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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Aging

Intervention / Treatment
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* Behavioral: Caloric Restriction (CR)
* Behavioral: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caloric Restriction (CR)<br>25% caloric restriction | Behavioral: Caloric Restriction (CR)<br>* Participants follow a diet with 25% fewer calories than calculated at baseline over a period of 24 months<br>|
| Active Comparator: Control, Ad libitum (AL)<br>Ad libitum energy intake | Behavioral: Control<br>* Participants continue their current diet for 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Core Body Temperature, Baseline to 12 Months |  | Baseline to 12 months | 
| Change in Core Temperature, Baseline to 24 Months |  | Baseline to 24 months | 
| Change in Resting Metabolic Rate (RMR) Corrected for Changes in Body Composition, Baseline to 12 Months |  | Baseline, 12 months | 
| Change in Resting Metabolic Rate (RMR) Corrected for Changes in Body Composition |  | Baseline, 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tumor Necrosis Factor-α (TNF-α), Baseline to 12 Months |  | change baseline to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dietary restriction, disease /disorder prevention /control, nutrition of aging, bioenergetics, cardiovascular function, disease /disorder proneness /risk, insulin sensitivity / resistance