Pioglitazone in Early Parkinson's Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
University of Rochester
ClinicalTrials.gov Identifier:
NCT01280123
First received: December 3, 2010
Last updated: October 22, 2013
Last verified: September 2013
  Purpose

This is a multi-center, double-blind, placebo controlled clinical trial of two dosages of oral pioglitazone (15 milligram(mg) and 45 milligram (mg)) for safety, tolerability, and futility.

Subjects who are on stable dose of rasagiline 1 mg/day or selegiline 10 mg/day for at least 8 weeks but no more than 8 months, will be randomized to one of two dosages of oral pioglitazone (15 mg and 45 mg) or matching placebo.

The study will measure disease progression by the change in total UPDRS score between the baseline visit and 44 weeks.


Condition Intervention Phase
Parkinson's Disease
Drug: Pioglitazone
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-Center, Double-Blind, Placebo-Controlled Phase II Study of Pioglitazone in Early Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Change in total Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to 44 weeks [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    Change in total UPDRS score from baseline to 44 weeks (in subjects treated with rasagiline 1 mg/day or selegiline 10 mg/day


Secondary Outcome Measures:
  • Change in Individual Parts I - IV of the Unified Parkinson's Disease Rating Scale (UPDRS) from baseline to 44 weeks [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    Compare the scores of the individual parts of the UPDRS. Part 1 assesses mentation, behavior and mood. Part II assesses activities of daily living in the week prior to the designated visit. Part III assesses the motor abilities at the time of the visit. Part IV assesses complications of therapy, for example (e.g.) dyskinesia, fluctuation, sleep disturbances, symptomatic orthostasis.

  • Change in Ambulatory Capacity from Baseline to 44 weeks [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    This is the sum of the 5 UPDRS questions regarding ambulatory capacity: falling, freezing, walking, gait, postural stability.

  • Change in Schwab and England scale from baseline to 44 weeks [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    The Schwab & England scale is an investigator and subject assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he'she did before Parkinson's disease appeared.

  • Change in Parkinson's Disease Questionnaire (PDQ-39) from baseline to 44 weeks [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    The Parkinson's Disease Questionnaire (PDQ-39) is a short, 39 item measure of quality of life in subjects with Parkinson's disease. The questionnaire covers 8 aspects of quality of life: mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication and bodily discomfort.

  • Change in the Mattis Dementia Rating Scale (DRS-2)from baseline to 44 weeks [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    The Mattis dementia rating scale is a psychometric instrument designed to assess the extent and nature of dementia. The scale consists of content that covers: attention, initiation/perseveration, construction, conceptualization, and memory.

  • Change in the 15-item Geriatric Depression Scale (GDS-15)from baseline to 44 weeks [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    The Geriatric Depression Scale - 15 is a short 15 yes or no question instrument for assessing depression in the elderly. It has been found to be particularly useful in assessing depression in Parkinson's Disease.

  • Number of subject who complete the study on their assigned dose of study drug. [ Time Frame: 44 weeks ] [ Designated as safety issue: Yes ]
    To assess safety and tolerability we will analyze the number of subjects who complete the study on their assigned dose of study drug, compared to subjects who had a dose reduction, or dose suspension.

  • Number of Subjects with Adverse Events [ Time Frame: 44 weeks ] [ Designated as safety issue: Yes ]
    To assess safety and tolerability we will monitor and analyze adverse event frequency and severity, changes in vital signs or clinical laboratory values.

  • University of Pennsylvania Smell Identification Test (UPSIT) at Baseline [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    The UPSIT, an odor identification test, will be used as an exploratory biomarker in this trial to determine if it is sensitive and specific for the clinical diagnosis of PD at the end of trial.

  • Potential Biomarkers of response to pioglitazone in blood and urine from Baseline to 44 weeks. [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
    Exploratory potential peripheral (blood and urine) biomarkers of response to pioglitazone will be measured in this trial at baseline, week 16 and week 44. The selected biomarkers are relevant to pathogenesis of Parkinson's disease (mitochondrial dysfunction, oxidative stress, and inflammation) and the hypothesized mechanism of potential neuroprotection by pioglitazone.


Estimated Enrollment: 216
Study Start Date: March 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 15 mg pioglitazone
15 mg pioglitazone
Drug: Pioglitazone

Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: Subjects who are on stable dose of rasagiline 1 mg/day or selegiline 10 mg/day, for at least 8 weeks but no more than 8 months, will begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Other Names:
  • Pioglitazone Hydrochloride
  • ACTOS (R)
Experimental: 45 mg pioglitazone
45 mg pioglitazone
Drug: Pioglitazone

Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd or matching placebo

44 weeks: Subjects who are on stable dose of rasagiline 1 mg/day or selegiline 10 mg/day, for at least 8 weeks but no more than 8 months, will begin randomized dose of study drug. Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated. Subjects will be followed on study drug for 44 weeks.

