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The CALERIE™ Legacy Study

Legacy Effects of CALERIE™, a 2-year Calorie Restriction Intervention, on Hallmarks of Healthspan and Aging

Status
Active, not recruiting
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT05651620
Enrollment
216
Registered
2022-12-15
Start date
2023-04-06
Completion date
2028-01-31
Last updated
2026-06-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Calorie Restriction

Keywords

calorie restriction, dietary intervention, biological aging, behavioral data

Brief summary

The purpose of the CALERIE Legacy Study is to follow up on the health and wellness of participants from phase 2 of the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, which was conducted from 2007 to 2011.

Detailed description

The CALERIE Legacy Study is an observational follow-up study of participants from phase 2 the CALERIE trial, the first randomized controlled trial of calorie restriction (CR) in humans without obesity. The overarching goal of the CALERIE Legacy Study is to examine whether two years of CR results in sustained improvements in the biological, phenotypic, and functional hallmarks of human aging 10 to 15 years after the structured intervention. Participants will complete clinical assessments, dietary recalls, and questionnaires, and laboratory evaluations will be performed on blood and urine samples. The study also includes an optional biospecimen banking component.

Interventions

None listed

Sponsors

Tufts University
Lead SponsorOTHER
Pennington Biomedical Research Center
CollaboratorOTHER
Washington University School of Medicine
CollaboratorOTHER
Duke University
CollaboratorOTHER
National Institute on Aging (NIA)
CollaboratorNIH

Study design

Observational model
CASE_CONTROL
Time perspective
OTHER

Eligibility

Sex/Gender
ALL
Age
33 Years to 70 Years
Healthy volunteers
Yes

Inclusion criteria

* Enrolled in the CALERIE trial and started their allocated group (CR intervention or ad libitum control condition) * Willing and able to attend one of the clinical sites for an in-person visit and provide informed consent

Exclusion criteria

* Pregnant women * Women less than 12 months postpartum * Documented note from the CALERIE trial indicating that the subject should not be contacted or requested not to be contacted for future research * Diagnosed active cancer or terminal illness

Design outcomes

Primary

MeasureTime frameDescription
Biological age - Klemera-Doubal Method11-16 years post CALERIE trialBiological age will be quantified by the Klemera-Doubal Method (KDM), an algorithm-based measure. Biological age is expressed in years.
Healthspan11-16 years post CALERIE trialHealthspan will be assessed by sex-specific metabolic syndrome z-score (MS z-score). MS z-score was developed using high density lipoprotein cholesterol (HDL), triglycerides (TG), waist circumference (WC), fasting blood glucose (FBG), and mean arterial pressure (MAP = \[systolic blood pressure + 2 x diastolic blood pressure\]/3). SDs for HDL and WC in the equations are sex specific. Women: MS z-score = \[45-HDL\]/SDHDLW+ \[TG-150\]/SDTG + \[WC-88\]/SDWCW + \[FBG-100\]/SDFBG + \[MAP -100\]/SDMAP Men: MS z-score = \[40-HDL\]/SDHDLM+ \[TG-150\]/SDTG + \[WC-102\]/SDWCM + \[FBG-100\]/SDFBG + \[MAP -100\]/SDMAP W = women M = men This score does not have a unit.

