Pioglitazone in Alzheimer Disease

NCT00982202 | Completed Phase 2 DMC

• 2 other identifiers: IA01681R01AG018905
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Alzheimer Disease

Keywords

PPAR-gamma; inflammation

Outcome Measures

Primary Outcomes (1)

• Frequency of adverse events

  baseline, monthly for 1 year, then 15 and 18 months

Secondary Outcomes (5)

• Laboratory abnormalities

  baseline, monthly for 1 year, then 15 and 18 months

• Cognition

  baseline, 3, 6, 9, 12, 15, and 18 months

• Activities of Daily Living (ADL)

  baseline, 3, 6, 9, 12, 15, and 18 months

• Behavior

  baseline, 3, 6, 9, 12, 15, and 18 months

• Global function

  baseline, 3, 6, 9, 12, 15, and 18 months

Study Arms (2)

PGZ

EXPERIMENTAL

Drug: pioglitazone

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

pioglitazone DRUG

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

Also known as: Actos

PGZ

Placebo DRUG

1 to 3 tablets daily for \~18 months

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute on Aging (NIA): lead
• Takeda Pharmaceuticals North America, Inc.: collaborator

Study Sites (2)

University Hospitals of Cleveland

Cleveland, Ohio, 44120, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (4)

• Heneka MT, Sastre M, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, O'Banion K, Klockgether T, Van Leuven F, Landreth GE. Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain. 2005 Jun;128(Pt 6):1442-53. doi: 10.1093/brain/awh452. Epub 2005 Apr 7.

  PMID: 15817521 BACKGROUND

• Jiang Q, Heneka M, Landreth GE. The role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in Alzheimer's disease: therapeutic implications. CNS Drugs. 2008;22(1):1-14. doi: 10.2165/00023210-200822010-00001.

  PMID: 18072811 BACKGROUND

• Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007 Sep 12;298(10):1180-8. doi: 10.1001/jama.298.10.1180.

  PMID: 17848652 BACKGROUND

• Geldmacher DS, Fritsch T, McClendon MJ, Landreth G. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Arch Neurol. 2011 Jan;68(1):45-50. doi: 10.1001/archneurol.2010.229. Epub 2010 Sep 13.

  PMID: 20837824 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Inflammation

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• David Geldmaher, MD

  University of Virginia Health System

  PRINCIPAL INVESTIGATOR

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: NIH

Study Record Dates

• First Submitted: September 22, 2009
• First Posted: September 23, 2009
• Study Start: January 1, 2002
• Primary Completion: January 1, 2005
• Study Completion: January 1, 2005
• Last Updated: September 23, 2009

Record last verified: 2009-09

Locations

US (2)