Comparison Between the Efficacy of Residential and Ambulatory Weight Loss Programs for Pediatric Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease worldwide, paralleling the obesity pandemic. Secondary to increasing rates of obesity in children and adolescents, the prevalence of NAFLD has more than doubled in the last decades and is now the most common pediatric liver disease.

At present, lifestyle modification by dietary intervention and increasing physical activity is the mainstay of treatment for pediatric NAFLD. Several studies have shown that lifestyle intervention and weight loss improve non-invasive markers of NAFLD. To the investigator's knowledge, data on fibrosis regression following lifestyle treatment in children and adolescents were lacking. The investigators therefore performed a prospective cohort study to investigate the impact of residential lifestyle treatment on liver steatosis and fibrosis in obese children and adolescents.

As a follow-up, the investigators now aim to compare these findings with a cohort of well-characterized patients undergoing multidisciplinary, yet ambulatory, weight loss treatment. As such, the investigators will compare the outcomes in two prospective patient cohorts in this non-randomized observational study.

Study Overview

• Status: Recruiting
• Conditions: Pediatric Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Behavioral: Lifestyle management

• Study Type: Observational
• Enrollment (Estimated): 850

Contacts and Locations

• Study Contact: Name: Ruth De Bruyne, MD, PhD; Phone Number: 003293322966; Email: ruth.debruyne@uzgent.be

Study Locations

• Belgium
  • East-Flanders
    • Gent, East-Flanders, Belgium, 9000
      • Recruiting
      • AZ Jan Palfijn
      • Contact: Nele Baeck, MD
      • Principal Investigator: Nele Baeck, MD
    • Gent, East-Flanders, Belgium, 9000
      • Recruiting
      • University Hospital Gent
      • Contact: Ruth De Bruyne, MD, PhD; Phone Number: 003293323966; Email: ruth.debruyne@uzgent.be
      • Contact: Sander Lefere, MD, PhD; Email: sander.lefere@ugent.be
      • Principal Investigator: Sander Lefere, MD, PhD
      • Principal Investigator: Anja Geerts, MD, PhD
      • Principal Investigator: Ruth De Bruyne, MD, PhD
  • West-Flanders
    • De Haan, West-Flanders, Belgium, 8420
      • Recruiting
      • Zeepreventorium
      • Contact: Ellen Dupont, MD
      • Principal Investigator: Ellen Dupont, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children and adolescents with obesity (BMI higher than the 95th weight percentile)

Description

Inclusion Criteria:

• Enrolled in the lifestyle management program for obesity in one of the participating centres

Exclusion Criteria:

• Syndromic obesity
• Evidence of liver disease of other causes (viral, auto-immune, genetic)
• Average daily alcohol consumption of >20g/day
• Unvalid screening Fibroscan
• Treatment with drugs which can induce liver steatosis or fibrosis (e.g. systemic corticosteroids, methotrexate)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Residential treatment; Patients administered for residential treatment of severe obesity will be included. Patients are treated according to standard of care in a multimodal program, focusing on increasing the level of physical activity, dietary intervention, acquiring healthy eating habits, and psychological support. Residential treatment is possible for a duration of maximum 1 year.	Behavioral: Lifestyle management; Increasing the level of physical activity, dietary intervention, acquiring healthy eating habits, and psychological support.
Ambulatory treatment; Patients in specific pediatric obesity care pathways will be included. Patients are treated according to standard of care in a multimodal ambulatory program focusing on increasing the level of physical activity, dietary intervention, acquiring healthy eating habits, and psychological support.	Behavioral: Lifestyle management; Increasing the level of physical activity, dietary intervention, acquiring healthy eating habits, and psychological support.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of liver fibrosis	Liver fibrosis will be quantified using Fibroscan, and patients will be divided into disease stages based on published cut-offs.	6 months of lifestyle intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of liver fibrosis	Liver fibrosis will be quantified using Fibroscan, and patients will be divided into disease stages based on published cut-offs.	12 months of lifestyle intervention
Improvement of liver steatosis	Liver steatosis will be quantified using controlled attenuation parameter on the Fibroscan	6 months of lifestyle intervention
Improvement of liver steatosis	Liver steatosis will be quantified using controlled attenuation parameter on the Fibroscan	12 months of lifestyle intervention
Resolution of liver steatosis	Liver steatosis will be quantified using controlled attenuation parameter on the Fibroscan. Resolution of steatosis is identified as CAP <248 dB/m at follow-up in patients with baseline CAP of 248 dB/m or higher.	6 months of lifestyle intervention
Resolution of liver steatosis	Liver steatosis will be quantified using controlled attenuation parameter on the Fibroscan. Resolution of steatosis is identified as CAP <248 dB/m at follow-up in patients with baseline CAP of 248 dB/m or higher.	12 months of lifestyle intervention
Resolution of liver fibrosis	Liver fibrosis will be quantified using Fibroscan. Resolution of fibrosis is identified as liver stiffness <7.0 kPa at follow-up in patients with baseline liver stiffness of 7.0 kPa or higher.	6 months of lifestyle intervention
Resolution of liver fibrosis	Liver fibrosis will be quantified using Fibroscan. Resolution of fibrosis is identified as liver stiffness <7.0 kPa at follow-up in patients with baseline liver stiffness of 7.0 kPa or higher.	12 months of lifestyle intervention
Improvement in ALT	Proportion of patients with at least 30% decrease in serum ALT levels at follow-up, out of the patients with baseline elevated ALT	6 months of lifestyle intervention
Improvement in ALT	Proportion of patients with at least 30% decrease in serum ALT levels at follow-up, out of the patients with baseline elevated ALT	12 months of lifestyle intervention

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Ruth De Bruyne, MD, PhD, University Hospital, Ghent

Publications and helpful links

General Publications

• Lefere S, Dupont E, De Guchtenaere A, Van Biervliet S, Vande Velde S, Verhelst X, Devisscher L, Van Vlierberghe H, Geerts A, De Bruyne R. Intensive Lifestyle Management Improves Steatosis and Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2317-2326.e4. doi: 10.1016/j.cgh.2021.11.039. Epub 2021 Dec 4.
• Nobili V, Vizzutti F, Arena U, Abraldes JG, Marra F, Pietrobattista A, Fruhwirth R, Marcellini M, Pinzani M. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology. 2008 Aug;48(2):442-8. doi: 10.1002/hep.22376.
• Ciardullo S, Monti T, Perseghin G. Prevalence of Liver Steatosis and Fibrosis Detected by Transient Elastography in Adolescents in the 2017-2018 National Health and Nutrition Examination Survey. Clin Gastroenterol Hepatol. 2021 Feb;19(2):384-390.e1. doi: 10.1016/j.cgh.2020.06.048. Epub 2020 Jul 3.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Lifestyle management; NAFLD; Liver fibrosis; Multidisciplinary treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Body Weight; Body Weight Changes; Liver Diseases; Fatty Liver; Weight Loss; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: BC-05660

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The plan can be obtained by contacting the researchers with a worked-out protocol for study in which these data can be used.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No