Efficacy of Isradipine in Early Parkinson Disease

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ClinicalTrials.gov Identifier: NCT02168842

Recruitment Status : Completed

First Posted : June 20, 2014

Results First Posted : January 14, 2020

Last Update Posted : January 14, 2020

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

National Institute of Neurological Disorders and Stroke (NINDS)

Michael J. Fox Foundation for Parkinson's Research

The Parkinson Study Group

Information provided by (Responsible Party):

Robert Holloway, University of Rochester

Study Description

Brief Summary:

The purpose of the study is to determine whether treatment with isradipine is effective in slowing the progression of Parkinson disease disability.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Drug: Isradipine Drug: Placebo (for Isradipine)	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	336 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	Phase 3 Double-blind Placebo-controlled Parallel Group Study of Isradipine as a Disease Modifying Agent in Subjects With Early Parkinson Disease
Actual Study Start Date :	November 2014
Actual Primary Completion Date :	November 2018
Actual Study Completion Date :	November 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Parkinson disease

MedlinePlus related topics: Parkinson's Disease

Drug Information available for: Isradipine

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Isradipine Oral capsule of up to 5 mg of isradipine taken twice daily for 36 months.	Drug: Isradipine Oral capsules Isradipine IR, up to 10 mg, taken twice daily
Placebo Comparator: Placebo (for Isradipine) Oral capsule taken twice daily for 36 months.	Drug: Placebo (for Isradipine) Sugar Pill manufactured to look like Isradipine but has no active ingredients

Outcome Measures

Primary Outcome Measures :

Adjusted Mean Change in Total Unified Parkinson Disease Rating Scale (UPDRS) Score [ Time Frame: 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 [ Time Frame: 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 :

Adjusted Mean Change in LED [ Time Frame: 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 [ Time Frame: 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 IV [ Time Frame: 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 MDS-UPDRS nmEDL [ Time Frame: 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 [ Time Frame: 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 Score to 1 Year [ Time Frame: 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 UPDRS Part II [ Time Frame: 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 UPDRS Part III OFF [ Time Frame: 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 SE/ADL [ Time Frame: 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 Modified Rankin Score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Ambulatory Capacity [ Time Frame: 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.
Adjusted Mean Change in BDI Total Score [ Time Frame: 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 Antiparkinsonian Therapy [ Time Frame: Baseline to 36 months of treatment ]
Number of participants with need for Antiparkinsonian Therapy.
Risk of Need for Dyskinesia [ Time Frame: Baseline to 36 months of treatment ]
Number of participants with need for Dyskinesia Therapy.
Risk of Need for Fluctuations [ Time Frame: Baseline to 36 months of treatment ]
Number of participants with need for Fluctuations Therapy.

Other Outcome Measures:

Adjusted Mean Change in UPDRS PIGD Score [ Time Frame: 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 PIGD Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS PIGD Score ranges from -1 to 3, larger value shows worsening of conditions.
Adjusted Mean Change in UPDRS Tremor Score [ Time Frame: 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 Tremor Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Tremor Score ranges from -1 to 2, larger value shows worsening of conditions.
Adjusted Mean Change in H/Y Stage [ Time Frame: Baseline to 36 months of treatment ]
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the H/Y Stage in the active treatment arm versus placebo between the baseline and 36 month visit. The change in H/Y Stage ranges from -1 to 3, larger value shows worsening of conditions.
Adjusted Mean Change in Levodopa [ Time Frame: Baseline to 36 months of treatment ]
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Levodopa in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED ranges from -200 to 2000, larger value shows more disability from PD.
Adjusted Mean Change in Levodopa Cumulative [ Time Frame: Baseline to 36 months of treatment ]
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Levodopa Cumulative in the active treatment arm versus placebo between the baseline and 36 month visit. The change of Levodopa cumulative ranges from 0 to 800000, larger value shows more disability from PD.
Adjusted Mean Change in Systolic BP, Seated [ Time Frame: Baseline to 36 months of treatment ]
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Systolic BP, Seated in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Systolic BP, Seated ranges from -65 to 50. larger value shows worsening of conditions.
Adjusted Mean Change in Diastolic BP, Seated [ Time Frame: Baseline to 36 months of treatment ]
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Diastolic BP, Seated in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Diastolic BP, Seated ranges from -35 to 25. larger value shows worsening of conditions.