Secondary

MeasureTime frameDescription
Biological age - Homeostatic Dysregulation11-16 years post CALERIE trialBiological age will be quantified by homeostatic dysregulation, an algorithm-based measure. Biological age is expressed in years.
Biological age - Levine Phenotypic Age11-16 years post CALERIE trialBiological age will be quantified by Levine Phenotypic Age, an algorithm-based measure. Biological age is expressed in years.
Height11-16 years post CALERIE trialHeight will be measured in cm.
Weight11-16 years post CALERIE trialWeight will be measured in kg.
Waist circumference11-16 years post CALERIE trialWeight circumference will be measured in cm.
Hip circumference11-16 years post CALERIE trialHip circumference will be measured in cm.
Body mass index (BMI)11-16 years post CALERIE trialBMI (kg/m2) will be calculated using height and weight measurements.
Blood pressure11-16 years post CALERIE trialSystolic and diastolic blood pressure will be measured in mmHg.
Pulse rate at rest11-16 years post CALERIE trialPulse rate will be measured in beats/min.
Respiration rate at rest11-16 years post CALERIE trialRespiration rate will be measured in breaths/min.
Fat mass11-16 years post CALERIE trialWhole-body fat mass (kg, %) as measured by dual-energy X-ray absorptiometry.
Fat-free mass11-16 years post CALERIE trialWhole-body fat-free mass (kg, %) as measured by dual-energy X-ray absorptiometry.
Bone mineral content11-16 years post CALERIE trialWhole-body bone mineral content (g) as measured by dual-energy X-ray absorptiometry.
Resting metabolic rate (RMR)11-16 years post CALERIE trialRMR will be measured in kcal/d by indirect calorimetry using a ventilated hood system.
Respiratory quotient (RQ)11-16 years post CALERIE trialRQ will be measured by indirect calorimetry using a ventilated hood system. This is a ratio (V̇CO2/V̇O2) and does not have a unit.
Maximal aerobic capacity (V̇O2max)11-16 years post CALERIE trialMaximal aerobic capacity (V̇O2max) will be measured in mL/kg/min using the Cornell incremental treadmill test.
Interleukin-6 (IL-6)11-16 years post CALERIE trialIL-6, a blood-based biomarker of aging proposed by the Targeting Aging with MEtformin (TAME) Biomarkers Workgroup, will be measured in pg/mL.
Insulin - TAME panel11-16 years post CALERIE trialInsulin, a blood-based biomarker of aging proposed by the TAME Biomarkers Workgroup, will be measured in μIU/mL.
Insulin - 0 min (OGTT)11-16 years post CALERIE trialInsulin (μIU/mL) will be measured at 0 minutes (pre-dose) during an oral glucose tolerance test (OGTT) to evaluate glucoregulatory response.
Insulin - 30 min (OGTT)11-16 years post CALERIE trialInsulin (μIU/mL) will be measured at 30 minutes post dose during an OGTT to evaluate glucoregulatory response.
Insulin - 60 min (OGTT)11-16 years post CALERIE trialInsulin (μIU/mL) will be measured at 60 minutes post dose during an OGTT to evaluate glucoregulatory response.
Insulin - 90 min (OGTT)11-16 years post CALERIE trialInsulin (μIU/mL) will be measured at 90 minutes post dose during an OGTT to evaluate glucoregulatory response.
Insulin - 120 min (OGTT)11-16 years post CALERIE trialInsulin (μIU/mL) will be measured at 120 minutes post dose during an OGTT to evaluate glucoregulatory response.
Insulin-like growth factor 1 (IGF-1)11-16 years post CALERIE trialIGF-1, a blood-based biomarker of aging proposed by the TAME Biomarkers Workgroup, will be measured in ng/mL.
Hemoglobin A1c (HbA1c)11-16 years post CALERIE trialHbA1c, a blood-based biomarker of aging proposed by the TAME Biomarkers Workgroup, will be measured in mmol/mol.
Tumor necrosis factor α receptor II (TNFRII)11-16 years post CALERIE trialTNFRII, a blood-based biomarker of aging proposed by the TAME Biomarkers Workgroup, will be measured in ng/mL.
High-sensitivity C-reactive protein (hsCRP)11-16 years post CALERIE trialhsCRP, a blood-based biomarker of inflammation, will be measured in μg/mL.
Growth/differentiation factor 15 (GDF15)11-16 years post CALERIE trialGDF15, a blood-based biomarker of aging proposed by the TAME Biomarkers Workgroup, will be measured in pg/mL.
