Efficacy of Isradipine in Early Parkinson Disease

NCT02168842 | Completed Phase 3 Results DMC

• 3 other identifiers: STEADY-PD IIIU01NS080818-01A1U01NS080840-01A1
• Study Type: interventional
• Target: 336
• Locations: 2 countries
• Sites: 54

Brief Summary

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

Conditions

Parkinson Disease

Keywords

Parkinson; Parkinson Disease; Parkinson's Disease

Outcome Measures

Primary Outcomes (2)

• Adjusted Mean Change in Total Unified Parkinson Disease Rating Scale (UPDRS) Score

  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.

  Baseline to 36 months of treatment

• Adjusted Mean Change in Adjusted UPDRS Score

  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.

  Baseline to 36 months of treatment

Secondary Outcomes (17)

• Adjusted Mean Change in LED

  Baseline to 36 months of treatment

• Adjusted Mean Change in LED Cumulative

  Baseline to 36 months of treatment

• Adjusted Mean Change in UPDRS Part IV

  Baseline to 36 months of treatment

• Adjusted Mean Change in MDS-UPDRS nmEDL

  Baseline to 36 months of treatment

• Adjusted Mean Change in MDS-UPDRS mEDL

  Baseline to 36 months of treatment

Other Outcomes (7)

• Adjusted Mean Change in UPDRS PIGD Score

  Baseline to 36 months of treatment

• Adjusted Mean Change in UPDRS Tremor Score

  Baseline to 36 months of treatment

• Adjusted Mean Change in H/Y Stage

  Baseline to 36 months of treatment

Study Arms (2)

Isradipine

ACTIVE COMPARATOR

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

Drug: Isradipine

Placebo (for Isradipine)

PLACEBO COMPARATOR

Oral capsule taken twice daily for 36 months.

Drug: Placebo (for Isradipine)

Interventions

Isradipine DRUG

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

Isradipine

Placebo (for Isradipine) DRUG

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

Placebo (for Isradipine)

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Rochester: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Michael J. Fox Foundation for Parkinson's Research: collaborator
• The Parkinson Study Group: collaborator

Study Sites (54)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85315, United States

Location

The Parkinsons & Movement Disorder Institute

Fountain Valley, California, 92708, United States

Location

University of California

Irvine, California, 92697, United States

Location

University of California San Diego

San Diego, California, 92093, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Rocky Mountain Movement Disorders Center

Englewood, Colorado, 80113, United States

Location

Institute of Neurodegenerative Disorders

New Haven, Connecticut, 06510, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

Pacific Health Research & Education Institute

Honolulu, Hawaii, 96819, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

LSU Health Science Center

Shreveport, Louisiana, 71103, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Struthers Parkinson's Center

Golden Valley, Minnesota, 55427, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

University of Nevada School of Medicine

Las Vegas, Nevada, 89102, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Atlantic Neuroscience Institute

Summit, New Jersey, 07901, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Health Quest Kingston

Kingston, New York, 12401, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Weill Medical College of Cornell University

New York, New York, 20021, United States

Location

University of Rochester

Rochester, New York, 14618, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29401, United States

Location

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Sentara Neurology Specialists

Virginia Beach, Virginia, 23456, United States

Location

Booth Gardner Parkinson's Care Center

Kirkland, Washington, 98034, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, t6g 2g3, Canada

Location

Ottawa Hospital Civic Site

Ottawa, Ontario, K1Y 4E9, Canada

Location

The Centre for Addiction and Mental Health

Toronto, Ontario, m3b 2s7, Canada

Location

Toronto Western Hospital, University Health Network

Toronto, Ontario, M5T 2S8, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Centre Hospitalier Affilie

Québec, Quebec, G1J 1Z4, Canada

Location

Related Publications (4)

• 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.

  PMID: 36865634 DERIVED

• 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.

  PMID: 33460320 DERIVED

• 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.

  PMID: 32227247 DERIVED

• 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.

  PMID: 30741695 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Isradipine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: David Oakes, PhD
• Organization: University of Rochester Medical Center, Department of Biostatistics and Computational Biology

david_oakes@urmc.rochester.edu

5852752405

Study Officials

• Tanya Simuni, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

• Robert Holloway, MD MPH

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 18, 2014
• First Posted: June 20, 2014
• Study Start: November 1, 2014
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: January 14, 2020
• Results First Posted: January 14, 2020

Record last verified: 2020-01

Locations

US (47); CA (7)