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.

Condition	Intervention	Phase
Mild Cognitive Impairment	Drug: Rosiglitazone	Phase II

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

Primary Outcomes: Cognitive measures: delayed list recall, Stroop Interference test; Biological outcomes: plasma insulin, IDE, AB40, AB42, inflammatory cytokines, and F2-isoprostanes; MRI outcome: Whole brain and medial temporal lobe atrophy rate
Secondary Outcomes: Cognitive measures: ADAS-cog total score, story recall verbal fluency, paired associate learning, SOPT, rating scales
Expected Total Enrollment:  120

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 and urine 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 monthly. For monthly safety checks, participants may choose to come to the clinic site, or to have a phlebotomist come to their home to draw blood, with the study nurse conducting the physical assessment via telephone.

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.

Ages Eligible for Study:  55 Years and above,  Genders Eligible for Study:  Both

Criteria

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, lab work, and OGTT results:

• Diagnosis of diabetes or other relevant glucoregulatory disorders
• Use of any oral antidiabetic 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, or severe head injury
• 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
• A current diagnosis of major depression or other significant psychiatric comorbidity
• Fasting glucose greater than 165 or two-hour glucose value greater than or equal to 200 during the OGTT
• Participants will be notified if their fasting blood sugar (monitored monthly) exceeds 150, and they will be withdrawn from further participation if their fasting blood sugar exceeds 165 for two consecutive months
• Participants taking a stable dose of cholinesterase inhibitors will not be excluded from study participation; however, if, during the course of the study, the decision is made to begin treatment with such medications or to increase/decrease the medication dose, their participation will be discontinued

For the MRI substudy, additional exclusion criteria include:

• Previous exposure to work involving the cutting or grinding of metal
• The presence of a pacemaker, aneurysm clip, or other implanted metal device
• Significant history of claustrophobia

Please refer to this study by ClinicalTrials.gov identifier  NCT00242593

Brenna Cholerton, PhD      253-582-8440  Ext. 76162    bchol@u.washington.edu

Washington
      University of Washington/VA Puget Sound Health Care System, Seattle/Tacoma,  Washington,  98108,  United States
      Group Health Cooperative Center for Health Studies, Seattle,  Washington,  98108,  United States

Study chairs or principal investigators

Suzanne Craft, PhD,  Principal Investigator,  University of Washington/VA Puget Sound Health Care System   

Study ID Numbers:  IA0087; 1RO1 AG025502-01A1
Last Updated:  December 8, 2005
Record first received:  October 19, 2005
ClinicalTrials.gov Identifier:  NCT00242593
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2006-01-10