Efficacy of Isradipine in Early Parkinson Disease

NCT ID: NCT02168842

Last Updated: 2020-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 336 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2018-11-30

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.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Isradipine

Oral capsule of up to 5 mg of isradipine taken twice daily for 36 months.

Group Type: ACTIVE_COMPARATOR

Isradipine

Intervention Type: DRUG

Oral capsules Isradipine IR, up to 10 mg, taken twice daily

Placebo (for Isradipine)

Oral capsule taken twice daily for 36 months.

Group Type: PLACEBO_COMPARATOR

Placebo (for Isradipine)

Intervention Type: DRUG

Sugar Pill manufactured to look like Isradipine but has no active ingredients

Interventions

Isradipine

Oral capsules Isradipine IR, up to 10 mg, taken twice daily

Intervention Type: DRUG

Placebo (for Isradipine)

Sugar Pill manufactured to look like Isradipine but has no active ingredients

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

The Parkinson Study Group

NETWORK

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Robert Holloway

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tanya Simuni, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Robert Holloway, MD MPH

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Banner Sun Health Research Institute

Sun City, Arizona, United States

The Parkinsons & Movement Disorder Institute

Fountain Valley, California, United States

University of California

Irvine, California, United States

University of California San Diego

San Diego, California, United States

University of California, San Francisco

San Francisco, California, United States

Rocky Mountain Movement Disorders Center

Englewood, Colorado, United States

Institute of Neurodegenerative Disorders

New Haven, Connecticut, United States

University of Miami

Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Pacific Health Research & Education Institute

Honolulu, Hawaii, United States

Northwestern University

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Kentucky Medical Center

Lexington, Kentucky, United States

LSU Health Science Center

Shreveport, Louisiana, United States

University of Maryland

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Boston University Medical Center

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Michigan State University

East Lansing, Michigan, United States

Struthers Parkinson's Center

Golden Valley, Minnesota, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University

St Louis, Missouri, United States

Nebraska Medical Center

Omaha, Nebraska, United States

University of Nevada School of Medicine

Las Vegas, Nevada, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Atlantic Neuroscience Institute

Summit, New Jersey, United States

Albany Medical College

Albany, New York, United States

Health Quest Kingston

Kingston, New York, United States

Columbia University Medical Center

New York, New York, United States

Weill Medical College of Cornell University

New York, New York, United States

University of Rochester

Rochester, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Texas Health Science Center

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

University of Virginia

Charlottesville, Virginia, United States

Sentara Neurology Specialists

Virginia Beach, Virginia, United States

Booth Gardner Parkinson's Care Center

Kirkland, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

University of Calgary

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

Ottawa Hospital Civic Site

Ottawa, Ontario, Canada

The Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Toronto Western Hospital, University Health Network

Toronto, Ontario, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

Centre Hospitalier Affilie

Québec, Quebec, Canada

Countries

United States; Canada

References

Di Luca DG, Macklin EA, Hodgeman K, Lopez G, Pothier L, Callahan KF, Lowell J, Chan J, Videnovic A, Lungu C, Lang AE, Litvan I, Schwarzschild MA, Simuni T. Enrollment of Participants From Marginalized Racial and Ethnic Groups: A Comparative Assessment of the STEADY-PD III and SURE-PD3 Trials. Neurol Clin Pract. 2023 Feb;13(1):e200113. doi: 10.1212/CPJ.0000000000200113. Epub 2023 Jan 18.

Reference Type: DERIVED

PMID: 36865634 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33460320 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32227247 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30741695 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U01NS080818-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01NS080840-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STEADY-PD III

Identifier Type: -

Identifier Source: org_study_id