Cystatin C11-16 years post CALERIE trialCystatin C, a blood-based biomarker of aging proposed by the TAME Biomarkers Workgroup, will be measured in mg/L.
N-terminal B-type natriuretic peptide (NT-proBNP)11-16 years post CALERIE trialNT-proBNP, a blood-based biomarker of aging proposed by the TAME Biomarkers Workgroup, will be measured in pg/mL.
Senescence-associated secretory phenotype (SASP) proteins11-16 years post CALERIE trialSASP proteins, blood-based biomarkers of cellular senescence, will be measured using a SASP panel.
Urinary Isoprostanes - iPF(2α)-III11-16 years post CALERIE trialUrinary iPF(2α)-III, a biomarker of systemic oxidative stress, will be measured in ng/mL.
Urinary Isoprostanes - 2,3-dinor-iPF(2α)-III11-16 years post CALERIE trialUrinary 2,3-dinor-iPF(2α)-III, a biomarker of systemic oxidative stress, will be measured in ng/mL.
Urinary Isoprostanes - iPF(2α)-VI11-16 years post CALERIE trialUrinary iPF(2α)-VI, a biomarker of systemic oxidative stress, will be measured in ng/mL.
Urinary Isoprostanes - 8,12-iso-iPF(2α)-VI11-16 years post CALERIE trialUrinary 8,12-iso-iPF(2α)-VI, a biomarker of systemic oxidative stress, will be measured in ng/mL.
Creatinine11-16 years post CALERIE trialCreatinine, a byproduct of routine activity in the muscle, will be measured in urine in mg/mL.
Dehydroepiandrosterone (DHEA)11-16 years post CALERIE trialDHEA, a blood-based steroid hormone, will be measured in μg/dL.
Interleukin 1 beta (IL-1b)11-16 years post CALERIE trialIL-1b, a blood-based marker of inflammation, will be measured in pg/mL.
Interleukin 8 (IL-8)11-16 years post CALERIE trialIL-8, a blood-based marker of inflammation, will be measured in pg/mL.
Tumor necrosis factor α (TNF-α)11-16 years post CALERIE trialTNF-α, a blood-based marker of inflammation, will be measured in pg/mL.
Insulin-like growth factor-binding protein 1 (IGFBP-1)11-16 years post CALERIE trialIGFBP-1, a blood-based transport protein, will be measured in ng/mL.
Transforming growth factor beta 1 (TGFB1)11-16 years post CALERIE trialTGFB1, a blood-based marker of immune function, will be measured in ng/mL.
Insulin-like growth factor-binding protein 3 (IGFBP-3)11-16 years post CALERIE trialIGFBP-3, a blood-based transport protein, will be measured in ng/mL.
Platelet-derived growth factor-AB (PDGF-AB)11-16 years post CALERIE trialPDGF-AB, a blood-based marker of cellular function, will be measured in ng/mL.
Intercellular Adhesion Molecule 1 (ICAM-1)11-16 years post CALERIE trialICAM-1, a blood-based marker of inflammation, will be measured in ng/mL.
Growth hormone11-16 years post CALERIE trialGrowth hormone, a blood-based bio-marker of cellular function, will be measured in ng/mL.
Monocyte Chemoattractant Protein 1 (MCP1)11-16 years post CALERIE trialMCP1, a blood-based marker of inflammation, will be measured in pg/mL.
Leptin11-16 years post CALERIE trialLeptin, a hormonal regulator of energy balance, will be measured in pg/mL.
Total adiponectin11-16 years post CALERIE trialTotal adiponectin, a protein hormone that regulates several metabolic processes, including glucose regulation and fatty acid oxidation, will be measured in μg/mL.
High molecular weight adiponectin11-16 years post CALERIE trialHigh molecular weight adiponectin, a protein hormone that regulates several metabolic processes, including glucose regulation and fatty acid oxidation, will be measured in μg/mL.
Muscle strength - Knee extension (60°)11-16 years post CALERIE trialKnee extension at 60 degrees per second will be measured by isokinetic dynamometry and expressed in Nm.
Muscle strength - Knee extension (180°)11-16 years post CALERIE trialKnee extension at 180 degrees per second will be measured by isokinetic dynamometry and expressed in Nm.
Muscle strength - Knee flexion (60°)11-16 years post CALERIE trialKnee flexion at 60 degrees per second will be measured by isokinetic dynamometry and expressed in Nm.
Muscle strength - Knee flexion (180°)11-16 years post CALERIE trialKnee flexion at 180 degrees per second will be measured by isokinetic dynamometry and expressed in Nm.
Handgrip Strength11-16 years post CALERIE trialHandgrip strength will be measured via a hand dynamometer and expressed in kg.
Physical functioning11-16 years post CALERIE trialPhysical functioning as measured by a physical performance battery. This physical performance battery provides a composite score ranging from 0 to 12 and includes results from the balance, gait and chair stand tests.
Cognition11-16 years post CALERIE trialCognition as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB). The CANTAB evaluates six main areas of cognitive function: reaction time; verbal recognition memory; intra-extra dimensional set shift; rapid visual information processing; delayed matching to sample; and spatial working memory.
Dietary intake - calories11-16 years post CALERIE trialDietary intake in calories (kcals/day), as measured by multiple-pass 24-hour dietary recalls and Nutrition Data System for Research (NDSR) software.
Dietary intake - carbohydrates11-16 years post CALERIE trialDietary carbohydrates (grams and % of energy intake) will be measured by multiple-pass 24-hour dietary recalls and Nutrition Data System for Research (NDSR) software.
Dietary intake - proteins11-16 years post CALERIE trialDietary proteins (grams and % of energy intake) will be measured by multiple-pass 24-hour dietary recalls and Nutrition Data System for Research (NDSR) software.
Health-related quality of life11-16 years post CALERIE trialQuality of life as measured by the RAND 36-Item Short Form Survey (SF-36). The RAND SF-36 measures eight aspects of health: physical functioning, role limitations due to physical health problems, role limitations due to personal or emotional problems, energy/fatigue, emotional well-being, social functioning, bodily pain, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. Each item is on a 3- or 5-point Likert scale (1-3 or 1-5). Each response is transformed to a recoded value of 0-100, and the transformed scores of the 9 subscales are averaged to derive a composite score. Higher scores indicate more favorable health states.
Depression status11-16 years post CALERIE trialDepression status as measured by the Beck Depression Inventory II (BDI-II). The 21-item BDI-II measures depression severity. The score range is 0-63, with higher scores indicating greater depression severity. Nineteen items are on a 4-point Likert scale (0-3). Two items are on a 7-point Likert scale, and responses are scaled to 0-3. The values are summed to calculate the total score.
Mood11-16 years post CALERIE trialMood as measured by the Profile of Mood States Second Edition (POMS 2). The POMS 2 assesses six mood subscales using 65 items, each on a 5-point Likert scale (0-4): tension-anxiety (9 items, score range 0-36), depression-dejection (15 items, range 0-60), anger-hostility (12 items, range 0-48), vigor-activity (8 items, range 0-32), fatigue-inertia (7 items, range 0-28), and confusion-bewilderment (7 items, range 0-28). High vigor-activity scores reflect a good mood or emotion, and low scores in the other subscales reflect a good mood or emotion. Total mood disturbance, which is calculated by subtracting the vigor subscale score from the total subscale score (range 0-200), also will be assessed.
Sleep11-16 years post CALERIE trialSleep as measured by the Pittsburgh Sleep Quality Index (PSQI). The PSQI measures sleep quality and disturbance over the course of one month using seven subscales: subjective sleep quality; sleep latency; sleep duration; habitual sleep efficiency; sleep disturbances; use of sleeping medication; and daytime dysfunction. The scoring range of each subscale is 0-3. The scoring range of the Global PSQI (the composite score of the seven subscales) is 0-21. For both the subscales and Global PSQI, higher scores indicate greater difficulties with sleeping.
Sexual function11-16 years post CALERIE trialSexual function as measured by the Derogatis Interview for Sexual Functioning - Self Report (DISF-SR). Both versions of the DISF-SR (male and female) are scored from 20 to 75, with higher scores indicating higher sexual functioning.
