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

Obesity Clinical Trial

Official title: Intermittent Calorie Restriction, Insulin Resistance, and Biomarkers of Brain Function

Status Completed

Clinical Trial Summary

Background:

• Insulin removes sugar from the blood to use for energy. Insulin resistance means that cells may not respond to insulin normally. It can lead to serious diseases. Researchers want to see how diet affects insulin resistance, weight, and brain chemicals related to Alzheimer s disease.

Objectives:

• To compare two forms of diet and their effects on insulin resistance and the brain.

Eligibility:

• Women ages 55 70 with insulin resistance.

Design:

• This study requires 6 clinic visits over 9 12 weeks. Participants must fast before visits.

• Visit 1, screening:

• Medical history, physical exam, and blood and urine tests.

• Participants will get a wrist device to wear for 4 days.

• Visit 2:

• Weight and waist measurement.

• Blood drawn.

• Questionnaires and thinking tests.

• Lumbar puncture. Skin will be numbed and a needle inserted between bones in the back will remove <TAB>fluid.

• Participants will drink a nutrition shake. Blood will be taken 12 times over 4 <TAB>hours through a thin tube in <TAB>the arm.

• Brain MRI. Participants will lie on a table that slides in and out of a cylinder in a strong magnetic field. <TAB>They will have a coil on their head and may do tasks.

• Participants will get advice about healthy eating and be randomly put in one of 2 groups. One group will get <TAB>nutrition shakes to drink.

• Visits 3 5:

• Weight and waist measurements, vital signs, blood draw, and questionnaires.

• Between visits, participants will get a call or email to check how they are doing.

• Visit 6: Repeat of visit 1.

• Participants will wear the wrist device for 4 more days, have a follow-up contact, then the study is finished.

Clinical Trial Description

Being overweight or obese can cause insulin resistance (IR), which is defined as reduced responsiveness to insulin by the cells of various tissues or organs. IR at midlife increases the risk of developing Alzheimer s disease (AD). We recently discovered novel biomarkers of brain IR (altered Tyr and Ser phosphorylated forms of insulin receptor substrate 1; IRS-1) in plasma exosomes enriched for neuronal origin. Moreover, IR is associated with AD biomarkers including deficits in resting state brain activity and cognitive performance. Calorie restriction is defined as consuming fewer calories than what is considered normal without a lack of nutrients. A certain type of calorie restriction, in which one consumes 500-600 calories a day for two consecutive days, followed by non-restricted eating for 5 days (5-2 CR), has been shown to lower peripheral insulin resistance effectively. Effects of CR and lowering peripheral IR on brain IR and cognition are unknown. The goal of this exploratory pilot study is to provide proof-of-concept that 5-2 CR at midlife can reverse brain IR, lower peripheral IR, improve cognitive performance, and increase brain activation at rest and during tasks. Specifically, we will study the effects of 8 weeks of 5-2 CR versus a control dietary intervention on brain and peripheral IR, memory and executive function, resting state default mode network activity, brain metabolism, and AD biomarkers. Forty overweight to obese women and men (between 55 and 70 years of age) will be randomized 1:1 into 5-2 CR and control groups. In the 5-2 CR group, participants will be offered healthy living dietary counseling at baseline, which they will be instructed to implement for five days/week. For each of the other two consecutive days/week, they will consume two shakes (Boost , CWI Medical), providing a total of 480 Kcal/day. In the control group, participants will be offered healthy living dietary counseling at baseline, which they will be asked to implement for every day of the week. Participants will undergo screening including a history and physical examination, calculation of Body Mass Index (BMI, which must be greater than or equal to 27) and a blood draw for insulin and glucose to determine whether they have insulin resistance. If participants meet eligibility criteria, they will continue with a baseline visit involving anthropometric measures, questionnaires, tests of cognitive function, brain MRI, blood draws for plasma and peripheral blood mononuclear cells, and lumbar puncture for cerebrospinal fluid biomarkers of AD. After 8 weeks, we will collect the same measures. To assess and reinforce compliance with their respective diet, participants will come into the clinic every 2 weeks to discuss compliance, measure their body weight and perform blood draws for measurement of ketones to objectively confirm energy restriction for the 5-2 CR group. We will also contact participants every week to further ensure compliance. To assess the effects of the diets on physical activity, participants will be asked to wear an accelerometer for 96 hours before and after they are on the diet. ;

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Diabetes Mellitus
• Insulin Resistance
• Obesity

• NCT number: NCT02460783
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: N/A
• Start date: June 22, 2015
• Completion date: December 23, 2022