Pioglitazone in Early Parkinson's Disease

NCT ID: NCT01280123

Last Updated: 2015-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2014-05-31

Brief Summary

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 Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline visit and 44 weeks.

Detailed Description

A Multi-Center, Double-Blind, Placebo-Controlled Phase II Study of Pioglitazone in Early Parkinson's Disease (PD). The patient population has early stage PD (< 5 years from diagnosis), must be treated with 1 mg/day of rasagiline or 10 mg/day of selegiline for at least 8 weeks but not more than 8 months prior to enrollment.

The primary objective of this clinical trial is to assess the futility of pioglitazone on PD disease progression as measured by the change in total UPDRS score between the baseline visit and 44 weeks. The secondary objectives of the study are to collect additional efficacy and safety/tolerability data to be used in planning a subsequent Phase III trial of pioglitazone in early, treated PD. Measures of cognition, mood and blood- and urine-based biomarkers will also be explored. Subjects in this trial are randomly assigned in a 1:1:1 ratio to one of three study arms: 15 mg, 45 mg or placebo.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

15 mg pioglitazone

15 mg pioglitazone

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

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

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.

45 mg pioglitazone

45 mg pioglitazone

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

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

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.

Matching Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

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.

Interventions

Pioglitazone

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

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Pioglitazone Hydrochloride; ACTOS (R)

Eligibility 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.

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

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 monoamine oxidase (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 or laboratory abnormality, which would in the judgment of the Investigator interfere with the subject's ability to participate.

8. History of stereotaxic brain surgery for PD

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 primary care physician or urologist does not feel that further work up is required.)

23. History of macular edema.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tanya Simuni, MD

Role: STUDY_DIRECTOR

Northwestern University

Karl Kieburtz, MD MPH

Role: STUDY_DIRECTOR

University of Rochester

Locations

Univeristy of Alabama at Birmingham

Birmingham, Alabama, United States

Barrow Neurological Institute

Phoenix, Arizona, United States

The Parkinson's & Movement Disorder Institute

Fountain Valley, California, United States

University of Southern California

Los Angeles, California, United States

University of California San Fransisco

San Francisco, California, United States

Univeristy of Colorado Denver

Aurora, Colorado, United States

University of Florida

Gainsville, Florida, United States

University of Florida, Jacksonville

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Medical College of Georgia

Augusta, Georgia, United States

Pacific Health Research & Education Institute

Honolulu, Hawaii, United States

Northwestern University

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Kentucky

Lexington, Kentucky, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

LSU Health Science Center Shreveport

Shreveport, Louisiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Michigan State University

East Lansing, Michigan, United States

Struthers Parkinson's Center

Golden Valley, Minnesota, United States

Washington University

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

SUNY Downstate Medical Center

Brooklyn, New York, United States

North Shore - LIJ Health System

Manhasset, New York, United States

Duke University

Durham, North Carolina, United States

Oregon Health & Science University

Portland, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

University of Vermont

Burlington, Vermont, United States

University of Virginia

Charlottesville, Virginia, United States

Countries

United States

References

NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators. Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial. Lancet Neurol. 2015 Aug;14(8):795-803. doi: 10.1016/S1474-4422(15)00144-1. Epub 2015 Jun 23.

Reference Type: RESULT

PMID: 26116315 (View on PubMed)

Carta AR, Simuni T. Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson's disease. Expert Opin Investig Drugs. 2015 Feb;24(2):219-27. doi: 10.1517/13543784.2015.963195. Epub 2014 Sep 17.

Reference Type: DERIVED

PMID: 25227476 (View on PubMed)

Other Identifiers

5U01NS043128-12

Identifier Type: NIH

Identifier Source: secondary_id

View Link

FS-ZONE

Identifier Type: -

Identifier Source: org_study_id