Randomized Clinical Trial; Medical vs Bariatric Surgery for Adolescents (13-16 y) With Severe Obesity

Study Overview
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Brief Summary
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Severe childhood obesity is associated with both immediate and chronic health problems and a severe impact on psychosocial development. Medical and behavioural interventions rarely result in the significant, durable weight loss necessary to improve health outcomes. This is a randomised clinical trial where 50 adolescents, 13-16 years of age, will be randomised to either early bariatric surgery (Roux-en-Y gastric bypass) or intense conservative treatment and possibly surgery after two years of non-surgical treatment or as they have become 18 years.

Detailed Description
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A multicentre randomised clinical trial where three tertiary referral hospitals recruit patients. Patients and their parents receive information about the study at their paediatric clinic and at the trial web page (www.amos2.se). Standardised procedure, including signed informed consent. Interventions At the end of day of baseline examination patients are randomised to either of two arms: Bariatric surgery with regular follow up Optimised conservative treatment starting with an 8-week Low Calorie Diet period followed by tailored support and treatment by the multidisciplinary team with an intensity of at least one visits a month over at least 2 years Patients in the conservative arm will be reassessed regarding interest of undergoing bariatric surgery two years after inclusion. Sample Size A sample size of 50 (25+25) leaves a power of more than 95% to evaluate a possible superiority of >10% weight difference between the two groups, assuming a 15% standard deviation in weight loss over follow-up at 2.5% significance level. This number also allows assessment for differences in cardiovascular risk factors with sufficient power and acceptable power for demonstrating differences in quality of life and cognitive functions. 3.6 Randomization The computerized random allocation is performed during the day of baseline examination and patients were informed of their assignment. Forty-nine patients have been included until May 2017, and the last patient will be operated on June 14th. Stratification has been performed according to the recruitment centre 3.8 Statistical Methods & Additional Analyses Safety & Efficacy Outcomes: Analyses will be by intention to treat, including all randomised patients. Difference in treatment effect will be evaluated with hazard ratio between the treatment groups, and the corresponding confidence interval will be calculated. For secondary outcomes, the incidence of comorbidities during follow-up will be evaluated using time-to-event models, and for continuous variables mixed models will be used to evaluate differences between the treatment groups. Incremental cost-effectiveness analysis will be conducted by calculating the incremental cost-effectiveness ratio (ICER; dividing the between-group difference in costs with the between-group difference in quality-adjusted life-years (QALYs) as well as life-years). Probabilistic sensitivity analysis will be conducted and results presented in an ICER scatterplot and cost-effectiveness acceptability curve. Follow-Up Clinical Data Collection: Study point are 6 weeks, 1 year, 2 years, and 5 years after the start of intervention. Weight, quality of life, and adverse events, as well as clinical data regarding treatments for co-morbidities. Blood sampling for assessment of nutritional deficiencies, glucose control, blood lipids and inflammation will be collected at baseline and 1, 2 and 5 years. Cognitive functions: Assessments will be performed at baseline and 1 and 2 years after start of intervention. Register-Based Data Collection and Health-Economic Outcomes: Collection and analysis of Swedish national health care and other official registries We decided in the Study Steering Committee to change time points for long term follow up to be 5, 10 and 15 years after treatment initiation to better comply with standard schedules for clinical follow up in registers (instead of 7, 12 and 17y after treatment initiation).

Official Title
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AMOS2 (Adolescent Morbid Obesity Surgery)

Conditions
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Obesity, Diabetes, Hypertension, Steatohepatitis, Inflammation

Intervention / Treatment
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* Procedure: Laparoscopic Roux-en-Y gastric bypass
* Procedure: Intense conservative treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 13-16 years BMI >35 Failed comprehensive treatment for obesity > 1 year Passing assessment of psychologist Tanner 3 or more Exclusion Criteria: Monogenic obesity (for example Prader Willis, Laurence Moon-Bardet-Biedl) Obesity secondary to brain injury Severely mentally disabled Not eligible for general anesthesia Psychotic or other major psychiatric illness Previous major gastrointestinal surgery

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomisation between Bariatric surgery (mainly Roux-en-Y gastric bypass) or Intensive Medical treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bariatric surgery<br>Roux-en-Y gastric bypass surgery | Procedure: Laparoscopic Roux-en-Y gastric bypass<br>* Bariatric surgery with Roux-en-Y gastric bypass as preferred option, possible laparoscopic Vertical Sleeve Gastrectomy<br>|
| Active Comparator: Intense conservative treatment<br>Intense conservative treatment. 8 week LCD followed by outpatient visits 1/ month | Procedure: Intense conservative treatment<br>* Intense medical treatment for obesity (behavioral treatment, dietary intervention, exercise, medication etc) 8 week period of Low Calorie Diet. Treatment intensity about 1 visit a month over 2 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index (kg/m2) |  | 2 years after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic control | Glucose control (fP-Glc, fs-Insulin, HbA1c, Oral glucose tolerance test), Blood lipids (HDL, LDL, TG, Apo A, Apo B), Blood pressure (systolic and diastolic), Inflammation (LPK, CRP, Adiponectin, IL-6, TNF-alfa), liver function tests (AST, ALT, ALP, Bil) | 2, 5, 10 and 15 years after treatment initiation | 
| Quality of life, generic | Mental and physical quality of life assessed by Short Form-36 (score 0-100, lower= more disability) | 2, 5, 10 and 15 years after treatment initiation | 
| Obesity-specific quality of life | Obesity Problem scale- 9 items (score 0-100, higher score= more psychosocial impairment) | 2, 5, 10 and 15 years after treatment initiation | 
| Socioeconomic development | Education, civil status, number of children, income, sick leave (from national registries) | 5, 10 and 15 years after treatment initiation | 
| Health care consumption | In hospital care, outpatient care, prescribed medications; from national registries | 2, 5, 10 and 15 years after treatment initiation | 
| Skeletal maturation and quality | Bone mineral content and bone mineral density will be assessed as well as blood markers for bone formation and resorption | 2, 5, 10 and 15 years after treatment initiation | 
| Addictive behavior | Alcohol consumption, blood markers for alcohol consumption, drugs, brain response to visual stimuli | 2, 5, 10, 15 years after treatment initiation | 
| Mental health | Depression, anxiety, self esteem, stability in neuropsychiatric disease (ADHD, ADD), psychiatric illness, OCD | 2, 5, 10 and 15 years after treatment initiation | 
| Adverse events | Any adverse event (physical, mental or other) | 2, 5, 10 and 15 years after treatment initiation | 
| Eating function | Assessment of meal pattern, dietary composition and gastrointestinal symptoms in relation to eating | 2, 5, 10 and 15 years after treatment initiation | 
| Energy expenditure | Doubly labelled water, basic metabolic rate, 24h energy expenditure chamber 5 years | 5 years after treatment initiation | 
| Body Mass Index, body weight, height. Additional assessments of primary outcome | Weight (kg) and height (m) will be combined to report BMI in kg/m2 | 5, 10 and 15 years after treatment initiation | 
| Cognitive Function | General cognitive functioning (IQ test- WISC-IV Wechsler Intelligence Scale for Children) Scale 1-200 where lower score means worse) | 1, 2 and 5 years after treatment initiation | 
| Working memory | Memory (D-KEFS-Delis-Kaplan Executive Function System) several subscales 0-15, lower value means worse | 1, 2 and 5 years after treatment initiation | 
| Attention | Attention (NEPSY- NEuroPSYcologic examination). Separate subscales for executive function and attention, language, memory and learning, sensorimotor, visuospatial processing, and social perception. Lower value means worse. | 1, 2 and 5 years after treatment initiation |