This trial is active, not recruiting.

Condition mild cognitive impairment
Treatment rosiglitazone
Phase phase 2
Sponsor University of Washington
Collaborator National Institute on Aging (NIA)
Start date June 2006
End date December 2011
Trial size 120 participants
Trial identifier NCT00242593, 1R01AG025502-01A1, 1RO1 AG025502-01A1, IA0087


The purpose of this study is to determine the effects of the insulin-sensitizing medication rosiglitazone on attention and memory skills in older adults with mild cognitive impairment (MCI). The study also will examine the effects of this medication on brain structures that support memory and other thinking abilities, and on biological markers associated with inflammation, insulin resistance, and cardiovascular disease.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
oral rosiglitazone 4 mg twice daily for 18 months
rosiglitazone Avandia
4 mg twice daily oral rosiglitazone or placebo pill for 18 months
(Placebo Comparator)
placebo pill twice daily for 18 months
rosiglitazone Avandia
4 mg twice daily oral rosiglitazone or placebo pill for 18 months

Primary Outcomes

Cognitive measures: delayed list recall, Stroop Interference test
time frame: every 6 months for 18 months, again 2 at months post-treatment (20 months)
Biological outcomes: plasma insulin, IDE, AB40, AB42, inflammatory cytokines, and F2-isoprostanes
time frame: every 6 months for 18 months, again 2 at months post-treatment (20 months)
MRI outcome: Whole brain and medial temporal lobe atrophy rate
time frame: baseline and 18 months

Secondary Outcomes

Cognitive measures: ADAS-cog total score, story recall verbal fluency, paired associate learning, SOPT, rating scales
time frame: every 6 months for 18 months, again 2 at months post-treatment (20 months)

Eligibility Criteria

Male or female participants at least 55 years old.

Inclusion Criteria: - MCI diagnosis: Participants will be diagnosed with MCI by consensus of a team of physicians and neuropsychologists experienced in the diagnosis of MCI, using the Petersen (Petersen, 1999, 2001) criteria for amnestic MCI or multiple domain MCI with amnestic features: a) the presence of subjective memory complaints, evaluated via detailed patient history and informant interview, b) objective verification of memory impairment as measured by neuropsychological tests, c) normal general cognitive function, d) intact or only mildly impaired activities of daily living, and e) absence of dementia per NINCDS/ADRDA and/or DSM-IV criteria Exclusion Criteria: The following exclusion criteria will be used, based on initial physical examination, medical history, lab work, and oral glucose tolerance test (OGTT) results: - Diagnosis of diabetes or other relevant glucoregulatory disorders - Use of any oral anti-diabetic compounds - Clinically significant elevations in liver function - Significant neurological disease that might affect cognition, other than MCI, including Alzheimer's disease, large-vessel stroke, Parkinson's disease, multiple sclerosis, recent severe head injury (loss of consciousness for more than 30 minutes in the past year), or remote head injury resulting in permanent cognitive or neurological sequelae - History or current evidence of congestive heart failure (CHF) - History of documented ischemic cardiac disease, i.e., angina, MI, angioplasty, stent, or CABG - History of cardiac or vascular surgery, or significant arrhythmia within the last year; or planned major intervention such as cardiac surgery or stenting. A history of cardiac surgery for non-ischemic indications (i.e., valve repair or replacement) greater than one year prior to enrollment is not exclusionary if all other criteria are met - Significant ECG abnormalities including heart rate less than 50 or greater than 100 beats per minute (dependent upon the individual's general health); any previously unrecognized arrhythmia requiring further intervention - Significant peripheral edema at the time of screening - Significant medical illness or organ failure, including but not limited to renal disease, hepatic disease, and unstable cardiac disease - Regular current use of antipsychotic, anticonvulsive, anxiolytic, or sedative medications; antidepressant medications are not exclusionary, provided the individual does not have current major depression - A current diagnosis of major depression or other significant psychiatric comorbidity - Clinically significant anemia at the time of screening - Fasting triglyceride level greater than 400 - Fasting glucose 125 or greater, or two-hour glucose value greater than 199 during the OGTT; participants will be notified if their fasting blood sugar (monitored every 3 months) exceeds 125, and they will be withdrawn from further participation if their fasting blood sugar exceeds 125 for two consecutive months - For the MRI substudy, additional exclusion criteria include 1) previous exposure to work involving the cutting or grinding of metal, 2) the presence of a pacemaker, aneurysm clip, or other implanted metal device that would prohibit MRI procedures, and 3) significant history of claustrophobia

Additional Information

Official title The Effects of Rosiglitazone on Cognition in Patients With MCI
Principal investigator Suzanne Craft, PhD
Description The study will examine the effects of the insulin-sensitizing agent rosiglitazone on learning and memory for 120 patients diagnosed with MCI. Participants will be randomized to an 18-month trial of rosiglitazone or placebo, followed by a 2-month washout period. At screening and at treatment month 18, all participants will undergo an oral glucose tolerance test (OGTT) to estimate pre- and post- treatment insulin sensitivity and β-cell function. Cognitive measures and blood samples for biochemical assays will be obtained at baseline, treatment months 6, 12, and 18, and washout (two months after completing treatment). During treatment, participants will have safety labs drawn and receive physical assessment of any adverse events, changes in health status, or changes in medication; initially these visits will be done at weeks 2 and 4, and then every three months. For months in which a safety visit is not scheduled, telephone monitoring to assess any health concerns will be conducted. All participants enrolled in the primary study will be approached to participate in an MRI substudy; patients will undergo serial brain MRI before treatment and following 18 months of rosiglitazone or placebo, using three-dimensional T1-weighted images. Comparison of MCI patients receiving rosiglitazone and placebo will be conducted to determine whether the rate of medial temporal lobe (MTL) and whole brain atrophy is altered following treatment.
Trial information was received from ClinicalTrials.gov and was last updated in August 2011.
Information provided to ClinicalTrials.gov by University of Washington.