Clinical trial NCT00736996
Conditions: Mild Cognitive Impairment
Keywords: Metabolic Syndrome Mild Cognitive Impairment Insulin Resistance Endurance Exercise
Sponsor: University of Colorado, Denver
Start date: 2008-11-01; Completion date: 2013-12-01
Enrollment: 78 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to investigate novel treatments to delay progression to dementia in patients with mild cognitive impairment (MCI) and metabolic syndrome (MS). The hypothesis is that treatment with pioglitazone or endurance exercise training will improve, stabilize, or attenuate decline in cognitive function compared to controls. This study will also discover potential mechanisms for the improvements and determine the baseline prevalence of amnestic versus non-amnestic MCI.

Detailed description:
The Metabolic Syndrome (MS) is a rapidly growing public health problem. This constellation of metabolic abnormalities increases the risk of diabetes, heart disease and death. Recently evidence has linked MS with cognitive impairment and dementia, including Alzheimer's Disease (AD). AD is preceded by a state called Mild Cognitive Impairment (MCI), characterized by subjective and objective memory impairment, but no functional impairment. Although not all persons with MCI will develop AD, the conversion rate from MCI to AD is about 15% per year, or 5-10 times that of cognitively normal individuals. There is great interest in finding treatments to prevent AD by intervening at an earlier stage, i.e. MCI.

The mechanism(s) linking MS and cognitive impairment are not clear, although there is evidence that insulin resistance and inflammation play key roles. Thiazolidinediones (TZDs) are medications approved for the treatment of Type 2 Diabetes, which work by reducing insulin resistance. In addition, these drugs have anti-inflammatory properties. A recent pilot study showed improvements in some areas of cognition in patients with MCI or mild AD treated with the TZD rosiglitazone. Endurance exercise training (EET) is an established treatment for MS and insulin resistance. There is also evidence that EET may improve cognitive function as well.

Adults aged 55 years or older with both MS and MCI at baseline will be randomized to a 6-month intervention with either (1) treatment with pioglitazone, (2) endurance exercise training, or (3) control (placebo and no exercise). The hypothesis is that treatment with the TZD pioglitazone or EET will improve cognitive function compared to controls, as evidenced by either improvement, stabilization, or lesser decline in performance on cognitive testing. Participants will undergo a physical exam including blood and urine tests, a complete neurologic exam, and a comprehensive battery of cognitive tests. They will also have a DEXA scan, exercise treadmill test, non-invasive tests of vascular function and a hyperglycemic-euglycemic clamp procedure to measure insulin resistance.

Arms: arm 1: Pioglitazone

30 - 45mg tablet daily for 6 months arm 2: Endurance Exercise Training (EET) Individualized exercise prescription, 45-75 minutes (progressive increments) three times a week arm 3: Placebo matching tablet sugar pill daily for 6 months
Interventions: intervention 1: Pioglitazone intervention 2: Placebo intervention 3: Endurance Exercise Training
Intervention descriptions: intervention 1: 30 - 45mg tablet daily for 6 months intervention 2: Matching tablet daily for 6 months intervention 3: Individualized exercise prescription, 45-75 minutes (progressive increments) three times a week

Protocol documents: