Moderately Carbohydrate-restricted Diet to Treat NAFLD in Adolescents

NCT05268042 | Recruiting

• 2 other identifiers: Pediatric NAFLD studyR01DK128457
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a 6-month randomized clinical trial with two arms: moderately carbohydrate-restricted diet and a fat-restricted control diet. This 6-month study will have 2 phases: a 12-week controlled feeding phase and a 12-week "free living" phase. During the controlled feeding phase, all food will be provided to the families of the participants for the entirety of the 12 weeks. Participants (n=80) will have been diagnosed with NAFLD based on the presence of current evidence of active disease, which will be determined by the ongoing presence of hepatic steatosis estimated by diffusely echogenic liver via ultrasound suggestive of fatty liver and a serum alanine aminotransferase (ALT) level of 45 U/L or greater. All participants will be children and adolescents age 10-17 yrs.; will have an HbA1c \<7.0; and will be overweight or obese (BMI \>85th percentile). It is anticipated that most participants will be sedentary. The investigators will inquire as to routine physical activity at screening. All participants will be asked to maintain their usual level of physical activity throughout the study. Physical activity will be monitored via a smart watch provided to each participant at the beginning of the study, and participants will be queried weekly by the study dietitian regarding changes in physical activity. Participants who use oral contraceptives will be asked to maintain consistent use of these preparations throughout the study. Hormone use will be examined as a potential covariate in statistical analyses.

Conditions

Non-Alcoholic Fatty Liver Disease; Obesity

Keywords

NAFLD; Obesity; Insulin sensitivity

Outcome Measures

Primary Outcomes (3)

• Hepatic lipid

  Hepatic lipid will be measured using MRI and Magnetic resonance spectroscopy (MRS).

  Baseline

• Hepatic lipid

  Hepatic lipid will be measured using MRI and MRS.

  3 months

• Hepatic lipid

  Hepatic lipid will be measured using MRI and MRS.

  6 months

Secondary Outcomes (7)

• Hepatic insulin sensitivity

  Baseline

• Hepatic insulin sensitivity

  3 months

• Plasma metabolome

  Baseline

• Plasma metabolome

  3 months

• Body composition

  Baseline

Study Arms (2)

Moderately carbohydrate-restricted diet

EXPERIMENTAL

For this study, the investigators will use the low glycemic, moderately carbohydrate-restricted diet that the investigators have previously shown is associated with depletion of hepatic lipid content, and improvement in insulin resistance in adolescents with NAFLD. This diet has a macronutrient composition of approximately 25% energy from carbohydrate, 20% energy from protein, and 55% energy from fat. No food group is excluded in this diet prescription; however, the diet emphasizes low-glycemic sources of carbohydrate, and includes mainly whole foods (vegetables, fruits, whole grains) with minimal highly processed grain products and added sugar. Protein foods will include meat, poultry, fish, eggs, and whey protein supplements if necessary. Fat-containing foods will include olive, coconut, and nut oils; butter; tree nuts and nut butters; cheese; cream; coconut milk; avocados; and the fat found in meat. A number of full-fat dairy products will be included.

Other: Moderately carbohydrate-restricted diet

Fat-restricted diet

ACTIVE COMPARATOR

The fat-restricted, control diet will consist of approximately 60% carbohydrate, 20% protein, 20% fat. Participants will be given low-fat foods, whole-grain foods, fruits, and vegetables. The meal plans will minimize cholesterol, high-fat foods, high-cholesterol foods, processed starches, and added sugar, and will provide \<2300 mg/day sodium. Saturated fat will be limited to 10% of total fat intake, and all dairy products will be fat-free (or low fat).

Other: Fat-restricted diet

Interventions

Moderately carbohydrate-restricted diet OTHER

For this study, the investigators will use the low glycemic, moderately carbohydrate-restricted diet that the investigators have previously shown is associated with depletion of hepatic lipid content, and improvement in insulin resistance in adolescents with NAFLD. This diet has a macronutrient composition of approximately 25% energy from carbohydrate, 20% energy from protein, and 55% energy from fat. No food group is excluded in this diet prescription; however, the diet emphasizes low-glycemic sources of carbohydrate, and includes mainly whole foods (vegetables, fruits, whole grains) with minimal highly processed grain products and added sugar. Protein foods will include meat, poultry, fish, eggs, and whey protein supplements if necessary. Fat-containing foods will include olive, coconut, and nut oils; butter; tree nuts and nut butters; cheese; cream; coconut milk; avocados; and the fat found in meat. A number of full-fat dairy products will be included.

Moderately carbohydrate-restricted diet

Fat-restricted diet OTHER

The fat-restricted, control diet will consist of approximately 60% carbohydrate, 20% protein, 20% fat. Participants will be given low-fat foods, whole-grain foods, fruits, and vegetables. The meal plans will minimize cholesterol, high-fat foods, high-cholesterol foods, processed starches, and added sugar, and will provide \<2300 mg/day sodium. Saturated fat will be limited to 10% of total fat intake, and all dairy products will be fat-free (or low fat).

Fat-restricted diet

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• clinical-pathological diagnosis of NAFLD and current evidence of active disease, which will be determined by the ongoing presence of hepatic steatosis estimated by diffusely echogenic liver via ultrasound suggestive of fatty liver and a serum alanine aminotransferase (ALT) level of 45 U/L or greater.
• age 10 -17 yrs
• overweight or obese (BMI \>75th percentile).

You may not qualify if:

• pregnancy
• HbA1c \>7%
• history of parenteral nutrition
• hepatic virus infections (HCV RNA-polymerase chain reaction negative; hepatitis A, B, C, D, E, and G; cytomegalovirus; and Epstein-Barr virus)
• use of medications known to induce steatosis (e.g. valproate, amiodarone, or prednisone), elevate liver enzymes, or affect body weight and carbohydrate metabolism (within the last 6months)
• autoimmune liver disease
• metabolic liver disease
• Wilson's disease
• genetic conditions (e.g. glycogen storage disorder) leading to hepatic steatosis;
• history of bariatric surgery
• participants and parents/guardians unwilling or unable to give informed consent, accept random assignment, attend dietary counseling sessions, adhere to treatment prescription, or complete study measures
• inability to speak and comprehend English (participants and parents/guardians)
• currently receiving intense lifestyle modification treatment
• estimated Glomerular Filtration Rate (eGFR) \<60
• alcohol, tobacco or recreational drug use

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35226, United States

RECRUITING

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity; Insulin Resistance

Interventions

Diet, Fat-Restricted

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Central Study Contacts

Alex Luzuriaga-McPherson

CONTACT

205-934-6299; alexandramcpherson@uabmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a dietary intervention. As such, participants will likely know what diet prescription they are randomized to during the intervention. All investigators and individuals responsible for data analysis will be blinded to participant group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The objective of this parallel arm, randomized clinical trial is to use a 6-month family-based intervention with 2 phases, a 12-week controlled feeding and 12-week free-living phase, to examine the effects of weight maintaining, moderately carbohydrate-restricted vs fat-restricted diets in adolescents with NAFLD on depletion of hepatic lipid, improvement in hepatic insulin sensitivity, and changes in the plasma metabolome.

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: March 7, 2022
• Study Start: May 1, 2022
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: May 20, 2025

Record last verified: 2025-05

Locations

US (1)