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

Obesity Clinical Trial

Official title:

A Parallel Cohort Controlled Trial of Outcome of Nonalcoholic Steatohepatitis in Adolescents After Bariatric Surgery vs. Comprehensive Lifestyle Intervention (NASH ABC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02412540
• Other study ID #: NASH ABC
• Status: Completed
• Phase: N/A
• Start date: April 23, 2015
• Est. completion date: March 2, 2021

Study information

• Verified date: November 2021
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The investigators have designed a rigorously controlled study designed to evaluate NASH outcomes in two parallel cohorts: 1) severely obese adolescents with NASH who have chosen to undergo WLS (specifically VSG) for clinical indications compared to 2) a control group of severely obese adolescents with NASH enrolled in a CLI offered as part of this study. The study will provide the best evidence to date of the effectiveness of WLS and CLI in treating NASH in adolescents with body mass index (BMI) ≥ 35 kg/m2. The investigators will also concurrently collect health-care utilization data to enable subsequent cost-effectiveness analyses (CEA) to evaluate the cost-effectiveness of WLS vs. CLI intervention in severely-obese adolescents with NASH. If the investigators' data support our hypothesis that WLS yields superior results, this will set the stage for randomized studies (if needed) and translational studies of weight loss-independent biological mechanism(s) unique to WLS, which may include specific changes in bile acid signaling and in the intestinal microbiome. The latter would facilitate developing novel pharmacotherapies accessible to younger or less obese children with NASH to whom WLS is not applicable. Cumulatively, this study has the potential to yield significant improvements in medical and quality of life (QOL) outcomes for a large proportion of pediatric patients with NASH and to reduce long term health care costs by identifying effective treatment options and decreasing progression to cirrhosis and end-stage liver disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: March 2, 2021
• Est. primary completion date: March 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 19 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis
• Obesity

Intervention

Behavioral:
• Comprehensive Lifestyle Intervention
Dietary, behavioral and activity interventions designed to reduce weight.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Resolution of NASH: Proportion of subjects achieving "not NASH" histological diagnosis	Proportion of subjects achieving "not NASH" histological diagnosis at the end of the study.	12 months
Secondary	Reduction in mean NAS	decrease in overall histological activity as measured by reduction in mean NAS.	12 months
Secondary	Decrease in steatosis	Decrease in NAS score	12 months
Secondary	Composite decrease in weight	Decrease in BMI, weight and waist circumference.	12 months
Secondary	Composite Quality of Life (QOL) Measures	Change in generic health-related and weight-specific QOL measures Pediatric Quality of Life Inventory and Impact of Weight on Quality of Life (IWQOL-Kids©)).	12 months
Secondary	Liver enzymes	Decrease in serum alanine (ALT) & asparate aminotransferase (AST), gamma-glutamyl trans-peptidase (GGT) level.	12 months
Secondary	Liver enzymes	Normalization of ALT (defined as <26 U/L for males and <22 U/L for females).	12 months