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

NCT02412540 | Completed DMC

• 1 other identifier: NASH ABC
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine effective treatment and identify diagnostic biomarkers for Nonalcoholic steatohepatitis (NASH). Individuals that take part in the study will be participating in either a weight loss surgery (WLS) group or a comprehensive lifestyle intervention (CLI) group. People in the WLS group will receive vertical sleeve gastrectomy (VSG). The CLI group will receive dietary, activity and behavioral interventions provided by trained study staff.

Conditions

Obesity; Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (2)

• Histology Endpoint: Proportion of subjects achieving greater than 2 point reduction in NASH activity score (NAS)

  Proportion of subjects achieving greater than 2 point reduction in NASH activity score (NAS) across at least two separate histological components of the NAS score (steatosis, inflammation and ballooning) and no worsening of fibrosis stage.

  12 months

• Biomarker Endpoint

  Correlation between presence or absence of histological NASH and combined magnetic resonance (MR) measures and serum cytokeratin 18 (CK18) levels at baseline and 12 month follow-up.

  12 months

Secondary Outcomes (7)

• Resolution of NASH: Proportion of subjects achieving "not NASH" histological diagnosis

  12 months

• Reduction in mean NAS

  12 months

• Decrease in steatosis

  12 months

• Composite decrease in weight

  12 months

• Composite Quality of Life (QOL) Measures

  12 months

Study Arms (2)

Weight Loss Surgery

NO INTERVENTION

Adolescents who will have Weight Loss Surgery and had biopsy-confirmed NASH. The Weight Loss Surgery is not part of the study. The investigators are following the adolescents after the surgery.

Comprehensive Lifestyle Intervention

EXPERIMENTAL

Comprehensive Lifestyle Intervention - Dietary, activity and behavioral interventions. Adolescents who have biopsy-confirmed NASH and wish to participate in a Comprehensive Lifestyle Intervention (26+ contact hours) including individual meetings with a study dietitian, group nutrition classes, behavior management modules and physical activity goals.

Behavioral: Comprehensive Lifestyle Intervention

Interventions

Comprehensive Lifestyle Intervention BEHAVIORAL

Dietary, behavioral and activity interventions designed to reduce weight.

Comprehensive Lifestyle Intervention

Eligibility Criteria

• Age: 12 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Obesity; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Stavra Xanthakos, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2015
• First Posted: April 9, 2015
• Study Start: April 23, 2015
• Primary Completion: March 2, 2021
• Study Completion: March 2, 2021
• Last Updated: November 2, 2021

Record last verified: 2021-11

Locations

US (1)