Efficacy of Isradipine in Early Parkinson Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02168842
• Date of registration: 18/06/2014
• Prospective Registration: Yes
• Primary sponsor: University of Rochester
• Public title: Efficacy of Isradipine in Early Parkinson Disease
• Scientific title: Phase 3 Double-blind Placebo-controlled Parallel Group Study of Isradipine as a Disease Modifying Agent in Subjects With Early Parkinson Disease
• Date of first enrolment: November 2014
• Target sample size: 336
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02168842
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Canada, United States

Contacts

• Name: Tanya Simuni, MD
• Affiliation: Northwestern University

• Name: Robert Holloway, MD MPH
• Affiliation: University of Rochester

Key inclusion & exclusion 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



Age minimum: 30 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Intervention(s)

Drug: Placebo (for Isradipine)

Drug: Isradipine

Primary Outcome(s)

Adjusted Mean Change in Adjusted UPDRS Score [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in Total Unified Parkinson Disease Rating Scale (UPDRS) Score [Time Frame: Baseline to 36 months of treatment]

Secondary Outcome(s)

Adjusted Mean Change in LED Cumulative [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in UPDRS Part III OFF [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in MoCA Score [Time Frame: Baseline to 36 months of treatment]

Risk of Need for Fluctuations [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in Ambulatory Capacity [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in MDS-UPDRS mEDL [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in PDQ39 Total Score [Time Frame: Baseline to 36 months of treatment]

Risk of Need for Antiparkinsonian Therapy [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in SE/ADL [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in UPDRS Part IV [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in LED [Time Frame: Baseline to 36 months of treatment]

Risk of Need for Dyskinesia [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in BDI Total Score [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in MDS-UPDRS nmEDL [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in UPDRS Score to 1 Year [Time Frame: Baseline to 12 months of treatment]

Adjusted Mean Change in Modified Rankin Score [Time Frame: Baseline to 36 months of treatment]

Adjusted Mean Change in UPDRS Part II [Time Frame: Baseline to 36 months of treatment]

Secondary ID(s)

U01NS080840-01A1

U01NS080818-01A1

STEADY-PD III

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Neurological Disorders and Stroke (NINDS)

Michael J. Fox Foundation for Parkinson's Research

The Parkinson Study Group

Results

• Results available: Yes
• Date Posted: 14/01/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02168842