Pioglitazone in Alzheimer Disease

This study has been completed.
Sponsor:
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by:
National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:
NCT00982202
First received: September 22, 2009
Last updated: NA
Last verified: September 2009
History: No changes posted
  Purpose

This study was designed to assess the safety and tolerability of pioglitazone, an approved drug for type 2 diabetes, in non diabetic patients with Alzheimer's disease. It was also designed to generate preliminary information on whether pioglitazone might slow progression of Alzheimer's disease.


Condition Intervention Phase
Alzheimer Disease
Drug: pioglitazone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pioglitazone in Alzheimer Disease Progression

Resource links provided by NLM:


Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:
  • Frequency of adverse events [ Time Frame: baseline, monthly for 1 year, then 15 and 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Laboratory abnormalities [ Time Frame: baseline, monthly for 1 year, then 15 and 18 months ] [ Designated as safety issue: Yes ]
  • Cognition [ Time Frame: baseline, 3, 6, 9, 12, 15, and 18 months ] [ Designated as safety issue: No ]
  • Activities of Daily Living (ADL) [ Time Frame: baseline, 3, 6, 9, 12, 15, and 18 months ] [ Designated as safety issue: No ]
  • Behavior [ Time Frame: baseline, 3, 6, 9, 12, 15, and 18 months ] [ Designated as safety issue: No ]
  • Global function [ Time Frame: baseline, 3, 6, 9, 12, 15, and 18 months ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: January 2002
Study Completion Date: January 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PGZ Drug: pioglitazone
15mg tablet daily, increase by one pill at one-week intervals based on reported tolerability; maintain best tolerated dose (1 to 3 tablets daily) for ~18months
Other Name: Actos
Placebo Comparator: Placebo Drug: Placebo
1 to 3 tablets daily for ~18 months

Detailed Description:

Inflammatory processes are important in the progressive loss of memory and thinking skills in Alzheimer's disease (AD). Laboratory studies show that drugs that bind to a protein known as "Peroxisome Proliferator Activated Receptor-gamma (PPARgamma)" act to reduce inflammatory responses in brain cells known as microglia when they are exposed to amyloid peptide, a major part of AD pathology. Therefore, drugs that activate PPARgamma have great potential for reducing the progression of AD. Pioglitazone (PGZ) activates PPARgamma and has shown favorable clinical experiences and safety profiles in patients with diabetes. This is a pilot study to determine the safety and tolerability of PGZ in patients with AD. Another goal of the study is to assess how clinical measures of cognition, daily function, and behavior might respond to PGZ treatment.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • CT or MRI since disease onset excluding structural lesions sufficient to account for the participant's dementia
  • Mini-Mental State Exam (MMSE) score between 12 and 26, inclusively
  • Clinical Dementia Rating (CDR) score of 1 or 2 (mild to moderate AD severity) at both screening and baseline
  • Women must be 2-years post-menopausal or surgically sterile.
  • Generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane); vision and hearing (hearing aid permissible) sufficient for compliance with testing procedures
  • Concomitant medications: Participants may be on stable doses of cholinesterase inhibitors for 90 days prior to screening (may not be started during the trial); antidepressant or antipsychotic medications are acceptable if symptoms are controlled and therapy is at stable dosage for at least 30 days prior to screening; vitamin E at 200 IU daily will be provided to all participants beginning at baseline/randomization (higher doses must be discontinued at the screening visit)

Exclusion Criteria:

  • Absence of a reliable caregiver who is willing to participate and comply with protocol responsibilities
  • Diabetes mellitus requiring medical therapy (diet-controlled diabetes is acceptable)
  • Acute or chronic liver failure, hepatitis within the last two years, or history of drug-induced liver transaminase elevations
  • Heart failure meeting New York Heart Association Grade III or IV criteria (i.e., functionally disabling)
  • Evidence of active gastrointestinal, renal, pulmonary, endocrine or cardiovascular system disease sufficient to cause cognitive impairment or interfere with past levels of daily function; participants with controlled hypertension (supine diastolic BP < 95mmHg), right bundle branch block (complete or partial) and pacemakers may be included in the study; participants with thyroid disease also may be included in the study, provided they are euthyroid on treatment
  • Active treatment for cancer or history of cancer within 3 years of screening (basal cell and squamous cells skin cancers are acceptable; incidental finding of carcinoma cells at transurethral prostate resection without subsequent medical or surgical therapy is acceptable)
  • Evidence of other psychiatric/neurologic disorders sufficient to be the primary source of cognitive impairment (i.e., stroke, idiopathic Parkinson's disease, schizophrenia, bipolar or unipolar depression, seizure disorder, head injury with loss of consciousness within the past year) or a modified Hachinski's ischemia score of 5 or greater; delusions, hallucinations or depression not successfully treated or not on stable medical therapy for these conditions 30 days prior to enrollment; known or suspected history (within the past 10 years) of alcoholism or drug misuse
  • Participants and/or caregivers who are unwilling or unable to fulfill the requirements of the study
  • Any condition which would make the participant or the caregiver, in the opinion of the investigator, unsuitable for the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00982202

Locations
United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44120
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Takeda Pharmaceuticals North America, Inc.
Investigators
Principal Investigator: David Geldmaher, MD University of Virginia Health System
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David Geldmaher, MD, University of Virginia Health System
ClinicalTrials.gov Identifier: NCT00982202     History of Changes
Other Study ID Numbers: IA0168, 1R01AG018905
Study First Received: September 22, 2009
Last Updated: September 22, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institute on Aging (NIA):
PPAR-gamma
inflammation

Additional relevant MeSH terms:
Alzheimer Disease
Disease Progression
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Disease Attributes
Pathologic Processes
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014