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

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ClinicalTrials.gov Identifier: NCT02412540
Recruitment Status : Recruiting
First Posted : April 9, 2015
Last Update Posted : September 3, 2018
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Tracking Information
First Submitted Date  ICMJE April 1, 2015
First Posted Date  ICMJE April 9, 2015
Last Update Posted Date September 3, 2018
Study Start Date  ICMJE April 2015
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 6, 2015)
  • Histology Endpoint: Proportion of subjects achieving greater than 2 point reduction in NASH activity score (NAS) [ Time Frame: 12 months ]
    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.
  • Biomarker Endpoint [ Time Frame: 12 months ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02412540 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2015)
  • Resolution of NASH: Proportion of subjects achieving "not NASH" histological diagnosis [ Time Frame: 12 months ]
    Proportion of subjects achieving "not NASH" histological diagnosis at the end of the study.
  • Reduction in mean NAS [ Time Frame: 12 months ]
    decrease in overall histological activity as measured by reduction in mean NAS.
  • Decrease in steatosis [ Time Frame: 12 months ]
    Decrease in NAS score
  • Composite decrease in weight [ Time Frame: 12 months ]
    Decrease in BMI, weight and waist circumference.
  • Composite Quality of Life (QOL) Measures [ Time Frame: 12 months ]
    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©)).
  • Liver enzymes [ Time Frame: 12 months ]
    Decrease in serum alanine (ALT) & asparate aminotransferase (AST), gamma-glutamyl trans-peptidase (GGT) level.
  • Liver enzymes [ Time Frame: 12 months ]
    Normalization of ALT (defined as <26 U/L for males and <22 U/L for females).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Controlled Trial of WLS vs. CLI for Severely Obese Adolescents With NASH
Official Title  ICMJE A Parallel Cohort Controlled Trial of Outcome of Nonalcoholic Steatohepatitis in Adolescents After Bariatric Surgery vs. Comprehensive Lifestyle Intervention (NASH ABC)
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.
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Obesity
  • Nonalcoholic Steatohepatitis
  • Nonalcoholic Fatty Liver Disease
Intervention  ICMJE Behavioral: Comprehensive Lifestyle Intervention
Dietary, behavioral and activity interventions designed to reduce weight.
Study Arms  ICMJE
  • No Intervention: Weight Loss Surgery
    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.
  • Experimental: Comprehensive Lifestyle Intervention
    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.
    Intervention: Behavioral: Comprehensive Lifestyle Intervention
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 6, 2015)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 19 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Meghan McNeill, BS (513)636-6226 Meghan.McNeil@cchmc.org
Contact: Stavra Xanthakos, MD (513)636-4680 Stavra.Xanthakos@cchmc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02412540
Other Study ID Numbers  ICMJE NASH ABC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Hospital Medical Center, Cincinnati
Study Sponsor  ICMJE Children's Hospital Medical Center, Cincinnati
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Stavra Xanthakos, MD Children's Hospital Medical Center, Cincinnati
PRS Account Children's Hospital Medical Center, Cincinnati
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP