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Pioglitazone in Alzheimer Disease

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ClinicalTrials.gov Identifier: NCT00982202
Recruitment Status : Completed
First Posted : September 23, 2009
Last Update Posted : September 23, 2009
Takeda Pharmaceuticals North America, Inc.
Information provided by:
National Institute on Aging (NIA)

Brief Summary:
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 or disease Intervention/treatment Phase
Alzheimer Disease Drug: pioglitazone Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pioglitazone in Alzheimer Disease Progression
Study Start Date : January 2002
Actual Primary Completion Date : January 2005
Actual Study Completion Date : January 2005

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Frequency of adverse events [ Time Frame: baseline, monthly for 1 year, then 15 and 18 months ]

Secondary Outcome Measures :
  1. Laboratory abnormalities [ Time Frame: baseline, monthly for 1 year, then 15 and 18 months ]
  2. Cognition [ Time Frame: baseline, 3, 6, 9, 12, 15, and 18 months ]
  3. Activities of Daily Living (ADL) [ Time Frame: baseline, 3, 6, 9, 12, 15, and 18 months ]
  4. Behavior [ Time Frame: baseline, 3, 6, 9, 12, 15, and 18 months ]
  5. Global function [ Time Frame: baseline, 3, 6, 9, 12, 15, and 18 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00982202

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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
National Institute on Aging (NIA)
Takeda Pharmaceuticals North America, Inc.
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Principal Investigator: David Geldmaher, MD University of Virginia Health System
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: David Geldmaher, MD, University of Virginia Health System
ClinicalTrials.gov Identifier: NCT00982202    
Other Study ID Numbers: IA0168
1R01AG018905 ( U.S. NIH Grant/Contract )
First Posted: September 23, 2009    Key Record Dates
Last Update Posted: September 23, 2009
Last Verified: September 2009
Keywords provided by National Institute on Aging (NIA):
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Hypoglycemic Agents
Physiological Effects of Drugs