Other Names:
  • Pioglitazone Hydrochloride
  • ACTOS (R)
Placebo Comparator: Matching Placebo
Placebo
Drug: placebo
Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to give informed consent.
  2. Men and women with idiopathic PD of less than 5 years duration from diagnosis with a Hoehn and Yahr Stage < 2.
  3. On stable dosage of rasagiline 1 mg/day or selegiline 10 mg/day for at least 8 weeks but not more than 8 months prior to baseline. Expected to remain on stable dose of rasagiline or selegiline as the only treatment for their PD for the duration of the study (44 weeks).
  4. Diagnosis must be confirmed by bradykinesia plus one of the other cardinal signs (resting tremor, rigidity) being present, without any other known or suspected cause of parkinsonism. The clinical signs must be asymmetric.
  5. Subjects may be taking stable doses (30 days) of anticholinergics or creatine (< 5gm/day) but must be expected to remain on the same dose.
  6. Age > 30 years.
  7. Women who are not postmenopausal or surgically sterile must use a medically accepted contraceptive regimen for at least 60 days before the baseline visit, and agree to continue such use throughout the duration of the study and for 30 days after the final dose of study drug. Reliable forms of contraception include intrauterine devices in place for at least 3 months, surgical infertility, abstinence, or adequate barrier methods in conjunction with spermicide. Women must have a pregnancy test unless they are at least 2 years postmenopausal or surgically sterile. Women of childbearing potential must have a negative pregnancy test at baseline and be non-lactating.

Exclusion Criteria:

  1. Exposure to dopaminergic PD therapy or amantadine within 60 days prior to baseline visit or for 90 days or more at any point in the past (See Protocol Section 7.3, table 1)
  2. Use of any of the following drugs within 180 days prior to baseline: neuroleptics, metoclopramide, alpha-methyldopa, clozapine, olanzapine and flunarizine.
  3. Use of any of the following drugs within 90 days prior to baseline: methylphenidate, cinnarizine, reserpine, tetrabenazine, amphetamine or MAO-A inhibitors (pargyline, phenelzine, and tranylcypromine).
  4. Presence of drug-induced parkinsonism (e.g., metoclopramide, flunarizine), metabolic identified neurogenetic disorders (e.g., Wilson's disease), encephalitis, or other atypical Parkinsonian syndromes (e.g., progressive supranuclear palsy, multiple system atrophy).
  5. Participation in other drug studies or receipt of other investigational drugs within 30 days prior to baseline or during the study.
  6. Presence of freezing.
  7. Any clinically significant psychiatric or medical condition (e.g., active GI illnesses, angina, active neoplasm) or laboratory abnormality, which would in the judgment of the Investigator interfere with the subject's ability to participate in the study or to be followed.
  8. History of stereotaxic brain surgery for PD (e.g., pallidotomy, deep brain stimulation, fetal tissue transplant).
  9. Clinically significant structural brain disease that the investigator believes would interfere with study evaluations.
  10. History of congestive heart failure.
  11. Use of pioglitazone or rosiglitazone within 90 days before randomization.
  12. Known intolerance to pioglitazone or rosiglitazone.
  13. Allergy to rasagiline or selegiline, or contraindication to rasagiline or selegiline use.
  14. Type I or Type II diabetes mellitus.
  15. HgbA1C greater than or equal to 6% at Screening.
  16. Known liver disease or elevation of AST or ALT greater than 2.5 times the upper limit of normal.
  17. Known history of osteoporosis. All women ≥ 65 years of age or men and woman at high risk of osteoporosis should have documented evidence of screening for osteoporosis. Factors associated with high risk of osteoporosis include: previous non traumatic fracture, chronic glucocorticoid use, body weight under 58 kg, family history of hip fracture, current cigarette smoking, and excessive alcohol intake.
  18. Drug or alcohol use or dependence that, in the opinion of the Investigator, would interfere with the safe conduct of the study.
  19. Significant peripheral edema (2+ or more) of the extremities of any etiology.
  20. Current or planned use of gemfibrozil or rifampin during the trial.
  21. History of bladder cancer.
  22. Evidence of hematuria which has not been evaluated for evidence of bladder cancer. (Documentation of work up or a repeat urine test that was negative for hematuria and the PCP or urologist does not feel that further work up is required.)
  23. History of macular edema.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01280123

  Hide Study Locations
Locations
United States, Alabama
Univeristy of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-0017
United States, Arizona
Barrow Neurological Institute
Phoenix, Arizona, United States, 85013
United States, California
The Parkinson's & Movement Disorder Institute
Fountain Valley, California, United States, 92708
University of Southern California
Los Angeles, California, United States, 90083
University of California San Fransisco
San Fransisco, California, United States, 94143-0114
United States, Colorado
Univeristy of Colorado Denver
Aurora, Colorado, United States, 80045
United States, Florida
University of Florida
Gainsville, Florida, United States, 32610
University of Florida, Jacksonville
Jacksonville, Florida, United States, 32209
University of Miami
Miami, Florida, United States, 33136
University of South Florida
Tampa, Florida, United States, 33606
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30329
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Hawaii
Pacific Health Research & Education Institute
Honolulu, Hawaii, United States, 96819
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
LSU Health Science Center Shreveport
Shreveport, Louisiana, United States, 71103
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-0875
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-5316
Michigan State University
East Lansing, Michigan, United States, 48824
United States, Minnesota
Struthers Parkinson's Center
Golden Valley, Minnesota, United States, 55427
United States, Missouri
Washington University
St Louis, Missouri, United States, 63110
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
SUNY Downstate Medical Center
Brooklyn, New York, United States, 11203-2098
North Shore - LIJ Health System
Manhasset, New York, United States, 11030
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29401
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390-9036
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05405
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22903
Sponsors and Collaborators
University of Rochester
Michael J. Fox Foundation for Parkinson's Research
Investigators
Study Director: Tanya Simuni, MD Northwestern University
Study Director: Karl Kieburtz, MD MPH University of Rochester
  More Information

No publications provided

Responsible Party: University of Rochester
ClinicalTrials.gov Identifier: NCT01280123     History of Changes
Other Study ID Numbers: FS-ZONE
Study First Received: December 3, 2010
Last Updated: October 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Rochester:
Parkinson's Disease
Biomarkers

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014