CALERIE Phase II Ancillary: Metabolic — CALERIE-II  

Aging Clinical Trial

Official title: CALERIE Phase II Ancillary 2: Metabolic Adaptation After Two Years of Caloric Restriction in Non Obese Humans

Status Completed

Clinical Trial Summary

The primary aim of this NIA sponsored ancillary study of phase 2 CALERIE is to measure whether metabolic adaptation lasts up to 2 years in response to a 25% calorie restriction in normal-weight and slightly overweight individuals. Energy metabolism (24-hour sedentary and sleeping) will be measured in a respiratory chamber. Other measures include the activities of the sympathetic nervous and thyroid axes, oxidative stress in lipids, protein and DNA, organ size by MRI and echocardiography, and posture allocation (time spent engaging in different activities and the energy expended during these activities), and activity temperament (the innate predilection for movement). This set of studies will allow assessment of whether the previously observed metabolic adaptation in response to 25% caloric restriction is long lasting (up to two years), associated with reduced thyroid and sympathetic activities and reduced oxidative damage. The studies of organ sizes (liver, spleen, kidney, heart, adipose and muscle) by MRI and echo (heart) is essential to determine whether the metabolic adaptation is related to decreased organ sizes or improved organ energy metabolism efficiency. The above described measures will be performed at baseline and after 1 and 2 years of a 25% caloric restriction in 50 non-obese humans and in 25 sex-, BMI- and age- matched subjects who will not engage in caloric restriction.

Clinical Trial Description

Hypothesis 1: The decrease in energy expenditure (sedentary and sleeping) will be larger than that expected on the basis of loss of fat-free mass and fat mass even after weight stabilization. Aim 1: Determine the metabolic adaptation after 1 and 2 years of a 25% CR

Hypothesis 2: The metabolic adaptation (what is not accounted by a decrease in FM and FFM) is not entirely accounted by reduced organ/tissue size (liver, spleen, kidney, heart and brain) but is accompanied by reduced activities of the sympathetic and thyroid systems. Aim 2: Assess the contribution of organ sizes and activities of the thyroid and sympathetic systems to the metabolic adaptation. Results will be compared to in vivo and in vitro oxidative phosphorylation (Smith, PI).

Hypothesis 3: A decrease in markers of oxidative stress to lipid (urinary isoprostanes) DNA (strand breaks) in blood and protein (carbonylation and thiol oxidation) in blood and skeletal muscle tissue after 1 and 2 years of CR will be observed. Aim 3: Determine the changes in oxidative stress after 1 and 2 years of 25% CR by measuring urinary isoprostanes, serum carbonyls, DNA damage in nucleated blood cells and protein oxidation (carbonyls and oxidation of cysteine residues) in skeletal muscle. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Aging

• NCT number: NCT02695511
• Study type: Interventional
• Source: Pennington Biomedical Research Center
• Status: Completed
• Phase: Phase 2
• Start date: May 2007
• Completion date: February 2010