Pioglitazone Or Exercise to Treat Mild Cognitive Impairment (MCI) (POEM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by University of Colorado, Denver.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00736996
First received: August 14, 2008
Last updated: October 10, 2012
Last verified: October 2012

August 14, 2008
October 10, 2012
November 2008
January 2013   (final data collection date for primary outcome measure)
Changes in cognitive performance on tests of (1) Memory, (2) Language, (3) Attention/Executive Function, and (4) Visuospatial Function [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00736996 on ClinicalTrials.gov Archive Site
Insulin resistance, measured by the hyperglycemic-euglycemic clamp procedure, and whether any improvements are correlated with corresponding improvements in cognition [ Time Frame: baseline and at 6 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Pioglitazone Or Exercise to Treat Mild Cognitive Impairment (MCI)
Pioglitazone and Exercise Effects on Older Adults With MCI and Metabolic Syndrome

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Mild Cognitive Impairment
  • Drug: Pioglitazone
    30 - 45mg tablet daily for 6 months
    Other Name: Actos
  • Drug: Placebo
    Matching tablet daily for 6 months
  • Behavioral: Endurance Exercise Training
    Individualized exercise prescription, 45-75 minutes (progressive increments) three times a week
  • Experimental: Pioglitazone

    Pioglitazone

    30 - 45mg tablet daily for 6 months

    Intervention: Drug: Pioglitazone
  • Active Comparator: Endurance Exercise Training
    Endurance Exercise Training (EET) Individualized exercise prescription, 45-75 minutes (progressive increments) three times a week
    Intervention: Behavioral: Endurance Exercise Training
  • Placebo Comparator: Placebo
    Placebo matching tablet sugar pill daily for 6 months
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
300
January 2013
January 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Community-dwelling, over 55 years old, able to give full informed consent, willing to be randomized
  • Able to perform a telephone interview
  • Able to speak, read and understand English
  • Potential volunteers on a statin drug, angiotensin converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARB), non-steroidal anti-inflammatory drug (NSAID), or Vitamin E supplement, are eligible but must be on a stable dose for at least 2 months
  • Women must be post-menopausal, as defined by no menses for 12 months
  • Must meet 3 of the 5 requirements for Metabolic Syndrome:

    • Waist measurement: greater than 102 cm for men and 88 cm for women
    • Fasting hypertriglyceridemia: 150 mg/dl (1.7 mmol/L) or higher
    • Low HDL cholesterol: less than 40 mg/dl (1.0 mmol/L) for men and 50 mg/dl (1.3 mmol/L) for women
    • Hypertension: higher than 130 mmHg systolic or 85 mmHg diastolic (average of 2 seated measurements) or currently using an antihypertensive medication
    • Elevated (untreated) fasting glucose: 100 mg/dl (5.6 mmol/L) or higher
  • Meet the study's 4-step screening process for MCI (to rule out dementia)

Exclusion Criteria:

  • Diagnosis of diabetes mellitus (DM), defined as: Fasting Blood Sugar 126 or higher, a history of known DM, or treatment with any glucose lowering medication
  • Current diagnosis of dementia (or MMSE less than 24) or a neurological co-morbidity other than MCI that might affect cognition including: large vessel stroke, brain tumor, severe brain injury, multiple sclerosis, or Parkinson's disease
  • Current diagnosis of depression assessed by a Centers for Epidemiologic Studies Depression Scale (CES-D) score of 36 or less
  • Major psychiatric conditions such as bipolar disorder, psychosis, schizophrenia, or alcoholism that could affect the ability to understand and/or cooperate fully with the protocol
  • Significant cerebral vascular disease
  • Modified Hachinski score greater than 4
  • Pregnant, lactating or having child bearing potential
  • Concomitant medications with significant cholinergic or anticholinergic effects or adverse effects on cognition including: antipsychotics, tricyclic antidepressants, anticonvulsants, sedative/hypnotics, anxiolytics, glucocorticoids (chronic or frequent intermittent), gingko biloba, NMDA receptor antagonists, cholinesterase inhibitors, strongly lipid soluble beta blockers (e.g., propranolol)
  • Hormone replacement therapy (male or female)
  • Visual/hearing impairment that would significantly impact the ability to undergo psychometric testing
  • Significant medical illness or organ failure including hepatic or renal failure, unstable cardiac disease, or life expectancy less than 18 months
  • Exercise-limiting conditions including: neuromuscular, joint/bone, cardiovascular, peripheral vascular, cerebrovascular or pulmonary disease; recent MI, pulmonary embolus, significant aortic stenosis; or exercise limiting obesity
  • Untreated B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowable)
  • Uncontrolled hypertension: over 160 mmHg systolic or 100 mmHg diastolic (stable treatment is allowable)
  • Endurance exercise training more than twice a week for 20 minutes (at a level that produces sweating) consistently during the last 6 months
  • Unstable weight in the last 6 months
  • Increased risk for Pio toxicity including: a) baseline liver dysfunction (over 2.5xULN for AST, ALT); b) hematocrit less than 33% men or 30% women; c) problematic edema; or d) congestive heart failure NYHA class II or greater
  • Stage 5 renal impairment (GFR less than 15 or dialysis)
  • Already taking a TZD or other drug that would modify insulin resistance (e.g. metformin), or has taken a TZD in the past and experienced a significant adverse effect or allergy
  • Currently taking any of following medications that may interact with Pio metabolism: atorvastatin at 80mg/day (lower doses are allowed), and medications with major CYP 3A4 inhibiting effects, such as nefazodone or systemic antifungal agents
  • Participating in another clinical trial
Both
55 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00736996
07-1215, R01AG028746
No
University of Colorado, Denver
University of Colorado, Denver
National Institute on Aging (NIA)
Principal Investigator: Robert S. Schwartz, MD University of Colorado, Denver
University of Colorado, Denver
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP