Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
Trial record 1 of 13 for:    Steady PD III
Previous Study | Return to List | Next Study

Efficacy of Isradipine in Early Parkinson Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02168842
Recruitment Status : Completed
First Posted : June 20, 2014
Results First Posted : January 14, 2020
Last Update Posted : January 14, 2020
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Michael J. Fox Foundation for Parkinson's Research
The Parkinson Study Group
Information provided by (Responsible Party):
Robert Holloway, University of Rochester

Tracking Information
First Submitted Date  ICMJE June 18, 2014
First Posted Date  ICMJE June 20, 2014
Results First Submitted Date  ICMJE December 6, 2019
Results First Posted Date  ICMJE January 14, 2020
Last Update Posted Date January 14, 2020
Actual Study Start Date  ICMJE November 2014
Actual Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2020)
  • Adjusted Mean Change in Total Unified Parkinson Disease Rating Scale (UPDRS) Score [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 18, 2014)
Unified Parkinson Disease Rating Scale (UPDRS) [ Time Frame: Baseline to 36 month visit ]
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.
Change History Complete list of historical versions of study NCT02168842 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2020)
  • Adjusted Mean Change in LED [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 II [ Time Frame: 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 UPDRS Part III OFF [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • Adjusted Mean Change in MoCA Score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline to 36 months of treatment ]
    Number of participants with need for Antiparkinsonian Therapy.
  • Risk of Need for Dyskinesia [ Time Frame: Baseline to 36 months of treatment ]
    Number of participants with need for Dyskinesia Therapy.
  • Risk of Need for Fluctuations [ Time Frame: Baseline to 36 months of treatment ]
    Number of participants with need for Fluctuations Therapy.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2014)
  • Motor function [ Time Frame: Baseline to 36 months of treatment ]
    To explore long term efficacy of isradipine treatment to slow progression of disability as measured by motor function (characterized by UPDRS Part III in the medications OFF state, UPDRS ambulatory capacity subscore, time to initiation of symptomatic therapy, time to onset of motor complications, dosage and utilization of symptomatic therapy, MDS-UPDRS Motor score)
  • Cognitive function [ Time Frame: Baseline to 36 months of treatment ]
    To explore long term efficacy of isradipine treatment to slow progression of disability as measured by cognitive function as measured by the Montreal Cognitive assessment Scale (MoCA)
  • Global measures [ Time Frame: Baseline to 36 months of treatment ]
    To explore long term efficacy of isradipine treatment to slow progression of disability as measured by Global measures of disability as measured by modified Rankin score
  • Functional status and quality of life [ Time Frame: Baseline to 36 months of treatment ]
    To explore long-term efficacy of isradipine to slow progression of disability as measured by functional status and quality of life (PDQ-39, MDS- UPDRS Motor and Non-Motor Experience of Daily Living)
Current Other Pre-specified Outcome Measures
 (submitted: January 7, 2020)
  • Adjusted Mean Change in UPDRS PIGD Score [ Time Frame: 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 UPDRS Tremor Score [ Time Frame: 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.
  • Adjusted Mean Change in H/Y Stage [ Time Frame: 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 Levodopa [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Isradipine in Early Parkinson Disease
Official Title  ICMJE 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Parkinson Disease
Intervention  ICMJE
  • Drug: Isradipine
    Oral capsules Isradipine IR, up to 10 mg, taken twice daily
  • Drug: Placebo (for Isradipine)
    Sugar Pill manufactured to look like Isradipine but has no active ingredients
Study Arms  ICMJE
  • Active Comparator: Isradipine
    Oral capsule of up to 5 mg of isradipine taken twice daily for 36 months.
    Intervention: Drug: Isradipine
  • Placebo Comparator: Placebo (for Isradipine)
    Oral capsule taken twice daily for 36 months.
    Intervention: Drug: Placebo (for Isradipine)
Publications * McFarthing K, Simuni T. Clinical Trial Highlights: Phase III Study in Spotlight. J Parkinsons Dis. 2019;9(1):3-4. doi: 10.3233/JPD-190002.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 18, 2014)
336
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2018
Actual Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02168842
Other Study ID Numbers  ICMJE STEADY-PD III
U01NS080818-01A1 ( U.S. NIH Grant/Contract )
U01NS080840-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Robert Holloway, University of Rochester
Study Sponsor  ICMJE University of Rochester
Collaborators  ICMJE
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Michael J. Fox Foundation for Parkinson's Research
  • The Parkinson Study Group
Investigators  ICMJE
Principal Investigator: Tanya Simuni, MD Northwestern University
Principal Investigator: Robert Holloway, MD MPH University of Rochester
PRS Account University of Rochester
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP