Hormonal Regulation of Body Weight Maintenance

The investigators here propose to perform a collaborative clinical research effort including a randomized controlled trial investigating the mechanisms of weight maintenance and their relation to a lifestyle intervention in children, adolescents and adults. The detailed investigation and analysis of the variability and dynamics of the endocrine circuits responding to a negative energy balance and weight loss will be accompanied and enhanced by specific clinical projects targeting peripheral and central-nervous aspects of hormonal counter-regulation after weight loss. Mechanisms of endocrine counter-regulation and potential therapeutic approaches will be studied.

Study Overview

• Status: Completed
• Conditions: Obesity; Insulin Resistance; Weight Loss; Weight Gain; Hormone Disturbance; Skeletal Muscle; Adipose Tissue
• Intervention / Treatment: Behavioral: placebo; Behavioral: multimodal lifestyle intervention

• Study Type: Interventional
• Enrollment (Actual): 286
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12200
    • Charité

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI > 27 kg/m2 (adults)

Exclusion Criteria:

• weight loss of more than 5kg in the last 2 months
• pregnancy, breastfeeding

• patients with:

  • severe heart failure
  • impaired hepatic or renal function
  • anaemia
  • disturbed coagulation (biopsies will not be taken in those subjects)
  • infection, malabsorption
  • severe hypertension
  • cancer within the last 5 years
  • eating disorders or any other psychiatric condition that would interact with the trial intervention
  • any other endocrine disorder
• changes of smoking habits or diets within the last 3 months prior to study inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; Placebo	Behavioral: placebo; no intervention, only follow up
Experimental: lifestyle intervention; After an initial weight loss, the weight regain will be measured during multimodal lifestyle intervention in children, adolescents and adults	Behavioral: multimodal lifestyle intervention; After an initial weight loss, the weight regain will be measured during multimodal lifestyle intervention in children, adolescents and adults

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI will be assessed during lifestyle intervention in (1) children and adolescents and (2) adults vs. placebo	BMI (kg/m2) will be analyzed after intentional weight loss in two comparable parts of a randomized controlled trial including (1) children and adolescents and (2) adults. Therefore effects of a multimodal lifestyle intervention will be compared to placebo.	21 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of leptin during lifestyle intervention	Measurement of leptin at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up	month -3, month 0, month 12, month 18
Evaluation of leptin during follow up	Measurement of leptin during follow up until the 48 months	48 months
Evaluation of catecholamines during follow up	Measurement of catecholamines during follow up until the 48 months	48 months
Evaluation of catecholamines during lifestyle intervention	Measurement of catecholamines at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up	month -3, month 0, month 12, month 18
Evaluation of cortisol during lifestyle intervention	Measurement of cortisol at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up	month -3, month 0, month 12, month 18
Evaluation of cortisol during follow up	Measurement of cortisol during follow up until the 48 months	48 months
Evaluation of glucagon-like peptide 1 (GLP1) during lifestyle intervention	Measurement of GLP1 at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up	month -3, month 0, month 12, month 18
Evaluation of GLP1 during follow up	Measurement of GLP1 during follow up until the 48 months	48 months
Evaluation of glucose-dependent insulinotropic polypeptide (GIP) during lifestyle intervention	Measurement of GIP at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up	month -3, month 0, month 12, month 18
Evaluation of GIP during follow up	Measurement of GIP during follow up until the 48 months	48 months
Evaluation of thyroid hormones during lifestyle intervention	Measurement of thyroid hormones at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up	month -3, month 0, month 12, month 18
Evaluation of thyroid hormones during follow up	Measurement of thyroid hormones during follow up until the 48 months	48 months
Evaluation of insulin during lifestyle intervention	Measurement of insulin at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up	month -3, month 0, month 12, month 18
Evaluation of insulin during follow up	Measurement of insulin during follow up until the 48 months	48 months
Evaluation of insulin-like growth factor 1 (IGF1) during lifestyle intervention	Measurement of IGF1 at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up	month -3, month 0, month 12, month 18
Evaluation of IGF1 during follow up	Measurement of IGF1 during follow up until the 48 months	48 months
Evaluation of natriuretic peptide during lifestyle intervention	Measurement of natriuretic peptide at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and after additional 6 months follow up	month -3, month 0, month 12, month 18
Evaluation of natriuretic peptide during follow up	Measurement of natriuretic peptide during follow up until the 48 months	48 months
Evaluation of blood pressure during lifestyle intervention	Measurement of blood pressure at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up	month -3, month 0, month 12, month 18, month 24, month 36, month 48
Evaluation of free fatty acids (FFAs) during lifestyle intervention	Measurement of FFAs at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up	month -3, month 0, month 12, month 18, month 24, month 36, month 48
Evaluation of respiratory coefficient during lifestyle intervention	Measurement of respiratory coefficient at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up	month -3, month 0, month 12, month 18, month 24, month 36, month 48
Measurement of messenger ribonucleic acid (mRNA) changes in adipose and skeletal muscle before (T-3), after weight loss (T0) and after as well as after 12 months randomized lifestyle intervention (or placebo)	Measurement of systemic and tissue specific changes in adipose tissue and skeletal muscle using RNA sequencing (counts)	month -3, month 0, month 12
Measurement of insulin sensitivity	Measurement of systemic and tissue specific changes in adipose and muscle insulin sensitivity using hyperinsulinemic clamp (mg•kg-1•min-1/(mU•L-1)) before (T-3), after weight loss (T0) and after as well as after 12 months randomized lifestyle intervention (or placebo)	month -3, month 0, month 12
Prediction of body weight regain	No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on long-term course of BMI (18 and 48 months) using mathematical models	month 18, month 48
Prediction of insulin sensitivity	No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on insulin sensitivity (18 and 48 months) using mathematical models	month 18, month 48
Prediction of energy expenditure	No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on energy expenditure (18 and 48 months) using mathematical models	month 18, month 48
Prediction of muscle mass	No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on muscle mass (18 and 48 months) using mathematical models	month 18, month 48
Prediction of fat mass	No additional measurement will be done. However, we will analyse the predictive impact of already measured parameters on fat mass (18 and 48 months) using mathematical models	month 18, month 48
BMI course after a lifestyle intervention in (1) children and adolescents and (2) adults vs. placebo	BMI (kg/m2) after the randomized control trial (RCT) (18 months) will be analyzed up to 48 months.	month 24, month 36, month 48
changes of fatty acids during the intervention	Analysis of fatty acids at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up	month -3, month 0, month 12, month 18, month 24, month 36, month 48
changes acylcarnitines	Analysis of acylcarnitines at baseline and after 3 months of weight loss	month -3, month 0
changes acylcarnitines	Analysis of acylcarnitines after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up	month 12, month 18, month 24, month 36, month 48
body composition	Whole body fat mass (kg, %) will be measured at baseline, after 3 months of weight loss, as well as after 12 months randomized lifestyle intervention (or placebo) and and after additional 36 months follow up	month -3, month 0, month 12, month 18, month 24, month 36, month 48

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: German Research Foundation

Publications and helpful links

General Publications

• Li L, Soll D, Leupelt V, Spranger J, Mai K. Weight loss-induced improvement of body weight and insulin sensitivity is not amplified by a subsequent 12-month weight maintenance intervention but is predicted by adaption of adipose atrial natriuretic peptide system: 48-month results of a randomized controlled trial. BMC Med. 2022 Jul 28;20(1):238. doi: 10.1186/s12916-022-02435-9.
• Soll D, Gawron J, Pletsch-Borba L, Spranger J, Mai K. Long-term impact of the metabolic status on weight loss-induced health benefits. Nutr Metab (Lond). 2022 Mar 28;19(1):25. doi: 10.1186/s12986-022-00660-w.
• Li L, Spranger L, Stobaus N, Beer F, Decker AM, Wernicke C, Brachs S, Brachs M, Spranger J, Mai K. Fetuin-B, a potential link of liver-adipose tissue cross talk during diet-induced weight loss-weight maintenance. Nutr Diabetes. 2021 Oct 5;11(1):31. doi: 10.1038/s41387-021-00174-z.
• Li L, Spranger L, Soll D, Beer F, Brachs M, Spranger J, Mai K. Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections? Metabolism. 2020 Dec;113:154401. doi: 10.1016/j.metabol.2020.154401. Epub 2020 Oct 13.
• Brachs S, Polack J, Brachs M, Jahn-Hofmann K, Elvert R, Pfenninger A, Barenz F, Margerie D, Mai K, Spranger J, Kannt A. Genetic Nicotinamide N-Methyltransferase (Nnmt) Deficiency in Male Mice Improves Insulin Sensitivity in Diet-Induced Obesity but Does Not Affect Glucose Tolerance. Diabetes. 2019 Mar;68(3):527-542. doi: 10.2337/db18-0780. Epub 2018 Dec 14.
• Mai K, Li L, Wiegand S, Brachs M, Leupelt V, Ernert A, Kuhnen P, Hubner N, Robinson P, Chen W, Krude H, Spranger J. An Integrated Understanding of the Molecular Mechanisms of How Adipose Tissue Metabolism Affects Long-term Body Weight Maintenance. Diabetes. 2019 Jan;68(1):57-65. doi: 10.2337/db18-0440. Epub 2018 Nov 2.
• Bau AM, Ernert A, Krude H, Wiegand S. Hormonal regulatory mechanisms in obese children and adolescents after previous weight reduction with a lifestyle intervention: maintain - paediatric part - a RCT from 2009-15. BMC Obes. 2016 Jun 10;3:29. doi: 10.1186/s40608-016-0110-8. eCollection 2016.
• Brachs M, Wiegand S, Leupelt V, Ernert A, Kintscher U, Jumpertz von Schwarzenberg R, Decker AM, Bobbert T, Hubner N, Chen W, Krude H, Spranger J, Mai K. ANP system activity predicts variability of fat mass reduction and insulin sensitivity during weight loss. Metabolism. 2016 Jun;65(6):935-43. doi: 10.1016/j.metabol.2016.03.013. Epub 2016 Apr 7.
• Weygandt M, Mai K, Dommes E, Ritter K, Leupelt V, Spranger J, Haynes JD. Impulse control in the dorsolateral prefrontal cortex counteracts post-diet weight regain in obesity. Neuroimage. 2015 Apr 1;109:318-27. doi: 10.1016/j.neuroimage.2014.12.073. Epub 2015 Jan 7.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2010
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: February 17, 2009
• First Submitted That Met QC Criteria: February 24, 2009
• First Posted (Estimate): February 25, 2009

Study Record Updates

• Last Update Posted (Actual): January 17, 2018
• Last Update Submitted That Met QC Criteria: January 12, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: weight regain; endocrine counterregulation
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Body Weight Changes; Weight Loss; Insulin Resistance; Body Weight; Weight Gain; Endocrine System Diseases
• Other Study ID Numbers: EA2/017/09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO