Diet and Body Composition (CENTRAL)

Effect of Weight-loss Diet Strategies and Exercise on Dynamics of Body Fat Depots and Metabolic Rate

The investigators hypothesize that differential dynamics in fat depots in response to two opposing dietary strategies mediate the beneficial metabolic effects during weight loss and regain phases.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Weight-loss diet strategy (+) exercise (PA); Other: weight loss (-) exercise (PA)

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Dimona, Israel
    • nuclear research center Negev

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Elevated waist circumference:

  • Men: > 40 inches (102 cm)
  • Women> 35 inches (88 cm)
• Poor dieters with TG>150mg/dL and high-density-lipoprotein cholesterol [HDL-c] <40 mg/dL for men and <50 mg/dL for women

Exclusion Criteria:

• Pregnant or lactating women
• Serum creatinine LT 2 mg/dl
• Disturbed liver function (LT 3 fold level of ALT and AST enzymes)
• Active cancer
• Individuals who cannot start physical activity in the gym
• Individuals that are highly physically active (more than 4 hours/week)
• Active in other nutritional trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low fat diet; Weight-loss diet strategy	Other: Weight-loss diet strategy (+) exercise (PA); Weight-loss diet strategy with a free gym membership; monthly 60-minute educational workshops; 3 sessions of workout per week of mostly aerobic training; Other: weight loss (-) exercise (PA); Weight-loss diet strategy without exercise
Experimental: low carb diet; Weight-loss diet strategy	Other: Weight-loss diet strategy (+) exercise (PA); Weight-loss diet strategy with a free gym membership; monthly 60-minute educational workshops; 3 sessions of workout per week of mostly aerobic training; Other: weight loss (-) exercise (PA); Weight-loss diet strategy without exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
body fat composition	changes in body fat (MRI)	0, 6,18 months
obesity	changes in weight	0, 6, 18 months
abdominal obesity	changes in waist circumference	0, 6, 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid profile	Changes in lipid biomarkers: total cholesterol (mg/dL), triglycerides (mg/dL), HDLc (mg/dL), LDLc (mg/dL) (blood draw)	0, 6, 18 months
Glycemic control	Changes in fasting glucose (mg/dL) (blood draw)	0, 6, 18 months
Glycemic control	Changes in insulin (μIU/mL) (blood draw)	0, 6, 18 months
Inflammatory state	Changes hsCRP (mg/L) (blood draw)	0, 6, 18 months
Metabolomic	Changes in sub-lipids (blood draw)	0, 6, 18 months
Metabolomic	Changes in sub-proteins ( blood draw)	0, 6, 18 months
Liver function (blood biomarkers)	Changes in ALT (U/l), AST (U/l), ALKP (U/I), GGT (U/l) (blood draw)	0, 6, 18 months
Genetic signature	SNPs (variants) associated with fat distribution and visceral fat (blood draw)	baseline
Epigenetics	changes in genes' methylation (blood draw)	0, 6, 18 months
Epigenetics	changes in mRNAs (blood draw)	0, 6, 18 months

