Pioglitazone Or Exercise to Treat Mild Cognitive Impairment (MCI)

NCT00736996 | Completed Phase 2 Results

• 2 other identifiers: 07-1215R01AG028746
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment

Keywords

Metabolic Syndrome; Mild Cognitive Impairment; Insulin Resistance; Endurance Exercise

Outcome Measures

Primary Outcomes (1)

• Change in Cognitive Performance

  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.

  Baseline to 6 months

Secondary Outcomes (2)

• Change in Insulin Resistance

  Baseline to 6 months

• Change in Peak Oxygen Uptake (VO2 Peak)

  Baseline to 6 months

Study Arms (3)

Pioglitazone

EXPERIMENTAL

Pioglitazone 30 - 45mg tablet daily for 6 months

Drug: Pioglitazone

Endurance Exercise Training

ACTIVE COMPARATOR

Endurance Exercise Training (EET) Individualized exercise prescription, 45-75 minutes (progressive increments) three times a week

Behavioral: Endurance Exercise Training

Placebo

PLACEBO COMPARATOR

Placebo matching tablet sugar pill daily for 6 months

Drug: Placebo

Interventions

Pioglitazone DRUG

30 - 45mg tablet daily for 6 months

Also known as: Actos

Pioglitazone

Placebo DRUG

Matching tablet daily for 6 months

Placebo

Endurance Exercise Training BEHAVIORAL

Individualized exercise prescription, 45-75 minutes (progressive increments) three times a week

Endurance Exercise Training

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Colorado, Denver

Denver, Colorado, 80045, United States

Location

Related Publications (5)

• Kramer AF, Erickson KI, Colcombe SJ. Exercise, cognition, and the aging brain. J Appl Physiol (1985). 2006 Oct;101(4):1237-42. doi: 10.1152/japplphysiol.00500.2006. Epub 2006 Jun 15.

  PMID: 16778001 BACKGROUND

• Yaffe K, Kanaya A, Lindquist K, Simonsick EM, Harris T, Shorr RI, Tylavsky FA, Newman AB. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004 Nov 10;292(18):2237-42. doi: 10.1001/jama.292.18.2237.

  PMID: 15536110 BACKGROUND

• Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? J Alzheimers Dis. 2005 Feb;7(1):63-80. doi: 10.3233/jad-2005-7107.

  PMID: 15750215 BACKGROUND

• Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, Fishel MA, Kulstad JJ, Green PS, Cook DG, Kahn SE, Keeling ML, Craft S. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriatr Psychiatry. 2005 Nov;13(11):950-8. doi: 10.1176/appi.ajgp.13.11.950.

  PMID: 16286438 BACKGROUND

• Lytle ME, Vander Bilt J, Pandav RS, Dodge HH, Ganguli M. Exercise level and cognitive decline: the MoVIES project. Alzheimer Dis Assoc Disord. 2004 Apr-Jun;18(2):57-64. doi: 10.1097/01.wad.0000126614.87955.79.

  PMID: 15249848 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Metabolic Syndrome; Insulin Resistance

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Robert S. Schwartz, M.D.
• Organization: University of Colorado

robert.schwartz@ucdenver.edu

303-724-1919

Study Officials

• Robert S. Schwartz, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2008
• First Posted: August 18, 2008
• Study Start: November 1, 2008
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 15, 2016
• Results First Posted: January 15, 2016

Record last verified: 2015-12

Locations

US (1)