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Intermittent Calorie Restriction, Insulin Resistance, and Brain Function

Recruiting

In this study, researchers will investigate how diet affects insulin resistance, weight, and brain chemicals related to Alzheimer's disease. Specifically, they will compare two forms of diet and their effects on insulin resistance and the brain.

Minimum Age Maximum Age Gender Healthy Volunteers
55 Years 70 Years Both Yes
June 2015
July 1, 2021
150

  • Body Mass Index (BMI) greater than or equal to 27
  • Weight less than or equal to 350 pounds
  • HOMA-IR greater than or equal to 1.8
  • Mini-Mental State Examination score greater than or equal to 26

  • History of cardiovascular disease, clinically significant stroke, or other neurological disease
  • History of substance abuse in the past 6 months or positive urine drug test
  • History of clinically significant endocrine disorders (common mild endocrine disorders or successfully treated hypothyroidism may be allowed)
  • History of eating disorders, significant gastrointestinal disorders, or malabsorption disorders
  • History of type 2 diabetes, use of diabetes medications or insulin, and/or type 2 diabetes diagnosed during screening
  • History of hypoglycemia and/or a fasting glucose level of <70 mg/dL during screening
  • Current use of systemic corticosteroids
  • Positive screening tests for HIV, HCV or HBV; hematocrit less than 35 percent or hemoglobin less than 11 mg/dL; ALT or AST >1.5 times the upper normal limit
  • Contraindications to MRI (such as pacemakers, ferrous metal implants, or shrapnel in or around the head)
  • Contraindications to lumbar puncture such as taking warfarin or coagulopathy; low-dose aspirin is allowed
  • Pregnancy or nursing
  • Refusal to consent to genetic testing

Being overweight or obese can cause insulin resistance (IR)reduced responsiveness to insulin by the cells of various tissues or organs. IR at midlife increases the risk of developing Alzheimer's disease and is associated with Alzheimer's biomarkers.

Calorie restriction means consuming fewer calories than normal without a lack of nutrients. A certain type of calorie restriction, in which one consumes 500-600 calories a day for 2 consecutive days, followed by nonrestricted eating for 5 days (5-2 CR), has been shown to lower peripheral IR. Effects of calorie restriction and lowering peripheral IR on brain IR and cognition are unknown.

The goal of this exploratory pilot study is to show that a 5-2 CR diet at midlife can reverse brain IR, lower peripheral IR, improve cognitive performance, and increase brain activation at rest and during tasks. Participants will be assigned to either an intervention group or a control group. The intervention group will adopt a 5-2 CR diet for 8 weeks. The control group will eat a normal, unrestricted diet. Both groups will receive dietary counseling at the start of the study.

Screening includes a medical history and physical examination, calculation of BMI, and a blood draw to determine whether a participant has insulin resistance. Participants who meet eligibility criteria will continue with a baseline visit involving anthropometric measures, questionnaires, cognitive tests, a brain scan, blood draws, and lumbar puncture. After 8 weeks, investigators will conduct the same tests.

Participants will visit the clinic every 2 weeks to discuss compliance, get weighed, and have a blood draw to confirm energy restriction for the 5-2 CR group. Participants will wear an accelerometer, which measures physical activity, for 96 hours before and after they are on the diet.

Name City State Zip Status Primary Contact
National Institute of Aging, Clinical Research Unit
Baltimore Maryland 21224 Recruiting

National Institute on Aging (NIA)

Name Role Affiliation
Dimitrios I. Kapogiannis, MD Principal Investigator National Institute on Aging (NIA)

Name Phone Email
Kristy Kessler, RN 410-350-7319 kristy.kessler@nih.gov

NCT02460783

Intermittent Calorie Restriction, Insulin Resistance, and Biomarkers of Brain Function