Eligibility Criteria

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Ages Eligible for Study:	30 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02168842

Locations

Show 54 study locations

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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
Banner Sun Health Research Institute
Sun City, Arizona, United States, 85315
United States, California
The Parkinsons & Movement Disorder Institute
Fountain Valley, California, United States, 92708
University of California
Irvine, California, United States, 92697
University of California San Diego
San Diego, California, United States, 92093
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Colorado
Rocky Mountain Movement Disorders Center
Englewood, Colorado, United States, 80113
United States, Connecticut
Institute of Neurodegenerative Disorders
New Haven, Connecticut, United States, 06510
United States, Florida
University of Miami
Miami, Florida, United States, 33136
University of South Florida
Tampa, Florida, United States, 33613
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30329
United States, Hawaii
Pacific Health Research & Education Institute
Honolulu, Hawaii, United States, 96819
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Kentucky
University of Kentucky Medical Center
Lexington, Kentucky, United States, 40536
United States, Louisiana
LSU Health Science Center
Shreveport, Louisiana, United States, 71103
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Boston University Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Michigan State University
East Lansing, Michigan, United States, 48824
United States, Minnesota
Struthers Parkinson's Center
Golden Valley, Minnesota, United States, 55427
University of Minnesota
Minneapolis, Minnesota, United States, 55414
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Nevada
University of Nevada School of Medicine
Las Vegas, Nevada, United States, 89102
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Atlantic Neuroscience Institute
Summit, New Jersey, United States, 07901
United States, New York
Albany Medical College
Albany, New York, United States, 12208
Health Quest Kingston
Kingston, New York, United States, 12401
Columbia University Medical Center
New York, New York, United States, 10032
Weill Medical College of Cornell University
New York, New York, United States, 20021
University of Rochester
Rochester, New York, United States, 14618
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Ohio State University
Columbus, Ohio, United States, 43221
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29401
United States, Texas
University of Texas Health Science Center
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84108
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22903
Sentara Neurology Specialists
Virginia Beach, Virginia, United States, 23456
United States, Washington
Booth Gardner Parkinson's Care Center
Kirkland, Washington, United States, 98034
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 4Z6
University of Alberta Hospital
Edmonton, Alberta, Canada, t6g 2g3
Canada, Ontario
Ottawa Hospital Civic Site
Ottawa, Ontario, Canada, K1Y 4E9
The Centre for Addiction and Mental Health
Toronto, Ontario, Canada, m3b 2s7
Toronto Western Hospital, University Health Network
Toronto, Ontario, Canada, M5T 2S8
Canada, Quebec
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
Centre Hospitalier Affilie
Quebec City, Quebec, Canada, G1J 1Z4

Sponsors and Collaborators

University of Rochester

National Institute of Neurological Disorders and Stroke (NINDS)

Michael J. Fox Foundation for Parkinson's Research

The Parkinson Study Group

Investigators

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Principal Investigator:	Tanya Simuni, MD	Northwestern University
Principal Investigator:	Robert Holloway, MD MPH	University of Rochester

Study Documents (Full-Text)

Documents provided by Robert Holloway, University of Rochester:

Study Protocol [PDF] August 31, 2016

Statistical Analysis Plan [PDF] December 1, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Venuto CS, Yang L, Javidnia M, Oakes D, James Surmeier D, Simuni T. Isradipine plasma pharmacokinetics and exposure-response in early Parkinson's disease. Ann Clin Transl Neurol. 2021 Mar;8(3):603-612. doi: 10.1002/acn3.51300. Epub 2021 Jan 18.

Parkinson Study Group STEADY-PD III Investigators. Isradipine Versus Placebo in Early Parkinson Disease: A Randomized Trial. Ann Intern Med. 2020 May 5;172(9):591-598. doi: 10.7326/M19-2534. Epub 2020 Mar 31.

McFarthing K, Simuni T. Clinical Trial Highlights: Phase III Study in Spotlight. J Parkinsons Dis. 2019;9(1):3-4. doi: 10.3233/JPD-190002. No abstract available.

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Responsible Party:	Robert Holloway, Principal Investigator, University of Rochester
ClinicalTrials.gov Identifier:	NCT02168842
Other Study ID Numbers:	STEADY-PD III U01NS080818-01A1 ( U.S. NIH Grant/Contract ) U01NS080840-01A1 ( U.S. NIH Grant/Contract )
First Posted:	June 20, 2014 Key Record Dates
Results First Posted:	January 14, 2020
Last Update Posted:	January 14, 2020
Last Verified:	January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Robert Holloway, University of Rochester:


Parkinson Parkinson Disease Parkinson's Disease

Additional relevant MeSH terms:

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Parkinson Disease Parkinsonian Disorders Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Movement Disorders Synucleinopathies Neurodegenerative Diseases	Isradipine Antihypertensive Agents Calcium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Calcium-Regulating Hormones and Agents Physiological Effects of Drugs Vasodilator Agents

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