Intermittent Calorie Restriction, Insulin Resistance, and Biomarkers of Brain Function
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|ClinicalTrials.gov Identifier: NCT02460783|
Recruitment Status : Recruiting
First Posted : June 2, 2015
Last Update Posted : April 15, 2020
- 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.
- To compare two forms of diet and their effects on insulin resistance and the brain.
- Women ages 55 70 with insulin resistance.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer's Disease Obesity Diabetes Mellitus||Other: Boost 5-2 diet Other: Healthy Living Diet||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Intermittent Calorie Restriction, Insulin Resistance, and Biomarkers of Brain Function|
|Actual Study Start Date :||June 22, 2015|
|Estimated Primary Completion Date :||July 1, 2021|
|Estimated Study Completion Date :||July 1, 2021|
Experimental: 5-2 CR
Healthy living diet for 5 days/week; Calorie Restriction(530 Kcal in the form of a shake) for 2 days/week
Other: Boost 5-2 diet
Regular diet for 5 days/week; Calorie Restriction (480 Kcal in the form of a shake) for 2 days /week. Supplement providing 240 Kcal per shake. Participant takes 2 shakes per calorie restriction day.
Active Comparator: Healthy Living
Healthy living diet for 7 days/week
Other: Healthy Living Diet
Counseling and educational material on diet portion, consistency
- Exosomal p-S312-IRS-1/p-panY-IRS-1 ratio (index of brain insulin resistance) [ Time Frame: baseline and 8 weeks ]index of brain insulin resistance
- DNA methylation [ Time Frame: Baseline, 2, 4, 6, and 8 weeks ]Genome-wide methylation in peripheral blood mononuclear cells
- Exosomal proteins and mRNA [ Time Frame: Baseliine, week 0 ]Other exosomal proteins and mRNA biomarkers of AD
- Si and HOMA-IR [ Time Frame: Screening, 8 weeks ]Indices of insulin resistance, derived from insulin and glucose values taken from a fasting blood draw
- fMRI activation to food preference task [ Time Frame: Baseline, 8 weeks ]Activation to appetitive food versus non-appetitive food stimuli
- Resting fMRI [ Time Frame: Baseline, 8 weeks ]Intrinsic functional connectivity of DMN
- fMRI activiation to Stroop [ Time Frame: Baseline, 8 weeks ]Behavioral performance and fMRI activation during Color-Word Stroop task
- MRS metabolites [ Time Frame: Baseline, 8 weeks ]Brain metabolites assessed with Magnetic Resonance spectroscopy and regional perfusion assessed with arterial spin labeling
- Cognitive performance [ Time Frame: Baseline, 8 weeks ]Memory and executive function scores
- Anthropometric measures [ Time Frame: Screening, Baseline, 2, 4, 6, and 8 weeks ]Anthropometric measures (weight, waist circumference, sagittal diameter
- Clinical labs [ Time Frame: Screening, Outcome ]Lipid panel, uric acid
- Plasma ketones [ Time Frame: Baseline, 8 weeks ]Beta-hydroxybutyrate and other metabolites
- Hormones during a mixed meal [ Time Frame: Baseline, 8 weeks ]Plasma metabolites and hormones(GLP-1, insulin) during mixed meal tolerance test
- CSF, plasma AD biomarkers [ Time Frame: Baseline, 8 weeks ]CSF and plasma AD biomarkers, including A <=1-42 and p181Tau
- Plasma and CSF neurotrophic factors [ Time Frame: Baseline, 8 weeks ]Plasma and CSF neurotrophic factors, such as BDNF
- Plasma and CSF reactive oxygen species [ Time Frame: Baseline, 8 weeks ]Plasma and CSF reactive oxygen species, advanced glycation end-products and advanced oxidation protein products
- Cytokines [ Time Frame: Baseline, 8 weeks ]Plasma and CSF proinflammatory cytokines, such as IL-6, IL-8, IL-12 and IL-23;
- Rating of symptoms [ Time Frame: Every week from 0 to 8 ]Symptoms that can occur with 5-2 CR, mood and quality of life changes, recorded during both the 5-2 CR and control diet phases
- Physical acttivity measurement [ Time Frame: Screening and week 0 ]Physical activity measured using an accelerometer
- Gene expression [ Time Frame: Baseline, 2, 4, 6, and 8 weeks ]Global gene expression pattern, mitochondria gene expression and expression of other gene pathways responding to CR
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02460783
|Contact: Kristy L Kessler, R.N.||(410) email@example.com|
|Contact: Dimitrios I Kapogiannis, M.D.||(410) firstname.lastname@example.org|
|United States, Maryland|
|National Institute of Aging, Clinical Research Unit||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Principal Investigator:||Dimitrios I Kapogiannis, M.D.||National Institute on Aging (NIA)|