Food cravings11-16 years post CALERIE trialFood cravings as measured by the Food Cravings Questionnaire-Trait (FCQ-T). The FCQ-T measures frequency and intensity of food cravings. It has 39 items on a 6-point Likert scale (1-6) and a score range of 39-234. Higher scores indicate more frequent and intense food cravings. Scores on all items are summed for a total score.
Dietary restraint, disinhibition, and hunger11-16 years post CALERIE trialDietary restraint, disinhibition, and hunger as measured by the Three-Factor Eating Questionnaire (TFEQ). The 51-item TFEQ will be used to measure dietary restraint (21 items), disinhibition (16 items), and hunger (14 items). Item responses are scored as 0 or 1 and summed. Higher scores indicate higher levels of restrained eating (range 0-21), disinhibited eating (range 0-16), and predisposition to hunger (range 0-14).
Disordered eating11-16 years post CALERIE trialDisordered eating as measured by the Multiaxial Assessment of Eating Disorder Symptoms (MAEDS). MAEDS will be used to assess six domains of disordered eating: binge eating (range 8-56), restrictive eating (range 9-63), purgative behavior (range 7-49), fear of fatness (range 11-77), avoidance of forbidden foods (range 10-70), and depression (range 11-77).
Body shape perceptions11-16 years post CALERIE trialBody shape perceptions as measured by the Body Shape Questionnaire (BSQ). Items on the BSQ are rated on a 6-point Likert-type scale. The score ranges from 34-204 points. Higher scores indicate increased concern regarding body shape.
Physical activity11-16 years post CALERIE trialPhysical activity as measured by the 7-Day Stanford Physical Activity Recall (PAR). The PAR estimates an individual's time spent in sleep and physical activity for the 7 days prior to the interview. Energy expenditure based on time spent in sleep and physical activities can be estimated. Sub-scores of energy expenditure for each of the following activities are calculated, summed, and averaged to estimate energy expenditure as kilocalories per day: sleep, moderate physical activity, hard physical activity, and very hard physical activity. Higher scores indicate greater physical activity per day. Metabolic equivalent (MET) value for each activity is provided: 1 MET for sleep, 4 METs for moderate activity, 6 METs for hard activity, and 10 METs for very hard activity. Time spent in each activity over 7 days is multiplied by the appropriate MET value. The minimum value for each activity is zero; there is no maximum value.
Resilience11-16 years post CALERIE trialResilience as measured by the 25-item Connor-Davidson Resilience Scale (CD-RISC-25). CD-RISC-25 is scored from 0 to 100, with higher scores indicating higher resilience.
Total cholesterol11-16 years post CALERIE trialTotal cholesterol will be measured in mg/dL using a standard lipid panel.
High-density lipoprotein cholesterol (HDL-C)11-16 years post CALERIE trialHDL-C will be measured in mg/dL using a standard lipid panel.
Triglycerides11-16 years post CALERIE trialTriglycerides will be measured in mg/dL using a standard lipid panel.
Low-density lipoprotein cholesterol (LDL-C)11-16 years post CALERIE trialLDL-C will be calculated in mg/dL using measured values of total cholesterol, HDL-C, and triglycerides.
Glucose - 0 min (OGTT)11-16 years post CALERIE trialGlucose (mg/dL) will be measured at 0 minutes (pre-dose) during an OGTT to evaluate glucoregulatory response.
Glucose - 30 min (OGTT)11-16 years post CALERIE trialGlucose (mg/dL) will be measured at 30 minutes post dose during an OGTT to evaluate glucoregulatory response.
Glucose - 60 min (OGTT)11-16 years post CALERIE trialGlucose (mg/dL) will be measured at 60 minutes post dose during an OGTT to evaluate glucoregulatory response.
Glucose - 90 min (OGTT)11-16 years post CALERIE trialGlucose (mg/dL) will be measured at 90 minutes post dose during an OGTT to evaluate glucoregulatory response.
Glucose - 120 min (OGTT)11-16 years post CALERIE trialGlucose (mg/dL) will be measured at 120 minutes post dose during an OGTT to evaluate glucoregulatory response.
