Clinical trial NCT00909545: Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease
Official title: A Pilot Phase II Double-Blind, Placebo-Controlled, Tolerability and Dosage Finding Study of Isradipine CR as a Disease Modifying Agent in Patients With Early Parkinson Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Keywords: Early Parkinson disease
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
name: Northwestern University Dixon Fund
name: The Parkinson Study Group
First posted: 2009-05-28
Enrollment: 99
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to establish a dosage of isradipine CR that is tolerable and demonstrates preliminary efficacy for utilization in future pivotal efficacy studies.

Detailed description: There is solid scientific rational and preclinical data supporting a clinical trial of isradipine CR as a potential disease modifying agent in early PD. Human pharmacokinetic data demonstrate that it is feasible to achieve the serum concentrations in humans that were neuroprotective in preclinical models with the FDA approved dosage range. Pilot data demonstrate acceptable tolerability of isradipine CR in the PD population. Tolerability is inversely proportional to the dosage dependent. Considering that tolerability of isradipine CR is inversely proportional to the dosage exposure, it is essential to proceed with the dose selection tolerability study in preparation for the future efficacy trials.

The tolerability, defined as the ability to complete the study, of three dosages of isradipine CR relative to placebo in subjects with early Parkinson's disease will be examined first. The dosage that is tolerable and demonstrates preliminary efficacy will be evaluated further in the future pivotal efficacy studies.

Eligibility criteria: Inclusion Criteria:

* Subjects with early idiopathic PD. If tremor is not present, subjects must have unilateral onset and persistent asymmetry of the symptoms.
* Be over 30 years old at the time of diagnosis of PD.
* Hoehn \& Yahr stage is less than or equal to 2.5.
* Currently not receiving dopaminergic therapy and not projected to require dopaminergic therapy for at least 6 months from enrollment.
* Use of MAO-B inhibitors (rasagiline, selegiline), amantadine, or anticholinergics will be allowed. The dosage has to be stable for 3 months prior to baseline visit and throughout the duration of the study.

Exclusion Criteria:

* Subjects with a diagnosis of an atypical Parkinsonism
* Subjects unwilling or unable to give informed consent
* Use of CoQ10 at a dosage \>600mg daily or use of creatine \>5 grams daily within the 60 days prior to randomization
* Exposure to dopaminergic PD therapy within 60 days prior to enrollment or for 3 months or more at any point in the past
* History of clinically significant orthostatic hypotension or presence of orthostatic hypotension at the screening visit defined as \> 20 mmHg change in systolic BP and \>10mm change in diastolic BP after 2 min of standing, or baseline BP \<90/60
* History of congestive heart failure
* History of bradycardia defined as heart rate \<55
* 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 electrocardiogram.
* 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 calcium channel blockers within 6 months of baseline
* Subjects with history of hypertension treated with a maximum of 2 other antihypertensive agents will be allowed provided that the doses 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 physician or cardiologist.
* Use of grapefruit juice, Ginkgo biloba, St. John's wart and/or ginseng will be prohibited during the study (as they interfere with the metabolism of isradipine).
* Presence of cognitive dysfunction defined by a Mini Mental Status Exam ( MMSE) score \< 26 at screening
* Subjects with clinically significant depression as determined by a Beck Depression Inventory (BDI) score \>15 at screening
* History of exposure to typical or atypical antipsychotics or other dopamine blocking agents within 6 months prior to enrollment
* Subjects have to be on a stable regimen of central nervous system acting medications (benzodiazepines, antidepressants, hypnotics) for 30 days prior to enrollment
* Lactating women or women of childbearing potential who are not surgically sterilized have to use a reliable measure of contraception and have a negative serum pregnancy test at screening
* Participation in other investigational drug trials within 30 days prior to screening
* History of brain surgery for PD

Primary outcomes:
measure: Tolerability of the Three Dosages(5mg, 10mg and 20mg) of Isradipine CR.
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
Secondary outcomes:
measure: Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS)
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Efficacy: Change in Activities of Daily Living(ADL) Subscale of the Unified Parkinson's Disease Rating Scale
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Efficacy: Change in Modified Hoehn & Yahr Scale
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Efficacy: Change in Modified Schwab & England Independence Scale
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Efficacy: Change in Beck Depression Inventory II (BDI-II)
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Efficacy: Change in Montreal Cognitive Assessment
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Efficacy: Change in Parkinson Disease Quality of Life Questionnaire-39(PDQ-39)
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Vital Signs: Change in Systolic Standing
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Vital Signs: Change in Systolic Supine
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Vital Signs: Change in Diastolic Standing
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Vital Signs: Change in Diastolic Supine
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Vital Signs: Change in Pulse Standing
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Vital Signs: Change in Pulse Supine
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Oedema Peripheral
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Dizziness
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Nasopharyngitis
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Headache
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Constipation
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Fatigue
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Nausea
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Upper Respiratory Tract Infection
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Depression
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Somnolence
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Insomnia
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Dyspepsia
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Diarrhoea
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Sinusitis
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Back Pain
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
measure: Common Adverse Events: Hypotension
timeFrame: Baseline to 12 months or the time to require dopaminergic therapy
Other outcomes:
Locations:
city: Sunnyvale
country: United States
facility: Parkinson Institute
state: California
city: New Haven
country: United States
facility: Institute for Neurodegenerative Disorders
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: University of South Flordia
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Honolulu
country: United States
facility: Pacific Health Institute
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Golden Valley
country: United States
facility: Park Nicolet Clinic
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
city: Ottawa
country: Canada
facility: Ottowa Hospital Civic Site
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
Study officials:
affiliation: Northwestern University
name: Tanya Simuni, MS
role: STUDY_CHAIR
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