Randomized Clinical Trial; Medical vs Bariatric Surgery for Adolescents (13-16 y) With Severe Obesity
- Conditions
- SteatohepatitisInflammationDiabetesHypertensionObesity
- Interventions
- Procedure: Laparoscopic Roux-en-Y gastric bypassProcedure: Intense conservative treatment
- Registration Number
- NCT02378259
- Lead Sponsor
- Göteborg University
- Brief Summary
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
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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 50
- Age 13-16 years
- BMI >35
- Failed comprehensive treatment for obesity > 1 year
- Passing assessment of psychologist
- Tanner 3 or more
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bariatric surgery Laparoscopic Roux-en-Y gastric bypass Roux-en-Y gastric bypass surgery Intense conservative treatment Intense conservative treatment Intense conservative treatment. 8 week LCD followed by outpatient visits 1/ month
- Primary Outcome Measures
Name Time Method Body Mass Index (kg/m2) 2 years after treatment initiation
- Secondary Outcome Measures
Name Time Method Socioeconomic development 5, 10 and 15 years after treatment initiation Education, civil status, number of children, income, sick leave (from national registries)
Health care consumption 2, 5, 10 and 15 years after treatment initiation In hospital care, outpatient care, prescribed medications; from national registries
Metabolic control 2, 5, 10 and 15 years after treatment initiation 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)
Addictive behavior 2, 5, 10, 15 years after treatment initiation Alcohol consumption, blood markers for alcohol consumption, drugs, brain response to visual stimuli
Adverse events 2, 5, 10 and 15 years after treatment initiation Any adverse event (physical, mental or other)
Cognitive Function 1, 2 and 5 years after treatment initiation General cognitive functioning (IQ test- WISC-IV Wechsler Intelligence Scale for Children) Scale 1-200 where lower score means worse)
Working memory 1, 2 and 5 years after treatment initiation Memory (D-KEFS-Delis-Kaplan Executive Function System) several subscales 0-15, lower value means worse
Obesity-specific quality of life 2, 5, 10 and 15 years after treatment initiation Obesity Problem scale- 9 items (score 0-100, higher score= more psychosocial impairment)
Mental health 2, 5, 10 and 15 years after treatment initiation Depression, anxiety, self esteem, stability in neuropsychiatric disease (ADHD, ADD), psychiatric illness, OCD
Energy expenditure 5 years after treatment initiation Doubly labelled water, basic metabolic rate, 24h energy expenditure chamber 5 years
Quality of life, generic 2, 5, 10 and 15 years after treatment initiation Mental and physical quality of life assessed by Short Form-36 (score 0-100, lower= more disability)
Eating function 2, 5, 10 and 15 years after treatment initiation Assessment of meal pattern, dietary composition and gastrointestinal symptoms in relation to eating
Attention 1, 2 and 5 years after treatment initiation 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.
Skeletal maturation and quality 2, 5, 10 and 15 years after treatment initiation Bone mineral content and bone mineral density will be assessed as well as blood markers for bone formation and resorption
Body Mass Index, body weight, height. Additional assessments of primary outcome 5, 10 and 15 years after treatment initiation Weight (kg) and height (m) will be combined to report BMI in kg/m2
Trial Locations
- Locations (3)
Sahlgrenska University hospital
🇸🇪Gothenburg, Sweden
SkĂĄne University Hospital
🇸🇪Malmö, Sweden
Karolinska University hospital
🇸🇪Stockholm, Sweden