This phase 2 trial is a single-site sequential, multiple assignment, randomized trial (SMART) to test and construct a high-quality adaptive intervention of essential amino acids (EAA) and/or Low Sugar Diet for children with metabolic dysfunction associated steatotic liver disease (MASLD) and increased cardiometabolic risk. The basis for the trial includes high-quality pilot data in both EAA for hepatic steatosis and a low sugar diet for hepatic steatosis. In the trial, children aged 11-17 years old will be eligible to participate if their BMI is greater than or equal to 95th% at baseline and hepatic steatosis is greater than or equal to 8% at baseline by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) because this is the most common age group diagnosed with metabolic-dysfunction associated steatotic liver disease.
Metabolic-dysfunction associated steatotic liver disease is defined as the presence of abnormal hepatic stored triglycerides (hepatic steatosis), with one or more of 5 cardiometabolic factors (increased body mass index or waist circumference, hyperglycemia, hypertriglyceridemia, or low HDL) and no other chronic liver disease. Pediatric hepatic steatosis is central to long-term metabolic and cardiovascular health because of the relation of hepatic steatosis to the development of other major diseases. Hepatic steatosis limits the normal metabolic role of insulin and plays a key role in the future development of the metabolic syndrome, and is the strongest predictor for the development of type 2 diabetes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
102
EAA supplement contains the following formulation: histidine, isoleucine, leucine, lysine, phenylalanine, threonine, and valine
The Low Sugar Diet uses the adapted and extended Social Cognitive Theory (SCT) guided low sugar intervention. The registered dietitian nutritionist (RDN) helps families to identify foods high in sugar and to identify acceptable replacements in order to remove foods and drinks high in free sugar from the home and replacement with low or no free sugar containing similar foods.
Corewell Health West
Grand Rapids, Michigan, United States
Change in hepatic steatosis
Change in hepatic steatosis by magnetic resonance imaging (MRI)
Time frame: Baseline to 24 weeks
Change in fasting triglyceride
Change in triglyceride in mg/dL
Time frame: Baseline, 12 and 24 weeks
Change in HDL
Change in HDL mg/dL
Time frame: Baseline, 12 and 24 weeks
Change in VLDL-triglyceride
Very-low-density-lipoprotein triglyceride
Time frame: Baseline, 12 and 24 weeks
Change in Waist circumference
Change in Waist circumference in cm
Time frame: Baseline, 12 and 24 weeks
Change in body weight
Change in weight in kilograms
Time frame: Baseline, 12 and 24 weeks
Change in BMI Z Score
Change in body mass index z-score
Time frame: Baseline, 12 and 24 weeks
Change in Alanine Aminotransferase (ALT)
Change in ALT
Time frame: Baseline, 12 and 24 weeks
Aspartate Aminotransferase (AST)
Change in AST
Time frame: Baseline, 12 and 24 weeks
Gamma glutamyl transferase (GGT)
Change in GGT
Time frame: Baseline, 12 and 24 weeks
Systolic blood pressure
Change in systolic blood pressure mg/dL
Time frame: Baseline, 12 and 24 weeks
Diastolic blood pressure
Change in diastolic blood pressure (mg/dL)
Time frame: Baseline, 12 and 24 weeks
Hemoglobin A1c
Change in hemoglobin A1c
Time frame: Baseline, 12 and 24 weeks
HOMA-IR
Change in homeostatic model assessment of insulin resistance (HOMA-IR)
Time frame: Baseline, 12 and 24 weeks
Adverse events
Number of adverse events compared between arms of the study
Time frame: Baseline, 12 and 24 weeks
Percent responders
Percent of participants who reduce hepatic steatosis in the group that start with low sugar diet compared to the group that starts with EAA intervention
Time frame: Baseline to 24 weeks
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