Clinical trial NCT00850629: Hormonal Regulation of Body Weight Maintenance
Official title: Hormonal Regulation of Body Weight Maintenance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Weight Loss
Weight Gain
Hormone Disturbance
Adipose Tissue
Insulin Resistance
Skeletal Muscle
Keywords: weight regain
endocrine counterregulation
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2009-02-25
Enrollment: 286
Sex: ALL
Minimum age (years): 10
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: BMI will be assessed during lifestyle intervention in (1) children and adolescents and (2) adults vs. placebo
timeFrame: 21 months
Secondary outcomes:
measure: Evaluation of leptin during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18
measure: Evaluation of leptin during follow up
timeFrame: 48 months
measure: Evaluation of catecholamines during follow up
timeFrame: 48 months
measure: Evaluation of catecholamines during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18
measure: Evaluation of cortisol during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18
measure: Evaluation of cortisol during follow up
timeFrame: 48 months
measure: Evaluation of glucagon-like peptide 1 (GLP1) during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18
measure: Evaluation of GLP1 during follow up
timeFrame: 48 months
measure: Evaluation of glucose-dependent insulinotropic polypeptide (GIP) during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18
measure: Evaluation of GIP during follow up
timeFrame: 48 months
measure: Evaluation of thyroid hormones during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18
measure: Evaluation of thyroid hormones during follow up
timeFrame: 48 months
measure: Evaluation of insulin during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18
measure: Evaluation of insulin during follow up
timeFrame: 48 months
measure: Evaluation of insulin-like growth factor 1 (IGF1) during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18
measure: Evaluation of IGF1 during follow up
timeFrame: 48 months
measure: Evaluation of natriuretic peptide during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18
measure: Evaluation of natriuretic peptide during follow up
timeFrame: 48 months
measure: Evaluation of blood pressure during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18, month 24, month 36, month 48
measure: Evaluation of free fatty acids (FFAs) during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18, month 24, month 36, month 48
measure: Evaluation of respiratory coefficient during lifestyle intervention
timeFrame: month -3, month 0, month 12, month 18, month 24, month 36, month 48
measure: 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)
timeFrame: month -3, month 0, month 12
measure: Measurement of insulin sensitivity
timeFrame: month -3, month 0, month 12
measure: Prediction of body weight regain
timeFrame: month 18, month 48
measure: Prediction of insulin sensitivity
timeFrame: month 18, month 48
measure: Prediction of energy expenditure
timeFrame: month 18, month 48
measure: Prediction of muscle mass
timeFrame: month 18, month 48
measure: Prediction of fat mass
timeFrame: month 18, month 48
measure: BMI course after a lifestyle intervention in (1) children and adolescents and (2) adults vs. placebo
timeFrame: month 24, month 36, month 48
measure: changes of fatty acids during the intervention
timeFrame: month -3, month 0, month 12, month 18, month 24, month 36, month 48
measure: changes acylcarnitines
timeFrame: month -3, month 0
measure: changes acylcarnitines
timeFrame: month 12, month 18, month 24, month 36, month 48
measure: body composition
timeFrame: month -3, month 0, month 12, month 18, month 24, month 36, month 48
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite
Study officials:
affiliation: Charite
name: Knut Mai, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.