Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 3 Double-blind Placebo-controlled Parallel Group Study of Isradipine as a Disease Modifying Agent in Subjects With Early Parkinson Disease
Brief Summary: The purpose of the study is to determine whether treatment with isradipine is effective in slowing the progression of Parkinson disease disability.


Options:
A: Inclusion Criteria:

* Clinical diagnosis of idiopathic PD
* Able to provide informed consent
* Ability to ambulate ≥ 300ft with or without an assistive device
* Hoehn and Yahr stage 2-4

Exclusion Criteria:

* Undergone any surgical procedure for the treatment of PD, such as deep brain stimulation
* Those who are considered to be high risk exercisers per American College of Sports Medicine exercise screening questionnaire
* Musculoskeletal injury or neurological injury other than PD that would restrict physical activity
* Inability to follow 2 step commands
* Significant cognitive impairment as designated by ≥ 3 errors on the Short Portable Mental Status Questionnaire
B: Inclusion Criteria:

* Clinical diagnosis of primary Parkinson's disease
* In a Hoehn and Yahr stage less than stage III
* Disease duration is less than 5 years
* Not likely to require dopaminergic therapy within 6 months

Exclusion Criteria:

* Use of any PD medication within 60 days prior to the beginning the study, including levodopa, direct dopamine agonists, amantadine, Rasagiline (Azilect), Selegiline (Eldepryl), Artane (trihexyphenidyl).
* Duration of previous use of medications for PD that exceeds 90 days
* Expected to require dopaminergic therapy in the next 6 months
* Poorly controlled or unstable cardiovascular disease
* Uncontrolled hypertension
* Hypo- or hyperthyroidism, abnormal liver function, abnormal renal function
* Mild cognitive impairment (Montreal Cognitive Assessment score\<26/30)
* Depression that precludes ability to exercise (Beck depression score\>13)
* Disorders that interfere with ability to perform endurance exercises
* Regular participation in vigorous endurance exercise
* Evidence of serious arrhythmias or ischemic heart disease
* Any clinically significant medical condition, psychiatric condition, drug or alcohol abuse, or laboratory abnormality that would, in the judgment of the investigators, interfere with the ability to participate in the study
C: Inclusion Criteria:

* Idiopathic Parkinson's Disease (PD) diagnosed between the ages of 30 and 85 years;
* Hoehn and Yahr Stage 1-3 in an "on" state;
* Require levodopa-containing medication regimen at least 3 times during the waking day;
* Experience motor fluctuations with a minimum of 2 hours of average daily "off" time per waking day (excluding early morning "off" time) and demonstrate levodopa responsiveness;
* Are on stable PD medication regimen;
* Total daily LD dose \<1600 mg/day;
* Able to perform a spirometry maneuver in the ON and OFF states;
* Normal cognition confirmed by MMSE score ≥25

Exclusion Criteria:

* Pregnant or lactating females;
* Previous surgery for PD or plan to have stereotactic surgery during the study period;
* History of psychotic symptoms requiring treatment, or suicide ideation or attempt within last year;
* Known contraindication to the use of levodopa;
* Any significant condition, severe concurrent disease, abnormality or finding that would make patients unsuitable or may compromise patient safety;
* Any contraindication to performing routine spirometry.
D: 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

Answer: D