Nonalcoholic Fatty Liver Disease
Conditions
Keywords
NAFLD, Steatohepatitis, Nonalcoholic Steatohepatitis (NASH), Liver, Diet, Pediatric, Adolescent
Brief summary
This is an investigator initiated study being conducted in equal numbers at two sites, University of California, San Diego (UC San Diego) and Emory University (EU). The purpose of this study is to understand the potential of a low sugar diet for the treatment of nonalcoholic fatty liver disease (NAFLD) in children. Forty boys with NAFLD will be randomly assigned to either an intervention group or a habitual diet control group. The intervention will be a low sugar diet for a period of 8 weeks. The effect of this dietary change will be assessed using advanced magnetic resonance imaging (MRI) testing to measure liver fat.
Interventions
OTHERDietary modification
The intervention is a modification of the family's habitual diet with a low sugar version of their diet.
Sponsors
Emory University
Nutrition Science Initiative
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
11 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Boys age 11-16 years inclusive. * Clinical history consistent with NAFLD. * Biopsy-proven NAFLD * MRI measured Liver Proton Density Fat Fraction ≥10% * alanine aminotransferase (ALT) ≥ 45 u/L * No evidence of any other liver disease by clinical history or histological evaluation. * Written informed consent from parent or legal guardian. * Written informed assent from the child or adolescent.
Exclusion criteria
Exclusions will not be based upon gender, race, or ethnicity. Participants with a current history of the following conditions or any other health issues that make it unsafe for them to participate in the opinion of the Investigators will be excluded from the study: * History of significant alcohol intake (Alcohol Use Disorders Identification Test \[AUDIT\]) or inability to quantify alcohol consumption * Chronic use (more than 2 consecutive weeks) of medications known to cause hepatic steatosis or steatohepatitis in the past year. * The use of other known hepatotoxins within 120 days of baseline * History of total parenteral nutrition (TPN) use in the year prior to screening * History of bariatric surgery or planning to undergo bariatric surgery during the study duration * Significant depression * Non-compensated liver disease with any one of the following hematologic, biochemical, and serological criteria on entry into protocol: * Hemoglobin \< 10 g/dL * White blood cell \< 3,500 cells/mm * Neutrophil count \< 1,500 cells/mm3 of blood * Platelets \< 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 * Evidence of other chronic liver disease * Children who are currently enrolled in a clinical trial or who received an investigational study drug or a medication with the intent to treat NAFLD/NASH in the past 60 days * Contraindications to MRI, e.g. metal in the eyes, implanted electronic devices, aneurysm clips, pacemaker, cochlear implants * Unable to have or complete the MRI exam due to body weight exceeding scanner table limit or girth exceeding scanner bore diameter * Subjects who are not able or willing to comply with the protocol or have any other condition that would impede compliance or hinder completion of the study, in the opinion of the investigator * Families with \> 5 individuals * Failure to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percentage of Liver Fat Measured by Magnetic Resonance Imaging (MRI) in the Intervention Group Compared to Change in the Control Group | Measurements done at baseline and week 8. | The principal objective of this randomized and controlled pilot study is to evaluate whether 8 weeks of a low added sugar diet (\<3%) in boys with NAFLD will change liver fat % measured by MRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Aspartate Aminotransferase (AST) From Baseline to Week 8 | Measurements doen at baseline and week 8 | — |
| Change in Gamma-Glutamyl Transpeptidase (GGT) From Baseline to Week 8 | Measurements done at baseline and week 8 | — |
| Change in Alanine Aminotransferase (ALT) From Baseline to Week 8 | Measurements done at baseline and week 8 | — |
| Change in Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) From Baseline to Week 8 | Measurements done at baseline and week 8 | HOMA-IR was calculated as follows: fasting insulin (µU/mL) x fasting glucose (nmol/L)/22.5 |
| Change in Triglycerides From Baseline to Week 8 | Measurements done at baseline and week 8 | — |
| Change in Insulin From Baseline to Week 8 | Measurements done at baseline and week 8 | — |
Countries
United States
Participant flow
Recruitment details
Children with NAFLD were recruited from two US academic clinical research centers (University of California, San Diego and Emory University)
Pre-assignment details
Boys ages 11 - 16 with biopsy proven NAFLD were randomized
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group Low free sugar diet | 20 |
| Control Group Habitual diet | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Intervention Group | Total | Control Group |
|---|---|---|---|
| Age, Continuous | 12.8 Years STANDARD_DEVIATION 1.8 | 13.0 Years STANDARD_DEVIATION 1.9 | 13.4 Years STANDARD_DEVIATION 1.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 38 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 31 Participants | 15 Participants |
| Race (NIH/OMB) White | 3 Participants | 7 Participants | 4 Participants |
| Region of Enrollment United States | 20 Participants | 40 Participants | 20 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 40 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 2 / 20 | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Change in Percentage of Liver Fat Measured by Magnetic Resonance Imaging (MRI) in the Intervention Group Compared to Change in the Control Group
The principal objective of this randomized and controlled pilot study is to evaluate whether 8 weeks of a low added sugar diet (\<3%) in boys with NAFLD will change liver fat % measured by MRI.
