Adipose Tissue, Hormone Disturbance, Insulin Resistance, Obesity, Skeletal Muscle, Weight Gain, Weight Loss
Conditions
Keywords
weight regain, endocrine counterregulation
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.
Interventions
BEHAVIORALmultimodal lifestyle intervention
After an initial weight loss, the weight regain will be measured during multimodal lifestyle intervention in children, adolescents and adults
BEHAVIORALplacebo
no intervention, only follow up
Sponsors
German Research Foundation
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 90 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BMI will be assessed during lifestyle intervention in (1) children and adolescents and (2) adults vs. placebo | 21 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of leptin during lifestyle intervention | month -3, month 0, month 12, month 18 | 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 |
| Evaluation of leptin during follow up | 48 months | Measurement of leptin during follow up until the 48 months |
| Evaluation of catecholamines during follow up | 48 months | Measurement of catecholamines during follow up until the 48 months |
| Evaluation of catecholamines during lifestyle intervention | month -3, month 0, month 12, month 18 | 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 |
| Evaluation of cortisol during lifestyle intervention | month -3, month 0, month 12, month 18 | 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 |
| Evaluation of cortisol during follow up | 48 months | Measurement of cortisol during follow up until the 48 months |
| Evaluation of glucagon-like peptide 1 (GLP1) during lifestyle intervention | month -3, month 0, month 12, month 18 | 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 |
| Evaluation of GLP1 during follow up | 48 months | Measurement of GLP1 during follow up until the 48 months |
| Evaluation of glucose-dependent insulinotropic polypeptide (GIP) during lifestyle intervention | month -3, month 0, month 12, month 18 | 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 |
| Evaluation of GIP during follow up | 48 months | Measurement of GIP during follow up until the 48 months |
| Evaluation of thyroid hormones during lifestyle intervention | month -3, month 0, month 12, month 18 | 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 |
| Evaluation of thyroid hormones during follow up | 48 months | Measurement of thyroid hormones during follow up until the 48 months |
| Evaluation of insulin during lifestyle intervention | month -3, month 0, month 12, month 18 | 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 |
| Evaluation of insulin during follow up | 48 months | Measurement of insulin during follow up until the 48 months |
| Evaluation of insulin-like growth factor 1 (IGF1) during lifestyle intervention | month -3, month 0, month 12, month 18 | 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 |
| BMI course after a lifestyle intervention in (1) children and adolescents and (2) adults vs. placebo | month 24, month 36, month 48 | BMI (kg/m2) after the randomized control trial (RCT) (18 months) will be analyzed up to 48 months. |
| Evaluation of natriuretic peptide during lifestyle intervention | month -3, month 0, month 12, month 18 | 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 |
| Evaluation of natriuretic peptide during follow up | 48 months | Measurement of natriuretic peptide during follow up until the 48 months |
| Evaluation of blood pressure during lifestyle intervention | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 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 |
| Evaluation of free fatty acids (FFAs) during lifestyle intervention | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 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 |
| Evaluation of respiratory coefficient during lifestyle intervention | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 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 |
| 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) | month -3, month 0, month 12 | Measurement of systemic and tissue specific changes in adipose tissue and skeletal muscle using RNA sequencing (counts) |
| Measurement of insulin sensitivity | month -3, month 0, month 12 | 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) |
| Prediction of body weight regain | month 18, month 48 | 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 |
| Prediction of insulin sensitivity | month 18, month 48 | 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 |
| Prediction of energy expenditure | month 18, month 48 | 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 |
| Prediction of muscle mass | month 18, month 48 | 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 |
| Prediction of fat mass | month 18, month 48 | 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 |
| changes of fatty acids during the intervention | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 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 |
| changes acylcarnitines | month -3, month 0 | Analysis of acylcarnitines at baseline and after 3 months of weight loss |
| body composition | month -3, month 0, month 12, month 18, month 24, month 36, month 48 | 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 |
| Evaluation of IGF1 during follow up | 48 months | Measurement of IGF1 during follow up until the 48 months |
Countries
Germany
Outcome results
None listed