Collaborators and Investigators

• Sponsor: Ben-Gurion University of the Negev

Publications and helpful links

General Publications

• Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, Golan R, Fraser D, Bolotin A, Vardi H, Tangi-Rozental O, Zuk-Ramot R, Sarusi B, Brickner D, Schwartz Z, Sheiner E, Marko R, Katorza E, Thiery J, Fiedler GM, Bluher M, Stumvoll M, Stampfer MJ; Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008 Jul 17;359(3):229-41. doi: 10.1056/NEJMoa0708681. Erratum In: N Engl J Med. 2009 Dec 31;361(27):2681.
• Heianza Y, Krohn K, Yaskolka Meir A, Wang X, Ziesche S, Ceglarek U, Bluher M, Keller M, Kovacs P, Shai I, Qi L. Changes in Circulating miR-375-3p and Improvements in Visceral and Hepatic Fat Contents in Response to Lifestyle Interventions: The CENTRAL Trial. Diabetes Care. 2022 Aug 1;45(8):1911-1913. doi: 10.2337/dc21-2517.
• Heianza Y, Krohn K, Xue Q, Yaskolka Meir A, Ziesche S, Ceglarek U, Bluher M, Keller M, Kovacs P, Shai I, Qi L. Changes in circulating microRNAs-99/100 and reductions of visceral and ectopic fat depots in response to lifestyle interventions: the CENTRAL trial. Am J Clin Nutr. 2022 Jul 6;116(1):165-172. doi: 10.1093/ajcn/nqac070.
• Tsaban G, Bilitzky-Kopit A, Yaskolka Meir A, Zelicha H, Gepner Y, Shelef I, Orr O, Chassidim Y, Sarusi B, Ceglarek U, Stumvoll M, Bluher M, Stampfer MJ, Shai I, Schwarzfuchs D. The Effect of Weight-Loss Interventions on Cervical and Chin Subcutaneous Fat Depots; the CENTRAL Randomized Controlled Trial. Nutrients. 2021 Oct 27;13(11):3827. doi: 10.3390/nu13113827.
• Yaskolka Meir A, Keller M, Muller L, Bernhart SH, Tsaban G, Zelicha H, Rinott E, Kaplan A, Gepner Y, Shelef I, Schwarzfuchs D, Ceglarek U, Stadler P, Bluher M, Stumvoll M, Kovacs P, Shai I. Effects of lifestyle interventions on epigenetic signatures of liver fat: Central randomized controlled trial. Liver Int. 2021 Sep;41(9):2101-2111. doi: 10.1111/liv.14916. Epub 2021 May 28.
• Yaskolka Meir A, Keller M, Bernhart SH, Rinott E, Tsaban G, Zelicha H, Kaplan A, Schwarzfuchs D, Shelef I, Gepner Y, Li J, Lin Y, Bluher M, Ceglarek U, Stumvoll M, Stadler PF, Stampfer MJ, Kovacs P, Liang L, Shai I. Lifestyle weight-loss intervention may attenuate methylation aging: the CENTRAL MRI randomized controlled trial. Clin Epigenetics. 2021 Mar 4;13(1):48. doi: 10.1186/s13148-021-01038-0.
• Gepner Y, Goldstein N, Shelef I, Schwarzfuchs D, Zelicha H, Meir AY, Tsaban G, Grossman E. Dissociation Between Long-term Weight Loss Intervention and Blood Pressure: an 18-month Randomized Controlled Trial. J Gen Intern Med. 2021 Aug;36(8):2300-2306. doi: 10.1007/s11606-021-06655-2. Epub 2021 Feb 25.
• Gepner Y, Shelef I, Komy O, Cohen N, Schwarzfuchs D, Bril N, Rein M, Serfaty D, Kenigsbuch S, Zelicha H, Yaskolka Meir A, Tene L, Bilitzky A, Tsaban G, Chassidim Y, Sarusy B, Ceglarek U, Thiery J, Stumvoll M, Bluher M, Stampfer MJ, Rudich A, Shai I. The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol. 2019 Aug;71(2):379-388. doi: 10.1016/j.jhep.2019.04.013. Epub 2019 May 8.
• Tene L, Shelef I, Schwarzfuchs D, Gepner Y, Yaskolka Meir A, Tsaban G, Zelicha H, Bilitzky A, Komy O, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Chassidim Y, Sarusy B, Ceglarek U, Stumvoll M, Bluher M, Thiery J, Stampfer MJ, Rudich A, Shai I. The effect of long-term weight-loss intervention strategies on the dynamics of pancreatic-fat and morphology: An MRI RCT study. Clin Nutr ESPEN. 2018 Apr;24:82-89. doi: 10.1016/j.clnesp.2018.01.008. Epub 2018 Feb 6.
• Gepner Y, Shelef I, Schwarzfuchs D, Cohen N, Bril N, Rein M, Tsaban G, Zelicha H, Yaskolka Meir A, Tene L, Sarusy B, Rosen P, Hoffman JR, Stout JR, Thiery J, Ceglarek U, Stumvoll M, Bluher M, Stampfer MJ, Shai I. Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub-study of the CENTRAL trial. PLoS One. 2017 Nov 30;12(11):e0188431. doi: 10.1371/journal.pone.0188431. eCollection 2017.
• Gepner Y, Shelef I, Schwarzfuchs D, Zelicha H, Tene L, Yaskolka Meir A, Tsaban G, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Komy O, Wolak A, Chassidim Y, Golan R, Avni-Hassid H, Bilitzky A, Sarusi B, Goshen E, Shemesh E, Henkin Y, Stumvoll M, Bluher M, Thiery J, Ceglarek U, Rudich A, Stampfer MJ, Shai I. Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial. Circulation. 2018 Mar 13;137(11):1143-1157. doi: 10.1161/CIRCULATIONAHA.117.030501. Epub 2017 Nov 15.
• Tsaban G, Wolak A, Avni-Hassid H, Gepner Y, Shelef I, Henkin Y, Schwarzfuchs D, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Tene L, Zelicha H, Yaskolka-Meir A, Komy O, Bilitzky A, Chassidim Y, Ceglarek U, Stumvoll M, Bluher M, Thiery J, Dicker D, Rudich A, Stampfer MJ, Shai I. Dynamics of intrapericardial and extrapericardial fat tissues during long-term, dietary-induced, moderate weight loss. Am J Clin Nutr. 2017 Oct;106(4):984-995. doi: 10.3945/ajcn.117.157115. Epub 2017 Aug 16.
• Zelicha H, Schwarzfuchs D, Shelef I, Gepner Y, Tsaban G, Tene L, Yaskolka Meir A, Bilitzky A, Komy O, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Chassidim Y, Sarusi B, Thiery J, Ceglarek U, Stumvoll M, Bluher M, Haviv YS, Stampfer MJ, Rudich A, Shai I. Changes of renal sinus fat and renal parenchymal fat during an 18-month randomized weight loss trial. Clin Nutr. 2018 Aug;37(4):1145-1153. doi: 10.1016/j.clnu.2017.04.007. Epub 2017 May 2.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: February 8, 2012
• First Submitted That Met QC Criteria: February 9, 2012
• First Posted (Estimate): February 10, 2012

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: October 21, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: abdominal obesity
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: ISF256/09; 256/09 (Other Grant/Funding Number: ISF256/09)