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AgingNCT00427193

CALERIE: Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy

A study testing Caloric Restriction (CR) in people with Aging, run by Duke University at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to test the hypothesis that two years of sustained 25% caloric restriction (CR) in men age 21-50 (inclusive) and women age 21-47 (inclusive) will slow aging and protect against age-related disease processes. Read more about this study

Who is it for?
Ages 21 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Aging
What is being tested?
Caloric Restriction (CR)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
238 participants
Where
3 sitesUnited States
Study dates
May 2007to Nov 2012
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Age must be between 21-50 (inclusive) for men and 21-47 (inclusive) for women
  • Body mass index (BMI) must be greater than or equal to 22 and less than 28
  • Female participants must use acceptable forms of contraception (barrier method, oral contraceptive, intra-uterine device, or similar) and be willing to continue using such a method while enrolled in the study

Who cannot join

  • History or clinical manifestation of cardiovascular disease or an elevated blood pressure (greater than 140/90 mm Hg)
  • Abnormal resting ECG
  • History or clinical manifestation of diabetes
  • History or clinical manifestation of cholelithiasis (the presence or formation of gallstones in the gallbladder or bile ducts)
  • History of anaphylaxis, severe allergies, or asthma
  • History or clinical manifestation of any other significant metabolic, hematologic, pulmonary, cardiovascular, gastrointestinal, neurologic, immune, hepatic, renal, urologic disorders, or cancer that, in opinion of the investigator, would make the candidate ineligible for the study
Show all 29Show fewer
  • History of stomach or intestinal surgery (except appendectomy) or major abdominal, thoracic or non-peripheral vascular surgery within one year prior to the randomization date
  • Any disease or condition that seriously affects body weight and/or body composition
  • Potassium level above the upper limit of normal at the screening visit confirmed by a test repeated within two weeks
  • Hemoglobin, hematocrit, RBC, or iron level below the lower limit of normal at the screening visit confirmed by a test repeated within two weeks
  • Evidence of active liver disease or ALT levels above 1.5 times the upper limit of normal
  • Practice a vegan dietary lifestyle
  • History or clinical manifestation of any eating disorder
  • Any history of pharmacologic treatment for a psychiatric disorder within one year prior to the randomization date or a history of more than one episode of a pharmacologic treatment for a psychiatric disorder within lifetime
  • History of drug or alcohol abuse (up to 14 drinks a week are allowed) within the past two years
  • BDI (Beck Depression Inventory) score of 20 or higher at screening or baseline
  • Treatment with steroids for more than a month within five years prior to the randomization date, or short-term (less than a month) treatment with steroids within six months prior to the randomization date
  • Regular use of other medications, except contraceptives
  • Participated in the CALERIE Phase 1 studies
  • Lost or gained 3 kg or more over the past six months
  • A volunteer must be either a never-smoker of tobacco products or an ex-smoker who quit completely at least 12 months prior to the screening visit
  • Donated blood within 30 days prior to the randomization date
  • Concurrent participation in any other interventional study
  • Breast-feeding or pregnant women or women intending to become pregnant before the scheduled end of the intervention
  • Engaged in a regular program of physical fitness involving some kind of heavy physical activity (e.g., jogging, running or riding fast on a bicycle for 30 minutes or more) five or more times per week over the past year
  • Unwilling to be assigned at random to the CR or control intervention
  • Unwilling or unable to adhere to the rigors of the CR intervention over the entire two-year intervention period
  • Unable or unwilling to discontinue dietary supplements or adhere to the alcohol consumption restrictions during the study
  • Unwilling or unable to adhere to the rigors of the data collection and clinical evaluation schedule over the entire two-year period follow-up period

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Pennington Biomedical Research Center

    Baton Rouge, Louisiana, 70808

  • Jean Mayer Human Nutrition Research Center on Aging at Tufts University

    Boston, Massachusetts, 02111

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE)

The purpose of this study is to test the hypothesis that two years of sustained 25% caloric restriction (CR) in men age 21-50 (inclusive) and women age 21-47 (inclusive) will slow aging and protect against age-related disease processes.

Read the detailed description

The overall aim of CALERIE Phase 2 is to test the hypothesis that two years of sustained caloric restriction (CR), involving a reduction in energy intake to 75% of baseline (25% CR), in healthy, non-obese men aged 21-50 (inclusive) and women aged 21-47 (inclusive), will result in the same adaptive changes that were observed in a wide variety of animal studies. Particular emphasis is on the adaptive responses thought to be involved in slowing the aging process and protecting against age-related disease processes. Primary outcomes include core body temperature and resting metabolic rate. Secondary outcomes include risk factors for cardiovascular disease, inflammatory markers, immune function, psychological and physical function; oxidative changes in lipids, proteins, and DNA; and, risk factors for age-related conditions such as diabetes and body composition. An important secondary aim is to identify potential adverse effects of CR in humans.

