N/A
N=46
Intermittent Calorie Restriction, Insulin Resistance, and Biomarkers of Brain Function
Alzheimer's Disease · Obesity · Diabetes Mellitus
Bottom Line
View on ClinicalTrials.gov: NCT02460783 ↗Enrolled (actual)
46
Serious AEs
0.0%
Results posted
Apr 2024
Primary outcome: Primary: Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine312-insulin Receptor Substrate-1 (pS312-IRS-1) — 79.01; 443.72; -337.70; -608.92 pg/mL
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- Boost (R) 5-2 diet (Other); Healthy Living Diet (Other)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- All
- Sponsor
- National Institute on Aging (NIA)
- Primary completion
- Jan 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine312-insulin Receptor Substrate-1 (pS312-IRS-1) |
79.01; 443.72; -337.70; -608.92 | — |
| PRIMARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) P-pan-Tyrosine-IRS-1 (pY-IRS-1) |
5.05; 33.88; -24.72; -54.23 | — |
| SECONDARY Mean Change in Body Weight |
-4.06; -2.33 | — |
| SECONDARY Mean Change in Body Mass Index (BMI) |
-1.41; -0.80 | — |
| SECONDARY Mean Change in Waist Circumference |
-2.84; -1.64 | — |
| SECONDARY Mean Change in Fasting Glucose |
0.57; 2.16 | — |
| SECONDARY Mean Change in Fasting Insulin |
-4.48; -2.87 | — |
| SECONDARY Mean Change in Homeostatic Model Assessment of Insulin Resistance 2 (HOMA2-IR) |
-0.49; -0.33 | — |
| SECONDARY Mean Change in Glycosylated Hemoglobin (HbA1c) |
-0.20; -0.02 | — |
| SECONDARY Mean Change in White Blood Cells (WBCs) |
-0.31; -0.23 | — |
| SECONDARY Mean Change in Red Blood Cells (RBCs) |
-0.12; -0.04 | — |
| SECONDARY Mean Change in Platelets |
2.18; 8.07 | — |
| SECONDARY Mean Change in Hemoglobin |
-0.29; -0.143 | — |
| SECONDARY Mean Change in Hematocrit |
-1.08; -0.20 | — |
| SECONDARY Mean Change in International Normalized Ratio (INR) |
0.02; 0.02 | — |
| SECONDARY Mean Change in Serum Beta-Hydroxybutyrate (bHB) |
0.06; 0.03 | — |
| SECONDARY Mean Change in Serum Acetoacetate (AcAc) |
0.03; 0.01 | — |
| SECONDARY Mean Change in Serum Non-Esterified Fatty Acids (NEFA) |
0.09; 0.07 | — |
| SECONDARY Mean Change in Serum Cortisol |
22.89; 25.04 | — |
| SECONDARY Mean Change in Creatinine |
-0.01; -0.02 | — |
| SECONDARY Mean Change in Blood Urea Nitrogen (BUN) |
-0.72; -0.55 | — |
| SECONDARY Mean Change in Alanine Aminotransferase (ALT) |
-2.33; -0.77 | — |
| SECONDARY Mean Change in Aspartate Aminotransferase (AST) |
0.87; 2.95 | — |
| SECONDARY Mean Change in Total Cholesterol |
-23.16; -16.29 | — |
| SECONDARY Mean Change in HDL Cholesterol |
-3.11; -4.01 | — |
| SECONDARY Mean Change in LDL Cholesterol |
-18.31; -11.59 | — |
| SECONDARY Mean Change in Triglycerides |
-9.61; -6.61 | — |
| SECONDARY Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42 |
-43.56; -30.16 | — |
| SECONDARY Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 40 |
-608.42; -117.75 | — |
| SECONDARY Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42 / Amyloid Beta 40 Ratio |
-0.0005; -0.004 | — |
| SECONDARY Mean Change in Cerebrospinal Fluid (CSF) Total Tau |
-13.45; -3.61 | — |
| SECONDARY Mean Change in Cerebrospinal Fluid (CSF) p181-Tau |
-5.23; -1.82 | — |
| SECONDARY Mean Change in Cerebrospinal Fluid (CSF) Neurogranin |
16.32; 2.70 | — |
| SECONDARY Mean Change in Cerebrospinal Fluid (CSF) Light Chain Neurofilaments (Nf-L) |
134.31; 30.23 | — |
| SECONDARY Mean Change in Cerebrospinal Fluid (CSF) Glial Fibrillary Acidic Protein (GFAP) |
1748.07; 627.26 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 |
-10.82; -9.58; -0.62; 10.61 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 40 |
-16.92; -4.84; 11.47; 15.14 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 / Amyloid Beta 40 Ratio |
0.01; -0.03; -0.02; 0.01 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Total Tau |
-3.05; -5.33; 8.00; 20.31 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p181-Tau |
1.70; 1.01; -1.65; 9.90 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p231-Tau |
-3.47; -5.60; -2.12; 0.13 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Akt |
1.30; -3.27; -2.15; -0.48 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) |
-1.73; -5.13; -3.33; -0.93 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) / Akt Ratio |
-0.02; -0.01; -0.01; -0.003 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Extracellular Signal-regulated Kinase 1/2 (pERK1/2) |
4.66; -2.23; -2.66; 0.37 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated c-Jun N-terminal Kinase (pJNK) |
2.91; -2.88; -1.44; 8.44 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated p38 (pp38) |
5.76; -1.39; -12.20; 21.81 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) proBDNF |
-723.76; -91.37; 531.01; -388.59 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) BDNF |
0.01; 1.07; 0.98; 0.65 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Neurogranin |
5.69; 1.08; -5.43; 4.07 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Heavy Chain Neurofilaments (Nf-H) |
-25.12; 4.80; -1.59; 54.71 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) A-synuclein |
-4.21; -27.97; 1.57; 17.06 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) TAR DNA-binding Protein 43 (TDP-43) |
