19, larger value shows more disability from PD.
Adjusted Mean Change in SE/ADL Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the SE/ADL in the active treatment arm versus placebo between the baseline and 36 month visit. The change of UPDRS ranges from -70 to 20, larger value shows improvement of PD.
Adjusted Mean Change in Ambulatory Capacity Baseline to 36 months of treatment Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Ambulatory Capacity in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Ambulatory Capacity ranges from -4 to 12, larger value shows worsening of conditions.
Risk of Need for Antiparkinsonian Therapy Baseline to 36 months of treatment Number of participants with need for Antiparkinsonian Therapy.
Trial Locations
- Locations (54)
University of California
🇺🇸Irvine, California, United States
University of Rochester
🇺🇸Rochester, New York, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Rocky Mountain Movement Disorders Center
🇺🇸Englewood, Colorado, United States
Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
LSU Health Science Center
🇺🇸Shreveport, Louisiana, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
CHUM - Hopital Notre-Dame
🇨🇦Montreal, Quebec, Canada
Struthers Parkinson's Center
🇺🇸Golden Valley, Minnesota, United States
Toronto Western Hospital, University Health Network
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Affilie
🇨🇦Quebec City, Quebec, Canada
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
The Centre for Addiction and Mental Health
🇨🇦Toronto, Ontario, Canada
The Parkinsons & Movement Disorder Institute
🇺🇸Fountain Valley, California, United States
Banner Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
Michigan State University
🇺🇸East Lansing, Michigan, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Atlantic Neuroscience Institute
🇺🇸Summit, New Jersey, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Weill Medical College of Cornell University
🇺🇸New York, New York, United States
Sentara Neurology Specialists
🇺🇸Virginia Beach, Virginia, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
University of Calgary
🇨🇦Calgary, Alberta, Canada
Booth Gardner Parkinson's Care Center
🇺🇸Kirkland, Washington, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Albany Medical College
🇺🇸Albany, New York, United States
Health Quest Kingston
🇺🇸Kingston, New York, United States
Ottawa Hospital Civic Site
🇨🇦Ottawa, Ontario, Canada
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Texas Health Science Center
🇺🇸Houston, Texas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of California San Diego
🇺🇸San Diego, California, United States
Institute of Neurodegenerative Disorders
🇺🇸New Haven, Connecticut, United States
University of Miami
🇺🇸Miami, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Nevada School of Medicine
🇺🇸Las Vegas, Nevada, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
University of South Florida
🇺🇸Tampa, Florida, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Pacific Health Research & Education Institute
🇺🇸Honolulu, Hawaii, United States