Insulin resistance11-16 years post CALERIE trialInsulin resistance will be calculated using the Homeostatic Model Assessment (HOMA) and measured values of fasting glucose (mmol/L) and fasting insulin (μ/L): (fasting glucose × fasting insulin) ∕ 22.5
Beta-cell function11-16 years post CALERIE trialBeta-cell function will be calculated using HOMA-β and measures of fasting insulin (μ/L) and fasting glucose (mg/dL): HOMA-β (%) = (360 × fasting insulin) ∕ (fasting glucose - 63)
Insulinogenic Index11-16 years post CALERIE trialInsulinogenic index will be calculated as the ratio of change in plasma insulin (I) from 0 to 30 min of the OGTT to the change in plasma glucose (G) over the same period (∆I0-30 min ∕ ∆G0-30 min).
Insulin Sensitivity Index (ISI)11-16 years post CALERIE trialInsulin sensitivity index will be calculated as 1 ∕ fasting insulin (μ/L).
Oral Disposition Index11-16 years post CALERIE trialThe Oral Disposition Index will be calculated as the product of insulinogenic index and insulin sensitivity index.
Triiodothyronine (T3)11-16 years post CALERIE trialT3, a blood-based marker of thyroid function, will be measured in ng/dL.
Thyroxine (T4)11-16 years post CALERIE trialT4, a blood-based marker of thyroid function, will be measured in ng/dL.
Thyroid stimulating hormone (TSH)11-16 years post CALERIE trialTSH, a blood-based marker of thyroid function, will be measured in μIU/mL.
Alkaline phosphatase (ALKP)11-16 years post CALERIE trialALKP, a blood-based marker of liver function, will be measured in IU/L.
Alanine transaminase (ALT)11-16 years post CALERIE trialALT, a blood-based marker of liver function, will be measured in U/L.
Aspartate aminotransferase (AST)11-16 years post CALERIE trialAST, a blood-based marker of liver function, will be measured in U/L.
Albumin11-16 years post CALERIE trialAlbumin, a blood-based marker of liver and kidney function, will be measured in g/dL.
Blood Urea Nitrogen (BUN)11-16 years post CALERIE trialBUN, a blood-based marker of kidney function, will be measured in mg/dL.
Total Proteins11-16 years post CALERIE trialTotal proteins are computed as a sum of albumin and globulin. Total proteins are indicative of blood vessel and immune system function and will be measured in g/dL.
Bilirubin11-16 years post CALERIE trialBilirubin, a blood-based marker of liver function, will be measured in mg/dL.
Creatine Phosphokinase (CPK)11-16 years post CALERIE trialCPK, an enzyme marker of energy homeostasis, will be measured in U/L.
Lactate Dehydrogenase (LDH)11-16 years post CALERIE trialLDH, an enzyme marker of liver function, will be measured in U/L.
Globulin11-16 years post CALERIE trialGlobulin, a blood-based marker of liver function, will be measured in g/dL.
Albumin/Globulin (A/G) ratio11-16 years post CALERIE trialA/G ratio is a blood-based marker used to monitor nutritional status and immune system, kidney, and liver function. This marker is a ratio, and therefore does not have units.
Uric Acid11-16 years post CALERIE trialUric acid, a blood-based marker of purine metabolism, will be measured in mg/dL.
Calcium (Ca)11-16 years post CALERIE trialCalcium, a blood-based mineral, will be measured in mg/dL.
Phosphorus (P)11-16 years post CALERIE trialPhosphorus, a blood-based mineral, will be measured in mg/dL.
Magnesium (Mg)11-16 years post CALERIE trialMagnesium, a blood-based mineral, will be measured in meq/L.
Sodium (Na+)11-16 years post CALERIE trialSodium, an electrolyte that reflects the body's fluid balance, will be measured in meq/L.
Potassium (K+)11-16 years post CALERIE trialPotassium, an electrolyte that reflects the body's fluid balance, will be measured in meq/L.
Chloride (Cl-)11-16 years post CALERIE trialChloride, an electrolyte that reflects the body's fluid balance, will be measured in meq/L.
Apoprotein A111-16 years post CALERIE trialApoprotein A1, a blood-based marker of lipid metabolism, will be measured in mg/dL.
Apoprotein B11-16 years post CALERIE trialApoprotein B, a blood-based marker of lipid metabolism, will be measured in mg/dL.

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORSai Krupa Das, PhD

Tufts University

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jun 10, 2026