The study will be conducted as a multi-center, parallel-group, randomized, controlled trial (RCT). A sample of 200 participants will be enrolled, and assigned to either the CR intervention or a control group. Control participants will be advised to simply continue their current diets. Participants in both treatment arms will be followed over a period of 24 months. A comprehensive set of evaluations will be performed prior to initiating the intervention, with follow-up evaluations at 1, 3, 6, 9, 12, 18 and 24 months afterwards.

Conditions
Aging
Being tested
Caloric Restriction (CR), Control
Keywords
dietary restriction, disease /disorder prevention /control, nutrition of aging, bioenergetics, cardiovascular function, disease /disorder proneness /risk, insulin sensitivity / resistance
Medical subject headings
Disease Susceptibility, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Caloric Restriction (CR)Behavioural

    Participants follow a diet with 25% fewer calories than calculated at baseline over a period of 24 months

  • ControlBehavioural

    Participants continue their current diet for 24 months

Study groups in NCT00427193
Study groupRoleWhat they receive
Caloric Restriction (CR)Experimental25% caloric restriction
Receives: Behavioral: Caloric Restriction (CR)
Control, Ad libitum (AL)Active comparatorAd libitum energy intake
Receives: Behavioral: Control

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Core Body Temperature, Baseline to 12 Months

    Measured: Baseline to 12 months

  2. Change in Core Temperature, Baseline to 24 Months

    Measured: Baseline to 24 months

  3. Change in Resting Metabolic Rate (RMR) Corrected for Changes in Body Composition, Baseline to 12 Months

    Measured: Baseline, 12 months

  4. Change in Resting Metabolic Rate (RMR) Corrected for Changes in Body Composition

    Measured: Baseline, 24 months

Secondary outcomes (1)
  1. Change in Tumor Necrosis Factor-α (TNF-α), Baseline to 12 Months

    Measured: change baseline to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2007 (estimated)
  2. Study startMay 2007
  3. Primary completionNov 2012
  4. Study completionNov 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
238 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00427193
Sponsor's protocol ID
Pro00016876
Other IDs
PBRC U01-AG0204878, Tufts U01-AG020480, WashU U01-AG020487, DCRI/Duke U01-AG022132, AG0078
Status last verified
Mar 2022
First submitted
24 Jan 2007
Last updated
16 Mar 2022
Data monitoring committee
Yes

Publications

  • Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, Roberts SB; CALERIE Study Group. A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. J Gerontol A Biol Sci Med Sci. 2015 Sep;70(9):1097-104. doi: 10.1093/gerona/glv057. Epub 2015 Jul 17.

    PubMed 26187233
  • Rochon J, Bales CW, Ravussin E, Redman LM, Holloszy JO, Racette SB, Roberts SB, Das SK, Romashkan S, Galan KM, Hadley EC, Kraus WE; CALERIE Study Group. Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy. J Gerontol A Biol Sci Med Sci. 2011 Jan;66(1):97-108. doi: 10.1093/gerona/glq168. Epub 2010 Oct 5.

    PubMed 20923909
  • Racette SB, Rochon J, Uhrich ML, Villareal DT, DAS SK, Fontana L, Bhapkar M, Martin CK, Redman LM, Fuss PJ, Roberts SB, Kraus WE. Effects of Two Years of Calorie Restriction on Aerobic Capacity and Muscle Strength. Med Sci Sports Exerc. 2017 Nov;49(11):2240-2249. doi: 10.1249/MSS.0000000000001353.

    PubMed 29045325
  • Belsky DW, Huffman KM, Pieper CF, Shalev I, Kraus WE. Change in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis. J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):4-10. doi: 10.1093/gerona/glx096.

    PubMed 28531269
  • Martin CK, Bhapkar M, Pittas AG, Pieper CF, Das SK, Williamson DA, Scott T, Redman LM, Stein R, Gilhooly CH, Stewart T, Robinson L, Roberts SB; Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) Phase 2 Study Group. Effect of Calorie Restriction on Mood, Quality of Life, Sleep, and Sexual Function in Healthy Nonobese Adults: The CALERIE 2 Randomized Clinical Trial. JAMA Intern Med. 2016 Jun 1;176(6):743-52. doi: 10.1001/jamainternmed.2016.1189.

