Pioglitazone Or Exercise to Treat Mild Cognitive Impairment (MCI) (POEM)
|ClinicalTrials.gov Identifier: NCT00736996|
Recruitment Status : Completed
First Posted : August 18, 2008
Results First Posted : January 15, 2016
Last Update Posted : January 15, 2016
|Condition or disease||Intervention/treatment||Phase|
|Mild Cognitive Impairment||Drug: Pioglitazone Drug: Placebo Behavioral: Endurance Exercise Training||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||78 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Pioglitazone and Exercise Effects on Older Adults With MCI and Metabolic Syndrome|
|Study Start Date :||November 2008|
|Actual Primary Completion Date :||December 2013|
|Actual Study Completion Date :||December 2013|
30 - 45mg tablet daily for 6 months
30 - 45mg tablet daily for 6 months
Other Name: Actos
Active Comparator: Endurance Exercise Training
Endurance Exercise Training (EET) Individualized exercise prescription, 45-75 minutes (progressive increments) three times a week
Behavioral: Endurance Exercise Training
Individualized exercise prescription, 45-75 minutes (progressive increments) three times a week
Placebo Comparator: Placebo
Placebo matching tablet sugar pill daily for 6 months
Matching tablet daily for 6 months
- Change in Cognitive Performance [ Time Frame: Baseline to 6 months ]Participants were administered a neuropsychological testing battery consisting of assessments in four cognitive domains: memory (Visual Reproduction II, Logical Memory II, Rey Auditory Verbal Learning Test), language (Boston Naming Test , Category Fluency), visuospatial (Block Design, Picture Completion), and executive function (Trail Making Test B, Digit Symbol Test). Raw test scores for these primary cognitive domain measures were transformed into age-adjusted scaled scores with a mean of 10 and a standard deviation (SD) of 3, with higher numbers indicating better cognitive performance, using the Mayo's Older American Normative Studies data. Cognitive domain scores were calculated as the arithmetic mean of the normatively derived scaled scores for all of the tests in that domain.
- Change in Insulin Resistance [ Time Frame: Baseline to 6 months ]Change in whole body glucose disposal rate (mg/kg/min) calculated during a single-stage (40 mU/m2/min), 3-hour hyperinsulinemic, euglycemic clamp
- Change in Peak Oxygen Uptake (VO2 Peak) [ Time Frame: Baseline to 6 months ]Peak oxygen consumption (VO2 peak, ml/kg/min) was determined by open circuit spirometry during a standard treadmill stress test (modified Balke protocol).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00736996
|United States, Colorado|
|University of Colorado, Denver|
|Denver, Colorado, United States, 80045|
|Principal Investigator:||Robert S. Schwartz, MD||University of Colorado, Denver|