Parkinson Disease
Conditions
Keywords
Parkinson, Parkinson Disease, Parkinson's 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.
Detailed description
The study will enroll 336 participants in this multi-center study at approximately 56 sites across the US and Canada. In this study, we are comparing 10 mg of Isradipine to Placebo for treatment of newly diagnosed PD patients. Isradipine has been approved by the Food and Drug Administration (FDA) to treat high blood pressure but is considered investigational in this study, as it has not been approved for use in patients with PD.Isradipine can affect the function of specialized channels that are present in the types of brain cells that are affected in PD patient. These cells are usually responsible for making dopamine, which is depleted in patients with PD. Isradipine may block the damage caused by the flow of certain chemicals through these channels. Laboratory data has showed that Isradipine may prevent the development of Parkinson-like symptoms in animal studies. Isradipine has been evaluated in some patients with PD. The first study with isradipine controlled release (CR) in patients with early PD and normal blood pressure found that the drug was reasonably well tolerated and safe. The controlled release formulation of isradipine is not available for use and therefore this study is using the immediate release formulation. Eligible participants will be followed for up to 36 months and will be expected to complete 12 in-person visits and 4 telephone visits. The study visits will include clinical assessment of motor, neuropsychiatric and cognitive testing as well as collection of blood and urine samples. Study drug will taken twice daily, in the morning and in the evening with or without food. Prior to taking study drug, study participants will be required to take their blood pressure with a home blood pressure device provided to them for use in this study.
Interventions
DRUGIsradipine
Oral capsules Isradipine IR, up to 10 mg, taken twice daily
DRUGPlacebo (for Isradipine)
Sugar Pill manufactured to look like Isradipine but has no active ingredients
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Michael J. Fox Foundation for Parkinson's Research
The Parkinson Study Group
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change in Total Unified Parkinson Disease Rating Scale (UPDRS) Score | Baseline to 36 months of treatment | 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. |
| Adjusted Mean Change in Adjusted UPDRS Score | Baseline to 36 months of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change in UPDRS Part II | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part II (ADL Function) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part II ranges from -12 to 19, larger value shows more disability from PD. |
| Adjusted Mean Change in MoCA Score | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MoCA Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MoCA Score ranges from -10 to 6, larger value shows improvement of conditions. |
| Adjusted Mean Change in PDQ39 Total Score | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the PDQ39 Total Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in PDQ39 Total Score ranges from -16 to 44, larger value shows worsening of conditions. |
| Adjusted Mean Change in Ambulatory Capacity | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Ambulatory Capacity in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Ambulatory Capacity ranges from -4 to 12, larger value shows worsening of conditions. |
| Adjusted Mean Change in BDI Total Score | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the BDI Total Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in BDI Total Score ranges from -9 to 22, larger value shows worsening of conditions. |
| Risk of Need for Antiparkinsonian Therapy | Baseline to 36 months of treatment | Number of participants with need for Antiparkinsonian Therapy. |
| Risk of Need for Dyskinesia | Baseline to 36 months of treatment | Number of participants with need for Dyskinesia Therapy. |
| Risk of Need for Fluctuations | Baseline to 36 months of treatment | Number of participants with need for Fluctuations Therapy. |
| Adjusted Mean Change in LED | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the LED(levodopa equivalent dose) in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED ranges from -100 to 3000, larger value shows more disability from PD. |
| Adjusted Mean Change in LED Cumulative | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the LED(levodopa equivalent dose) cumulative in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED cumulative ranges from 0 to 1200000, larger value shows more disability from PD. |
| Adjusted Mean Change in UPDRS Part IV | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part IV in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part IV ranges from -10 to 10, larger value shows more disability from PD. |
| Adjusted Mean Change in MDS-UPDRS nmEDL | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS nmEDL(Non-Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MDS-UPDRS nmEDL ranges from -6 to 10, larger value shows more disability from PD. |
| Adjusted Mean Change in MDS-UPDRS mEDL | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS mEDL(Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MDS-UPDRS mEDL ranges from -8 to 35, larger value shows more disability from PD. |
| Adjusted Mean Change in UPDRS Score to 1 Year | Baseline to 12 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS nmEDL(Non-Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 12 month visit. The change of UPDRS ranges from -22 to 23, larger value shows more disability from PD. |
| Adjusted Mean Change in UPDRS Part III OFF | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part III OFF rating in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part III OFF ranges from -30 to 100, larger value shows more disability from PD. |
| Adjusted Mean Change in SE/ADL | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the SE/ADL in the active treatment arm versus placebo between the baseline and 36 month visit. The change of UPDRS ranges from -70 to 20, larger value shows improvement of PD. |
| Adjusted Mean Change in Modified Rankin Score | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Modified Rankin Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Modified Rankin Score ranges from -1 to 3, larger value shows worsening of conditions. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change in Levodopa | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Levodopa in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED ranges from -200 to 2000, larger value shows more disability from PD. |
| Adjusted Mean Change in Levodopa Cumulative | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Levodopa Cumulative in the active treatment arm versus placebo between the baseline and 36 month visit. The change of Levodopa cumulative ranges from 0 to 800000, larger value shows more disability from PD. |
| Adjusted Mean Change in Systolic BP, Seated | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Systolic BP, Seated in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Systolic BP, Seated ranges from -65 to 50. larger value shows worsening of conditions. |
| Adjusted Mean Change in Diastolic BP, Seated | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Diastolic BP, Seated in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Diastolic BP, Seated ranges from -35 to 25. larger value shows worsening of conditions. |
| Adjusted Mean Change in UPDRS PIGD Score | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS PIGD Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS PIGD Score ranges from -1 to 3, larger value shows worsening of conditions. |
| Adjusted Mean Change in H/Y Stage | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the H/Y Stage in the active treatment arm versus placebo between the baseline and 36 month visit. The change in H/Y Stage ranges from -1 to 3, larger value shows worsening of conditions. |
| Adjusted Mean Change in UPDRS Tremor Score | Baseline to 36 months of treatment | Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Tremor Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Tremor Score ranges from -1 to 2, larger value shows worsening of conditions. |
Countries
Canada, United States
Participant flow
Recruitment details
Patients were recruited from 57 Parkinson Study Group sites in North America from November 2014 through November 2015.
Pre-assignment details
413 patients were assessed for eligibility. 12 patients declined to participate and 65 patients were excluded (9 exclusionary medications, 2 other medical psychiatric or surgical, 5 disease too advanced, 6 diagnosis uncertain, 23 didn't meet other inclusion criteria, 20 other). 336 patients were enrolled and underwent randomization
Participants by arm
| Arm | Count |
|---|---|
| Isradipine Oral capsule of up to 5 mg of isradipine taken twice daily for 36 months.
Isradipine: Oral capsules Isradipine IR, up to 10 mg, taken twice daily | 170 |
| Placebo (for Isradipine) Oral capsule taken twice daily for 36 months.
Placebo (for Isradipine): Sugar Pill manufactured to look like Isradipine but has no active ingredients | 166 |
| Total | 336 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Isradipine | Total | Placebo (for Isradipine) |
|---|---|---|---|
| ADL Scale | 4.96 units on a scale STANDARD_DEVIATION 2.88 | 5.2 units on a scale STANDARD_DEVIATION 3.08 | 5.45 units on a scale STANDARD_DEVIATION 3.26 |
| Age, Continuous | 62.11 years STANDARD_DEVIATION 8.73 | 61.86 years STANDARD_DEVIATION 9.03 | 61.61 years STANDARD_DEVIATION 9.34 |
| BDI Total Score | 4.09 units on a scale STANDARD_DEVIATION 3.71 | 4.44 units on a scale STANDARD_DEVIATION 4.02 | 4.8 units on a scale STANDARD_DEVIATION 4.29 |
| Diastolic BP, Seated | 76.55 mmHg STANDARD_DEVIATION 9.72 | 77.18 mmHg STANDARD_DEVIATION 9.16 | 77.83 mmHg STANDARD_DEVIATION 8.52 |
| Disease Duration | 9.89 months STANDARD_DEVIATION 8.13 | 10.22 months STANDARD_DEVIATION 8.75 | 10.56 months STANDARD_DEVIATION 9.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 166 Participants | 326 Participants | 160 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Family History of PD | 30 Participants | 65 Participants | 35 Participants |
| Handedness Left | 20 Participants | 39 Participants | 19 Participants |
| Handedness Mixed | 3 Participants | 8 Participants | 5 Participants |
| Handedness Right | 147 Participants | 289 Participants | 142 Participants |
| H/Y Stage | 1.72 units on a scale STANDARD_DEVIATION 0.46 | 1.66 units on a scale STANDARD_DEVIATION 0.48 | 1.6 units on a scale STANDARD_DEVIATION 0.5 |
| Mental Scale | 0.61 units on a scale STANDARD_DEVIATION 0.87 | 0.71 units on a scale STANDARD_DEVIATION 1.05 | 0.81 units on a scale STANDARD_DEVIATION 1.21 |
| MoCA Score | 28.14 units on a scale STANDARD_DEVIATION 1.41 | 28.09 units on a scale STANDARD_DEVIATION 1.35 | 28.04 units on a scale STANDARD_DEVIATION 1.29 |
| Modified Rankin Score | 1.09 units on a scale STANDARD_DEVIATION 0.31 | 1.09 units on a scale STANDARD_DEVIATION 0.32 | 1.09 units on a scale STANDARD_DEVIATION 0.33 |
| Motor Scale | 18.08 units on a scale STANDARD_DEVIATION 7.3 | 17.21 units on a scale STANDARD_DEVIATION 6.97 | 16.32 units on a scale STANDARD_DEVIATION 6.53 |
| On Symptomatic Therapy (Amantadine) | 15 Participants | 26 Participants | 11 Participants |
| On Symptomatic Therapy (Anticholinergics) | 3 Participants | 5 Participants | 2 Participants |
| PDQ39 Total Score | 7.13 units on a scale STANDARD_DEVIATION 6.15 | 8.10 units on a scale STANDARD_DEVIATION 7.47 | 9.08 units on a scale STANDARD_DEVIATION 8.52 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 10 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 159 Participants | 308 Participants | 149 Participants |
| Region of Enrollment Canada | 16 participants | 33 participants | 17 participants |
| Region of Enrollment United States | 154 participants | 303 participants | 149 participants |
| SE/ADL | 94.44 units on a scale STANDARD_DEVIATION 5.23 | 94.24 units on a scale STANDARD_DEVIATION 6.05 | 94.04 units on a scale STANDARD_DEVIATION 6.8 |
| Sex: Female, Male Female | 48 Participants | 106 Participants | 58 Participants |
| Sex: Female, Male Male | 122 Participants | 230 Participants | 108 Participants |
| Systolic BP, Seated | 128.12 mmHg STANDARD_DEVIATION 17.17 | 127.91 mmHg STANDARD_DEVIATION 15.93 | 127.69 mmHg STANDARD_DEVIATION 14.6 |
| UPDRS Total Score | 23.66 units on a scale STANDARD_DEVIATION 8.64 | 23.13 units on a scale STANDARD_DEVIATION 8.59 | 22.58 units on a scale STANDARD_DEVIATION 8.53 |
| UPDRS Tremor Score | 0.51 units on a scale STANDARD_DEVIATION 0.32 | 0.51 units on a scale STANDARD_DEVIATION 0.3 | 0.50 units on a scale STANDARD_DEVIATION 0.29 |
| UPSDRS PIGD Score | 0.17 units on a scale STANDARD_DEVIATION 0.19 | 0.17 units on a scale STANDARD_DEVIATION 0.18 | 0.17 units on a scale STANDARD_DEVIATION 0.17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 170 | 1 / 166 |
| other Total, other adverse events | 163 / 170 | 154 / 166 |
| serious Total, serious adverse events | 26 / 170 | 27 / 166 |
Outcome results
Primary
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.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in Adjusted UPDRS Score | 13.49 score on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in Adjusted UPDRS Score | 13.85 score on a scale |
Primary
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.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in Total Unified Parkinson Disease Rating Scale (UPDRS) Score | 2.99 score on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in Total Unified Parkinson Disease Rating Scale (UPDRS) Score | 3.26 score on a scale |
Secondary
Adjusted Mean Change in Ambulatory Capacity
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Ambulatory Capacity in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Ambulatory Capacity ranges from -4 to 12, larger value shows worsening of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in Ambulatory Capacity | 0.59 score on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in Ambulatory Capacity | 0.50 score on a scale |
Secondary
Adjusted Mean Change in BDI Total Score
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the BDI Total Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in BDI Total Score ranges from -9 to 22, larger value shows worsening of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant in Placebo group had missing baseline UPDRS sections while had finished baseline BDI Score. And one participant in Isradipine group had missing BDI score at the visit of 36 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in BDI Total Score | 0.77 units on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in BDI Total Score | 1.34 units on a scale |
Secondary
Adjusted Mean Change in LED
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the LED(levodopa equivalent dose) in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED ranges from -100 to 3000, larger value shows more disability from PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline UPDRS sections while had finished baseline LED measurement. So LED had 1 more observation than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in LED | 389 mg |
| Placebo (for Isradipine) | Adjusted Mean Change in LED | 375 mg |
Secondary
Adjusted Mean Change in LED Cumulative
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the LED(levodopa equivalent dose) cumulative in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED cumulative ranges from 0 to 1200000, larger value shows more disability from PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline UPDRS sections while had finished baseline LED Cumulative measurement. So LED Cumulative had 1 more observation than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in LED Cumulative | 676 mg |
| Placebo (for Isradipine) | Adjusted Mean Change in LED Cumulative | 697 mg |
Secondary
Adjusted Mean Change in MDS-UPDRS mEDL
