Efficacy of Isradipine in Early Parkinson Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: Isradipine; Placebo (for Isradipine)
Intervention description: Oral capsules Isradipine IR, up to 10 mg, taken twice daily; Sugar Pill manufactured to look like Isradipine but has no active ingredients
Intervention MeSH terms: Isradipine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 336.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: Parkinson; Parkinson Disease; Parkinson's Disease

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

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