-443.207; 67.84; 64.67; 89.56 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 1 (MCT1) |
158.32; -104.39; -5.01; -141.72 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 2 (MCT2) |
1.27; -1.72; -0.67; 1.86 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex IV Quantity |
0.00037; -0.00006; -0.00051; -0.00002 | — |
| SECONDARY Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex V Quantity |
0.000082; 0.00019; 0.00006; -0.000074 | — |
| SECONDARY Mean Change in Glucose by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.086; -0.013 | — |
| SECONDARY Mean Change in N-acetyl-aspartate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.028; 0.054 | — |
| SECONDARY Mean Change in Lactate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.016; -0.012 | — |
| SECONDARY Mean Change in Glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.014; 0.008 | — |
| SECONDARY Mean Change in Gamma-Aminobutyric Acid (GABA) by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
0.002; 0.020 | — |
| SECONDARY Mean Change in Glutamine by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.052; -0.004 | — |
| SECONDARY Mean Change in Glutathione by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.010; -0.018 | — |
| SECONDARY Mean Change in Myo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.046; -0.012 | — |
| SECONDARY Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.038; 0.013 | — |
| SECONDARY Mean Change in Ascorbate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.107; -0.076 | — |
| SECONDARY Mean Change in Alanine by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
-0.006; -0.017 | — |
| SECONDARY Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC) |
0.002; 0.004 | — |
| SECONDARY Mean Change in Glucose by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
-0.002; 0.065 | — |
| SECONDARY Mean Change in Lactate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
0.012; -0.017 | — |
| SECONDARY Mean Change in Glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
0.010; -0.088 | — |
| SECONDARY Mean Change in Glutamine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
-0.042; -0.048 | — |
| SECONDARY Mean Change in Glutathione by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
-0.011; 0.030 | — |
| SECONDARY Mean Change in Myo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
0.001; -0.006 | — |
| SECONDARY Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
0.001; 0.042 | — |
| SECONDARY Mean Change in Ascorbate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
-0.039; 0.006 | — |
| SECONDARY Mean Change in Alanine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
-0.009; 0.001 | — |
| SECONDARY Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) |
-0.002; 0.004 | — |
| SECONDARY Mean Change in Executive Function Composite |
0.23; 0.07 | — |
| SECONDARY Mean Change in California Verbal Learning Test (CVLT) |
4.55; 4.55; 0.75; 1.40; 0.85; 0.75 | — |
| SECONDARY Mean Change in Logical Memory (LM) Test |
1.60; 1.10; 1.65; 1.75; 1.30; 2.80 | — |
| SECONDARY Change in the Positive and Negative Affect Schedule (PANAS) |
-2.45; -1.35; 0.51; -0.06 | — |
| SECONDARY Mean Change in the Short Form 36-item Health Survey (SF-36) |
2.50; 2.00; 1.25; 0.00; -5.00; 0.00 | — |
| SECONDARY Mean Change in Total Energy Expenditure |
-538.44; -302.86 | — |
| SECONDARY Mean Change in Daily Energy Expenditure |
-18.76; -175.79 | — |
| SECONDARY Mean Change in Hourly Energy Expenditure |
0.23; -9.17 | — |
| SECONDARY Mean Change in Metabolic Rate |
0.01; -0.07 | — |
| SECONDARY Mean Change in Time in Activity |
-0.013; 0.033; 0.008; -0.019; 0.005; -0.015 | — |
| SECONDARY Mean Change in Total Steps |
-4821.93; -2937.65 | — |
| SECONDARY Mean Change in Steps Per Minute |
-0.13; -1.20 | — |
| SECONDARY Mean Change in Total Sedentary Bouts |
-17.69; 13.41 | — |
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 fluid.
* Participants will drink a nutrition shake. Blood will be taken 12 times over 4 hours through a thin tube in the arm.
* Brain MRI. Participants will lie on a table that slides in and out of a cylinder in a strong magnetic field. 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 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.
Eligibility Criteria
- INCLUSION CRITERIA:
- 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
EXCLUSION CRITEIRA:
- 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 125 mg/dL;
- History of hypoglycemia; and/or a fasting glucose 1.5 times the upper normal limit;
- Contraindications for MRI (pacemakers, ferrous metal implants or shrapnel in or around the head, etc.).
- Contraindications to LP, such as Coumadin, coagulopathy (international normalized ratio, or INR > 1.5; prothrombin time (PT), partial prothrombin time (PTT) > 1.5 x upper normal limit). Aspirin 81 mg qd is allowed. Aspirin up to 325 mg qd is allowed, if withheld for 7 days prior to the LP.
- Pregnancy or nursing.
- Refusal to consent to genetic testing for APOE.
Data sourced from ClinicalTrials.gov (NCT02460783). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.