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS mEDL(Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MDS-UPDRS mEDL ranges from -8 to 35, larger value shows more disability from PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in MDS-UPDRS mEDL | 2.32 score on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in MDS-UPDRS mEDL | 2.57 score on a scale |
Secondary
Adjusted Mean Change in MDS-UPDRS nmEDL
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS nmEDL(Non-Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MDS-UPDRS nmEDL ranges from -6 to 10, larger value shows more disability from PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in MDS-UPDRS nmEDL | 1.93 score on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in MDS-UPDRS nmEDL | 1.76 score on a scale |
Secondary
Adjusted Mean Change in MoCA Score
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MoCA Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MoCA Score ranges from -10 to 6, larger value shows improvement of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline UPDRS sections while had finished baseline MoCA Score. So MoCA Score had 1 observation more than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in MoCA Score | -0.04 units on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in MoCA Score | -0.07 units on a scale |
Secondary
Adjusted Mean Change in Modified Rankin Score
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Modified Rankin Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Modified Rankin Score ranges from -1 to 3, larger value shows worsening of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline measurement for primary efficacy while had finished baseline Modified Rankin Score. So Modified Rankin Score had 1 more observation than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in Modified Rankin Score | 0.18 units on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in Modified Rankin Score | 0.29 units on a scale |
Secondary
Adjusted Mean Change in PDQ39 Total Score
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the PDQ39 Total Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in PDQ39 Total Score ranges from -16 to 44, larger value shows worsening of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. 7 patients had missing PDQ39 scores at the visit of 36 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in PDQ39 Total Score | 2.80 units on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in PDQ39 Total Score | 3.42 units on a scale |
Secondary
Adjusted Mean Change in SE/ADL
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the SE/ADL in the active treatment arm versus placebo between the baseline and 36 month visit. The change of UPDRS ranges from -70 to 20, larger value shows improvement of PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline UPDRS sections while had finished baseline SE/ADL measurement. So SE/ADL had 1 more observation than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in SE/ADL | -4.14 units on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in SE/ADL | -4.41 units on a scale |
Secondary
Adjusted Mean Change in UPDRS Part II
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part II (ADL Function) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part II ranges from -12 to 19, larger value shows more disability from PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in UPDRS Part II | 2.3 score on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in UPDRS Part II | 2.5 score on a scale |
Secondary
Adjusted Mean Change in UPDRS Part III OFF
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part III OFF rating in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part III OFF ranges from -30 to 100, larger value shows more disability from PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. 58 patients had missing measures at the visit of 36 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in UPDRS Part III OFF | 4.60 score on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in UPDRS Part III OFF | 4.50 score on a scale |
Secondary
Adjusted Mean Change in UPDRS Part IV
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part IV in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part IV ranges from -10 to 10, larger value shows more disability from PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. 46 patients had missing measures at the visit of 36 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in UPDRS Part IV | 1.18 score on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in UPDRS Part IV | 1.07 score on a scale |
Secondary
Adjusted Mean Change in UPDRS Score to 1 Year
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS nmEDL(Non-Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 12 month visit. The change of UPDRS ranges from -22 to 23, larger value shows more disability from PD.
Time frame: Baseline to 12 months of treatment
Population: Intention-to-treat (ITT) population. There were 169 patients in Isradipine group and 165 in placebo group who reached 1-year visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in UPDRS Score to 1 Year | 4.65 score on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in UPDRS Score to 1 Year | 5.3 score on a scale |
Secondary
Risk of Need for Antiparkinsonian Therapy
Number of participants with need for Antiparkinsonian Therapy.
