Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Overall Status

Completed

CT.gov ID

NCT00212290

Collaborator

(none)

140

Enrollment

Locations

Duration (Months)

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the effects of treating insulin resistance on memory and attention, brain glucose utilization, and proteins in spinal fluid.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance Type 2 Diabetes Mellitus	Drug: pioglitazone Drug: nateglinide Drug: placebo	Phase 4

Detailed Description

Insulin resistant conditions such as impaired glucose tolerance, type 2 diabetes mellitus, and hyperinsulinemia have been associated with an increased risk for memory decline and for Alzheimer's disease. The main study will determine whether treatment with pioglitazone or nateglinide will improve verbal memory and selective attention for older adults with impaired glucose tolerance or mild type 2 diabetes. The main study will also characterize changes in blood concentrations of insulin, inflammatory markers, and the beta-amyloid peptides that are related to Alzheimer's disease. In one sub-study, participants will undergo brain positron emission tomography (PET) imaging before and after 16 weeks of treatment with pioglitazone, nateglinide, or placebo. The purpose of this sub-study is to determine the effects of treatment on brain glucose utilization. In a second sub-study, participants will undergo a lumbar puncture procedure before and after treatment. The purpose of this sub-study is to determine the effects of treatment on spinal fluid concentrations of insulin, inflammatory markers, and beta-amyloid peptides. Together these main and sub-studies should characterize the effects of insulin resistance on cognition and suggest a mechanism by which insulin resistant conditions increase risk for memory decline and for Alzheimer's disease.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Study Start Date :

Nov 1, 2002

Actual Study Completion Date :

Dec 1, 2006

Outcome Measures

Primary Outcome Measures

Verbal memory (main study) []
Selective attention (main study) []
Plasma beta-amyloid levels (main study) []
Cerebral glucose metabolism (sub-study) []
Inflammatory markers in spinal fluid (sub-study) []
Beta-amyloid in spinal fluid (sub-study) []

Secondary Outcome Measures

Psychomotor speed []
Verbal fluency []
Blood levels of insulin, insulin degrading enzyme, cortisol and inflammatory markers []

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Impaired glucose tolerance OR mild type 2 diabetes mellitus OR normal blood sugar regulation
Stable weight and activity level

Exclusion Criteria:

Medications for diabetes
Dementia
Medications with known effects on memory
Serious neurologic disease or head trauma
Serious systemic illness (e.g., renal failure or uncontrolled hypertension)
Serious psychiatric illness (e.g., schizophrenia or bipolar disorder)
Allergy to pioglitazone or nateglinide

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Puget Sound Health Care System (Seattle Campus)	Seattle	Washington	United States	98108
2	VA Puget Sound Health Care System (American Lake Campus)	Tacoma	Washington	United States	98493