Time frame: Measurements done at baseline and week 8.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Change in Percentage of Liver Fat Measured by Magnetic Resonance Imaging (MRI) in the Intervention Group Compared to Change in the Control Group | Baseline | 22.9 Percentage of liver fat |
| Intervention Group | Change in Percentage of Liver Fat Measured by Magnetic Resonance Imaging (MRI) in the Intervention Group Compared to Change in the Control Group | Week 8 | 14.9 Percentage of liver fat |
| Control Group | Change in Percentage of Liver Fat Measured by Magnetic Resonance Imaging (MRI) in the Intervention Group Compared to Change in the Control Group | Baseline | 19.4 Percentage of liver fat |
| Control Group | Change in Percentage of Liver Fat Measured by Magnetic Resonance Imaging (MRI) in the Intervention Group Compared to Change in the Control Group | Week 8 | 18.0 Percentage of liver fat |
Secondary
Change in Alanine Aminotransferase (ALT) From Baseline to Week 8
Time frame: Measurements done at baseline and week 8
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Change in Alanine Aminotransferase (ALT) From Baseline to Week 8 | Baseline | 103.3 U/L |
| Intervention Group | Change in Alanine Aminotransferase (ALT) From Baseline to Week 8 | Week 8 | 61.3 U/L |
| Control Group | Change in Alanine Aminotransferase (ALT) From Baseline to Week 8 | Baseline | 81.8 U/L |
| Control Group | Change in Alanine Aminotransferase (ALT) From Baseline to Week 8 | Week 8 | 75.2 U/L |
Secondary
Change in Aspartate Aminotransferase (AST) From Baseline to Week 8
Time frame: Measurements doen at baseline and week 8
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Change in Aspartate Aminotransferase (AST) From Baseline to Week 8 | Baseline | 52.0 U/L |
| Intervention Group | Change in Aspartate Aminotransferase (AST) From Baseline to Week 8 | Week 8 | 34.5 U/L |
| Control Group | Change in Aspartate Aminotransferase (AST) From Baseline to Week 8 | Baseline | 43.6 U/L |
| Control Group | Change in Aspartate Aminotransferase (AST) From Baseline to Week 8 | Week 8 | 39.1 U/L |
Secondary
Change in Gamma-Glutamyl Transpeptidase (GGT) From Baseline to Week 8
Time frame: Measurements done at baseline and week 8
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Change in Gamma-Glutamyl Transpeptidase (GGT) From Baseline to Week 8 | Baseline | 44.3 U/L |
| Intervention Group | Change in Gamma-Glutamyl Transpeptidase (GGT) From Baseline to Week 8 | Week 8 | 33.0 U/L |
| Control Group | Change in Gamma-Glutamyl Transpeptidase (GGT) From Baseline to Week 8 | Baseline | 44.1 U/L |
| Control Group | Change in Gamma-Glutamyl Transpeptidase (GGT) From Baseline to Week 8 | Week 8 | 42.8 U/L |
Secondary
Change in Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) From Baseline to Week 8
HOMA-IR was calculated as follows: fasting insulin (µU/mL) x fasting glucose (nmol/L)/22.5
Time frame: Measurements done at baseline and week 8
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Change in Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) From Baseline to Week 8 | Baseline | 8.6 HOMA score |
| Intervention Group | Change in Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) From Baseline to Week 8 | Week 8 | 7.7 HOMA score |
| Control Group | Change in Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) From Baseline to Week 8 | Baseline | 9.2 HOMA score |
| Control Group | Change in Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) From Baseline to Week 8 | Week 8 | 10.2 HOMA score |
Secondary
Change in Insulin From Baseline to Week 8
Time frame: Measurements done at baseline and week 8
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Change in Insulin From Baseline to Week 8 | Baseline | 38.4 mg/dL |
| Intervention Group | Change in Insulin From Baseline to Week 8 | Week 8 | 37.7 mg/dL |
| Control Group | Change in Insulin From Baseline to Week 8 | Baseline | 41.8 mg/dL |
| Control Group | Change in Insulin From Baseline to Week 8 | Week 8 | 43.8 mg/dL |
Secondary
Change in Triglycerides From Baseline to Week 8
Time frame: Measurements done at baseline and week 8
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention Group | Change in Triglycerides From Baseline to Week 8 | Baseline | 121.7 mg/dL |
| Intervention Group | Change in Triglycerides From Baseline to Week 8 | Week 8 | 104.1 mg/dL |
| Control Group | Change in Triglycerides From Baseline to Week 8 | Baseline | 138.9 mg/dL |
| Control Group | Change in Triglycerides From Baseline to Week 8 | Week 8 | 134.3 mg/dL |