Time frame: Baseline to 36 months of treatment
Population: Include all 336 patients that were randomized, no matter whether or not completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Isradipine | Risk of Need for Antiparkinsonian Therapy | 145 participants |
| Placebo (for Isradipine) | Risk of Need for Antiparkinsonian Therapy | 147 participants |
p-value: 0.07395% CI: [0.61, 1.03]Log Rank
Secondary
Risk of Need for Dyskinesia
Number of participants with need for Dyskinesia Therapy.
Time frame: Baseline to 36 months of treatment
Population: Include all 336 patients that were randomized, no matter whether or not completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Isradipine | Risk of Need for Dyskinesia | 24 participants |
| Placebo (for Isradipine) | Risk of Need for Dyskinesia | 19 participants |
p-value: 0.2195% CI: [0.78, 3.01]Log Rank
Secondary
Risk of Need for Fluctuations
Number of participants with need for Fluctuations Therapy.
Time frame: Baseline to 36 months of treatment
Population: Include all 336 patients that were randomized, no matter whether or not completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Isradipine | Risk of Need for Fluctuations | 57 participants |
| Placebo (for Isradipine) | Risk of Need for Fluctuations | 64 participants |
p-value: 0.3595% CI: [0.56, 1.22]Log Rank
Other Pre-specified
Adjusted Mean Change in Diastolic BP, Seated
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Diastolic BP, Seated in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Diastolic BP, Seated ranges from -35 to 25. larger value shows worsening of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline UPDRS sections while had finished baseline Diastolic BP, Seated. So Diastolic BP had 1 observation more than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in Diastolic BP, Seated | -4.64 mmHg |
| Placebo (for Isradipine) | Adjusted Mean Change in Diastolic BP, Seated | -0.71 mmHg |
Other Pre-specified
Adjusted Mean Change in H/Y Stage
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the H/Y Stage in the active treatment arm versus placebo between the baseline and 36 month visit. The change in H/Y Stage ranges from -1 to 3, larger value shows worsening of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline UPDRS sections while had finished baseline H/Y Stage. So H/Y Stage had 1 observation more than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in H/Y Stage | 0.15 units on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in H/Y Stage | 0.21 units on a scale |
Other Pre-specified
Adjusted Mean Change in Levodopa
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Levodopa in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED ranges from -200 to 2000, larger value shows more disability from PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline UPDRS sections while had finished baseline Levodopa. So Levodopa had 1 observation more than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in Levodopa | 307 mg |
| Placebo (for Isradipine) | Adjusted Mean Change in Levodopa | 307 mg |
Other Pre-specified
Adjusted Mean Change in Levodopa Cumulative
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Levodopa Cumulative in the active treatment arm versus placebo between the baseline and 36 month visit. The change of Levodopa cumulative ranges from 0 to 800000, larger value shows more disability from PD.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline UPDRS sections while had finished baseline Levodopa Cumulative. So Levodopa Cumulative had 1 observation more than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in Levodopa Cumulative | 471 mg |
| Placebo (for Isradipine) | Adjusted Mean Change in Levodopa Cumulative | 508 mg |
Other Pre-specified
Adjusted Mean Change in Systolic BP, Seated
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Systolic BP, Seated in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Systolic BP, Seated ranges from -65 to 50. larger value shows worsening of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population. One participant had missing baseline UPDRS sections while had finished baseline Systolic BP, Seated. So Systolic BP had 1 observation more than primary outcomes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in Systolic BP, Seated | -6.11 mmHg |
| Placebo (for Isradipine) | Adjusted Mean Change in Systolic BP, Seated | 1.03 mmHg |
Other Pre-specified
Adjusted Mean Change in UPDRS PIGD Score
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS PIGD Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS PIGD Score ranges from -1 to 3, larger value shows worsening of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in UPDRS PIGD Score | 0.12 units on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in UPDRS PIGD Score | 0.10 units on a scale |
Other Pre-specified
Adjusted Mean Change in UPDRS Tremor Score
Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Tremor Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Tremor Score ranges from -1 to 2, larger value shows worsening of conditions.
Time frame: Baseline to 36 months of treatment
Population: Intention-to-treat (ITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Isradipine | Adjusted Mean Change in UPDRS Tremor Score | 0.00 units on a scale |
| Placebo (for Isradipine) | Adjusted Mean Change in UPDRS Tremor Score | 0.01 units on a scale |