    PubMed 27136347
  • Warmbrunn MV, Biswas RK, Don AS, Lastra Cagigas M, Li Y, Yang L, Twigg SM, Fiorito G, Fontana L. Caloric restriction improves glycemic control via the adiponectin-ceramide axis in non-obese men and women: the CALERIE 2 randomized controlled trial. Nat Commun. 2026 Jul 9;17(1):8507. doi: 10.1038/s41467-026-74468-0.

    PubMed 42425963
  • Jovanovic B, Singh S, Zhang F, Williams EA, Roberts SB, Lowe MR. Prospective Association Between Weight Variability and Subsequent Long-Term Weight Loss in the CALERIE Study. Obesity (Silver Spring). 2026 Jul;34(7):1409-1419. doi: 10.1002/oby.70235. Epub 2026 Jun 18.

    PubMed 42316515
  • Li Y, Xu X, Sehgal R, He X, Zheng Y, Chen X, Xu K. Effect of caloric restriction on organ-specific biological aging in a randomized clinical trial. Clin Nutr. 2026 May;60:106625. doi: 10.1016/j.clnu.2026.106625. Epub 2026 Mar 14.

    PubMed 41895150
  • Dugan C, Das SK, Racette SB, Martin CK, Ravussin E, Redman LM, Hennigar SR. Effect of 2-Year Caloric Restriction in the Absence of Malnutrition on Indicators of Anemia, Iron Status, and Hepcidin in Healthy Adults: A Randomized Clinical Trial. J Nutr. 2026 May;156(5):101474. doi: 10.1016/j.tjnut.2026.101474. Epub 2026 Mar 11.

    PubMed 41825741
  • Stinson EJ, Collins E, Cabeza De Baca T, Gluck ME, Dote-Montero M, Racette SB, Kavouras SA, Das SK, Piaggi P, Votruba S, Hale A, Chang DC. Use of Machine Learning to Identify Determinants of Habitual-Preformed Water Intake. J Nutr. 2026 May;156(5):101475. doi: 10.1016/j.tjnut.2026.101475. Epub 2026 Mar 11.

    PubMed 41825738
  • Racette SB, Silver RE, Barry VG, DeGraff JJ, Gunning JA, Kebbe M, Gilhooly CH, Das SK. Diet quality and nutritional adequacy during a 2-year calorie restriction intervention: the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy 2 trial. Am J Clin Nutr. 2026 Mar;123(3):101182. doi: 10.1016/j.ajcnut.2025.101182. Epub 2025 Dec 29.

    PubMed 41475553
  • Dorling JL, Martin CK, Das SK, Racette SB, Redman LM, Huffman KM, Hochsmann C, Kraus WE. Association between physical activity energy expenditure and markers of healthspan during prolonged calorie restriction in individuals without obesity: observations from the CALERIE phase 2 randomized controlled trial. Int J Behav Nutr Phys Act. 2025 Oct 7;22(1):124. doi: 10.1186/s12966-025-01825-5.

    PubMed 41057847
  • Ryan CP, Corcoran DL, Banskota N, Eckstein Indik C, Floratos A, Friedman R, Kobor MS, Kraus VB, Kraus WE, MacIsaac JL, Orenduff MC, Pieper CF, White JP, Ferrucci L, Horvath S, Huffman KM, Belsky DW. The CALERIE Genomic Data Resource. Nat Aging. 2025 Feb;5(2):320-331. doi: 10.1038/s43587-024-00775-0. Epub 2024 Dec 13.

    PubMed 39672986
  • Glasbrenner C, Hochsmann C, Pieper CF, Wasserfurth P, Dorling JL, Martin CK, Redman LM, Koehler K. Prediction of individual weight loss using supervised learning: findings from the CALERIETM 2 study. Am J Clin Nutr. 2024 Nov;120(5):1233-1244. doi: 10.1016/j.ajcnut.2024.09.003. Epub 2024 Sep 11.

    PubMed 39270937
  • Ryu S, Spadaro O, Sidorov S, Lee AH, Caprio S, Morrison C, Smith SR, Ravussin E, Shchukina I, Artyomov MN, Youm YH, Dixit VD. Reduction of SPARC protects mice against NLRP3 inflammasome activation and obesity. J Clin Invest. 2023 Oct 2;133(19):e169173. doi: 10.1172/JCI169173.

    PubMed 37781916

Questions about this trial

What is this clinical trial studying?

A study testing Caloric Restriction (CR) in people with Aging, run by Duke University at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Core Body Temperature, Baseline to 12 Months (time frame: Baseline to 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00427193, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2022.

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