Controlled Trial of WLS vs. CLI for Severely Obese Adolescents With NASH

This is an interventional treatment trial for Obesity Read More

Inclusion Criteria:

• Adolescents ages 12-19 years (range as defined by World Health Organization).
• BMI ≥ 35 to 69 kg/m2 (minimum BMI per current guidelines for WLS in adolescents). An upper limit of BMI was set to avoid rare outliers in BMI.
• Meet current standard of care eligibility criteria for adolescent WLS.
• Liver biopsy for clinical indication to evaluate for NASH within 1 year of enrollment. Biopsy must confirm definite or borderline NASH with a minimum histological NASH Activity Score of ≥ 3.
• No evidence of any other liver disease by history, screening tests or histological evaluation.
• Written informed consent from parent/legal guardian and informed assent from the adolescent

Exclusion Criteria:

• Evidence of other chronic liver disease: autoimmune hepatitis; hepatitis B; hepatitis C; hemochromatosis; alpha-1-antitrypsin (A1AT) deficiency; Wilson disease; use of medications known to cause fatty liver for > 2 consecutive weeks in past year (i.e. systemic glucocorticoids, tetracycline, anabolic steroids, valproic acid); alcohol intake >10 gm/day females & >20 gm/day males.
• Non-compensated liver disease with any of the following: hemoglobin <10 g/dL; white blood cell count <3,500 cells/mm3, platelet count <130,000 cells/mm3 of blood, direct bilirubin >1.0 mg/dL, total bilirubin >3 mg/dL, albumin <3.2 g/dL, international normalized ratio (INR) >1.4
• Active psychiatric disorder that would prevent eligibility for WLS or impede adherence to CLI, including clinically significant depression (hospitalization or suicidal ideation) in past 12 months.
• Any medical condition preventing eligibility for WLS including but not limited to micronutrient deficiencies (e.g. iron) refractory to medical therapy or inflammatory bowel disease.
• Poorly controlled Type 2 diabetes mellitus (T2DM) defined as hemoglobin A1C (HgbA1c) > 10%.
• Initiation of high dose vitamin E (>400 IU per day) or other medications which could alter NASH histology at any time after baseline liver biopsy or during the trial. Stable dose of vitamin E that was started 12 months or more prior to biopsy is allowed.
• Weight reduction of >5% between baseline liver biopsy and enrollment, as weight loss >5% may change NASH severity.
• Inability or failure to provide informed assent/consent
• Current enrollment in another clinical trial or receipt of an investigational study drug within 6 months prior to the baseline liver biopsy
• Any female who is currently nursing, planning a pregnancy, known or suspected to be pregnant, or has a positive pregnancy screen
• Inability to travel to study site at intervals necessary for clinical interventions (CLI or WLS).
• Prior history of WLS.