Low Carbohydrate Diet: The Effects on Non Alcoholic Fatty Liver Disease in Obese Teens With Metabolic Syndrome

NCT02358928 | Completed DMC

• 1 other identifier: STU 082013 020
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Concurrent with the rising prevalence of childhood obesity, the co-morbid condition of non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease among children. NAFLD is characterized by accrual of excess triglycerides (TG) in the liver that leads to inflammation, fibrosis, and cirrhosis. One-third of the pediatric population has NAFLD, a disease strongly associated with insulin-resistance and metabolic-syndrome (Met-S). NAFLD is predicted to become the leading cause of liver transplantation in adults by 2030. Current understanding of NAFLD indicates that presence of excess TG in liver is an absolute requirement for disease progression. First-line therapy for NAFLD is focused on decreasing adiposity and improving insulin sensitivity through diet and exercise. Recent adult data indicate that dietary carbohydrate-restriction is more effective at reducing hepatic TG-content than traditional calorie-restriction. Few studies have been conducted to establish resolution of hepatic steatosis by any intervention. Such studies in pediatrics are primarily limited by a need for liver biopsy. However, hepatic proton magnetic resonance spectroscopy (H-MRS) is a new innovative tool used to quantitatively measure hepatic TG content in a non-invasive manner. The primary aim is to compare the impact of dietary weight loss via carbohydrate-restriction and calorie-restriction on hepatic TG-content quantified by H-MRS in obese children with biopsy-proven NAFLD and Met-S. This IRB approved protocol is a randomized control study. The investigators will recruit subjects from the Center for Obesity and its Consequences in Health and the pediatric gastroenterology clinics between the ages of 11-17 years who meet criteria for NAFLD and Met-S. A H-MRS will be obtained in each subject prior to the start of dietary intervention. Fifty-four subjects will be randomized to either a carbohydrate-restricted or calorie-restricted diet for 6 months with no change in baseline activity. A repeat H-MRS will be compared to baseline to determine the whether dietary carbohydrate-restriction is superior to calorie-restriction for reducing hepatic TG content. The investigators believe that subjects on the carbohydrate-restricted diet will have marked decrease in hepatic TG content compared to those in the calorie-restricted diet given the same degree of reduction in body mass index.

Conditions

NAFLD; Fatty Liver; Obesity; Metabolic Syndrome

Keywords

NAFLD; Metabolic syndrome; Hepatic Magnetic Resonance Spectroscopy; Obesity

Outcome Measures

Primary Outcomes (1)

• HepaticTrigylceride Content quantified on proton magnetic spectroscopy (H-MRS)

  To compare the impact of dietary weight loss via carbohydrate-restriction and calorie-restriction on hepatic TG content quantified by H-MRS in obese children with biopsy-proven NAFLD and Met-S.

  1 year

Secondary Outcomes (3)

• BMI Z-score

  1 year

• Cytokeratin-18

  1 year

• ALT (alanine transaminase)

  1 year

Study Arms (2)

Low calorie diet

OTHER

Calorie-restricted diet is composed of 50% carbohydrate, 15-20% protein and 30-35% fat.

Other: Diet Intervention

Low carbohydrate diet

OTHER

Carbohydrate-restricted diet is composed of 20% carbohydrates, 35% protein and 45% fat.

Other: Diet Intervention

Interventions

Diet Intervention OTHER

Low calorie diet; Low carbohydrate diet

Eligibility Criteria

• Age: 11 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 11 - 17 years
• Male and Female subjects
• BMI \>= 95th percentile according to CDC body mass index chart for age and gender
• Must be willing to participate and undergo "willingness to change" evaluation
• Metabolic Syndrome(MetS) which is defined when 3 of the following are met:
• Central adiposity (waist circumference ≥90th% for age and sex)
• Hypertriglyceridemia (triglycerides ≥ 110mg/dl)
• Low HDL cholesterol ≤40mg/dl
• Elevated blood pressure systolic or diastolic blood pressure \> 90th % adjusted for age, sex and height or ≥ 130/85
• IFG (Impaired fasting glucose ≥ 100mg/dl or elevated HOMA- IR ≥3.16)
• ALT greater than 60 U/L and Non Alcoholic Fatty Liver Disease based on histologic confirmation on liver biopsy (minimum of 5% of hepatocytes with macrovesicular fat) obtained within 6 months before randomization

You may not qualify if:

• Those patients with a history of poor compliance or adherence to energy restriction diets
• Patients on medications that could alter appetite including glucocorticoids, psychostimulants (Vyvanse, Adderall), psychotropic medications (Zoloft, Risperdal), and antihyperglycemic medications (metformin, sulfonylurea)
• Patients with the following illnesses:
• Type 2 diabetes
• Renal disease
• Mental diseases (mood, psychotic and anxiety disorders)
• Developmental delay
• Autism and autism spectrum disorders
• Any liver disease except for non alcoholic fatty liver (NAFLD)
• Metabolic disorders (tyrosinemia, glycogen storage disease, lysosomal disorders)
• Congenital heart disease
• Myopathies or muscular disorders/disability
• Patients who follow a (cultural or religious) vegetarian lifestyle as this would not be compatible with Carbohydrate Restriction (need for high quality protein)
• Prepubertal patients defined by a tanner stage of 1
• Current or history of significant alcohol consumption

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UTexasSouthwestern/Childrens Medical Center

Dallas, Texas, 75234, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver; Obesity; Metabolic Syndrome

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Study Officials

• Charina Ramirez, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 29, 2015
• First Posted: February 9, 2015
• Study Start: July 1, 2014
• Primary Completion: August 18, 2016
• Study Completion: August 18, 2016
• Last Updated: January 28, 2022

Record last verified: 2022-01

Locations

US (1)