Clinical trial NCT00212290: Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Insulin Resistance
Type 2 Diabetes Mellitus
Keywords: impaired glucose tolerance
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
First posted: 2005-09-21
Enrollment: 140
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Verbal memory (main study)
measure: Selective attention (main study)
measure: Plasma beta-amyloid levels (main study)
measure: Cerebral glucose metabolism (sub-study)
measure: Inflammatory markers in spinal fluid (sub-study)
measure: Beta-amyloid in spinal fluid (sub-study)
Secondary outcomes:
measure: Psychomotor speed
measure: Verbal fluency
measure: Blood levels of insulin, insulin degrading enzyme, cortisol and inflammatory markers
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care System (Seattle Campus)
state: Washington
city: Tacoma
country: United States
facility: VA Puget Sound Health Care System (American Lake Campus)
state: Washington
Study officials:
affiliation: VA Puget Sound Health Care System, University of Washington
name: Suzanne Craft, PhD
role: PRINCIPAL_INVESTIGATOR
References: