Pioglitazone in Early Parkinson's Disease

NCT01280123 | Completed Phase 2 Results DMC

• 2 other identifiers: FS-ZONE5U01NS043128-12
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 38

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score From Baseline to 44 Weeks

  Change in total UPDRS score from baseline to 44 weeks (in subjects treated with rasagiline 1 mg/day or selegiline 10 mg/day). The Total UPDRS is the sum of parts I, II, and III. The possible range of the total UPDRS is from 0-176. Higher values indicate worse outcomes. The change is 44 weeks - baseline.

  44 weeks

Secondary Outcomes (5)

• Change in Ambulatory Capacity From Baseline to 44 Weeks

  44 weeks

• Change in Schwab and England Scale From Baseline to 44 Weeks

  44 weeks

• Change in Parkinson's Disease Questionnaire (PDQ-39) From Baseline to 44 Weeks

  44 weeks

• Change in the Mattis Dementia Rating Scale (DRS-2)From Baseline to 44 Weeks

  44 weeks

• Change in the 15-item Geriatric Depression Scale (GDS-15)From Baseline to 44 Weeks

  44 weeks

Study Arms (3)

15 mg pioglitazone

EXPERIMENTAL

15 mg pioglitazone

Drug: Pioglitazone

45 mg pioglitazone

EXPERIMENTAL

45 mg pioglitazone

Drug: Pioglitazone

Matching Placebo

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

Pioglitazone 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.

Also known as: Pioglitazone Hydrochloride, ACTOS (R)

15 mg pioglitazone; 45 mg pioglitazone

placebo 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.

Matching Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give informed consent.
• Men and women with idiopathic PD of less than 5 years duration from diagnosis with a Hoehn and Yahr Stage \< 2.
• 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).
• 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.
• Subjects may be taking stable doses (30 days) of anticholinergics or creatine (\< 5gm/day) but must be expected to remain on the same dose.
• Age \> 30 years.
• 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.

You may not qualify if:

• 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
• Use of any of the following drugs within 180 days prior to baseline: neuroleptics, metoclopramide, alpha-methyldopa, clozapine, olanzapine and flunarizine.
• 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).
• 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).
• Participation in other drug studies or receipt of other investigational drugs within 30 days prior to baseline or during the study.
• Presence of freezing.
• 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.
• History of stereotaxic brain surgery for PD
• Clinically significant structural brain disease that the investigator believes would interfere with study evaluations.
• History of congestive heart failure.
• Use of pioglitazone or rosiglitazone within 90 days before randomization.
• Known intolerance to pioglitazone or rosiglitazone.
• Allergy to rasagiline or selegiline, or contraindication to rasagiline or selegiline use.
• Type I or Type II diabetes mellitus.
• HgbA1C greater than or equal to 6% at Screening.

Sponsors & Collaborators

• University of Rochester: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (38)

Univeristy of Alabama at Birmingham

Birmingham, Alabama, 35294-0017, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

The Parkinson's & Movement Disorder Institute

Fountain Valley, California, 92708, United States

Location

University of Southern California

Los Angeles, California, 90083, United States

Location

University of California San Fransisco

San Francisco, California, 94143-0114, United States

Location

Univeristy of Colorado Denver

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainsville, Florida, 32610, United States

Location

University of Florida, Jacksonville

Jacksonville, Florida, 32209, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

Pacific Health Research & Education Institute

Honolulu, Hawaii, 96819, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

LSU Health Science Center Shreveport

Shreveport, Louisiana, 71103, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287-0875, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5316, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Struthers Parkinson's Center

Golden Valley, Minnesota, 55427, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203-2098, United States

Location

North Shore - LIJ Health System

Manhasset, New York, 11030, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29401, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9036, United States

Location

University of Vermont

Burlington, Vermont, 05405, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Related Publications (2)

• 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.

  PMID: 26116315 RESULT

• 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.

  PMID: 25227476 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Tanya Simuni, MD
• Organization: Northwestern University

TSimuni@nm.org

Study Officials

• Tanya Simuni, MD

  Northwestern University

  STUDY DIRECTOR

• Karl Kieburtz, MD MPH

  University of Rochester

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2010
• First Posted: January 20, 2011
• Study Start: March 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: October 14, 2015
• Results First Posted: October 14, 2015

Record last verified: 2013-09

Locations

US (38)