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

NCT02460783 | Completed Results

• 2 other identifiers: 15012315-AG-0123
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer's Disease; Obesity; Diabetes Mellitus

Keywords

Biomarkers; Diabetes; Obesity; Dementia of the Alzheimer Type; Functional Magnetic Resonance Imaging (fMRI)

Outcome Measures

Primary Outcomes (2)

• Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine312-insulin Receptor Substrate-1 (pS312-IRS-1)

  IRS-1 is an intracellular adaptor molecule that is being recruited and activated by the binding of insulin and insulin-like growth factor to their respective receptors and in insulin resistance (IR) it shows aberrant phosphorylation in serine residues resulting in impaired downstream signal propagation. pS312-IRS-1 is considered an index of brain insulin resistance and a therapeutic response biomarker for interventions targeting brain IR. A decrease in its levels indicates target engagement with the intervention and improvement in brain IR.

  Week 0, Week 4, Week 8

• Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) P-pan-Tyrosine-IRS-1 (pY-IRS-1)

  IRS-1 is an intracellular adaptor molecule that is being recruited and activated by the binding of insulin and insulin-like growth factor to their respective receptors and in insulin resistance (IR) it shows aberrant phosphorylation in tyrosine residues resulting in impaired downstream signal propagation. pY-IRS-1 is considered an index of brain insulin resistance and a therapeutic response biomarker for interventions targeting brain IR. A decrease in its levels indicates target engagement with the intervention and improvement in brain IR.

  Week 0, Week 4, Week 8

Secondary Outcomes (90)

• Mean Change in Body Weight

  Week 0, Week 8

• Mean Change in Body Mass Index (BMI)

  Week 0, Week 8

• Mean Change in Waist Circumference

  Week 0, Week 8

• Mean Change in Fasting Glucose

  Week 0, Week 8

• Mean Change in Fasting Insulin

  Week 0, Week 8

Study Arms (2)

5-2 CR

EXPERIMENTAL

Healthy living diet for 5 days/week; Calorie Restriction (480 Kcal in the form of a shake) for 2 days/week.

Other: Boost (R) 5-2 diet

Healthy Living Diet

ACTIVE COMPARATOR

Healthy living diet for 7 days/week

Other: Healthy Living Diet

Interventions

Boost (R) 5-2 diet OTHER

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.

Also known as: 5-2 Intermittent Fasting (IF)

5-2 CR

Healthy Living Diet OTHER

Counseling and educational material on diet portion, consistency

Healthy Living Diet

Eligibility Criteria

• Age: 55 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI greater than or equal to 27; in addition, weight less than or equal to 350 lbs (weight limit for MRI scanner);
• Age of 55-70 years;
• HOMA-IR greater than or equal to 1.8;
• MMSE greater than or equal to 26
• History of clinically significant cardiovascular disease for the purpose of this study, such as chronic heart failure, coronary disease, cardiomyopathy, clinically significant cardiac valvular disease or clinically significant peripheral vascular disease. Cardiovascular conditions that are clinically non-significant for the purpose of this study, such as controlled hypertension, minor EKG abnormalities, mitral valve prolapse or benign murmurs are permissible;
• History of clinically significant stroke or other neurological disease of the central nervous system;
• History of substance abuse in the past 6 months or positive urine drug screen;
• History of clinically significant endocrine disorders (common mild endocrine disorders, such as untreated subclinical hypothyroidism with TSH \< 10 mU/l or successfully treated hypothyroidism may be allowed);
• History of eating disorders, significant GI disorders or malabsorption disorders;
• History of type 2 diabetes; and/or use of anti-diabetes medications or insulin; and/or type 2 diabetes diagnosed during the screening visit based on fasting glucose \> 125 mg/dL;
• History of hypoglycemia; and/or a fasting glucose \< 70 mg/dL during the screening visit.
• Current use of systemic corticosteroids;
• Positive screening tests for HIV, HCV or HBV;
• Hematocrit less than 35% or hemoglobin less than 11 mg/dL;
• ALT or AST \> 1.5 times the upper normal limit;

Sponsors & Collaborators

• National Institute on Aging (NIA): lead

Study Sites (1)

National Institute of Aging, Clinical Research Unit

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

• Kapogiannis D, Manolopoulos A, Mullins R, Avgerinos K, Delgado-Peraza F, Mustapic M, Nogueras-Ortiz C, Yao PJ, Pucha KA, Brooks J, Chen Q, Haas SS, Ge R, Hartnell LM, Cookson MR, Egan JM, Frangou S, Mattson MP. Brain responses to intermittent fasting and the healthy living diet in older adults. Cell Metab. 2024 Aug 6;36(8):1668-1678.e5. doi: 10.1016/j.cmet.2024.05.017. Epub 2024 Jun 19.

  PMID: 38901423 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Alzheimer Disease; Obesity; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Dimitrios Kapogiannis
• Organization: National Institute on Aging

kapogiannisd@nih.mail.gov

+1-202-290-0433

Study Officials

• Dimitrios I Kapogiannis, M.D.

  National Institute on Aging (NIA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2015
• First Posted: June 2, 2015
• Study Start: June 22, 2015
• Primary Completion: January 14, 2022
• Study Completion: December 23, 2022
• Last Updated: April 2, 2024
• Results First Posted: April 2, 2024

Record last verified: 2023-11-15

Locations

US (1)