SMART Diets for MASLD

Официальное название

A Sequential Multiple Assignment Randomized Trial of Diet Treatments for Hepatic Steatosis and Cardiometabolic Risk in Youth

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Essential Amino Acids Supplementation intervention
  EAA supplement contains the following formulation: histidine, isoleucine, leucine, lysine, phenylalanine, threonine, and valine
• Другое Low sugar diet
  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.

Первичные конечные точки

• Change in hepatic steatosis [Срок оценки: Baseline to 24 weeks]

Вторичные конечные точки (12)

• Change in fasting triglyceride [Срок оценки: Baseline, 12 and 24 weeks]
• Change in HDL [Срок оценки: Baseline, 12 and 24 weeks]
• Change in VLDL-triglyceride [Срок оценки: Baseline, 12 and 24 weeks]
• Change in Waist circumference [Срок оценки: Baseline, 12 and 24 weeks]
• Change in body weight [Срок оценки: Baseline, 12 and 24 weeks]
• Change in BMI Z Score [Срок оценки: Baseline, 12 and 24 weeks]
• Change in Alanine Aminotransferase (ALT) [Срок оценки: Baseline, 12 and 24 weeks]
• Aspartate Aminotransferase (AST) [Срок оценки: Baseline, 12 and 24 weeks]
• Gamma glutamyl transferase (GGT) [Срок оценки: Baseline, 12 and 24 weeks]
• Systolic blood pressure [Срок оценки: Baseline, 12 and 24 weeks]
• Diastolic blood pressure [Срок оценки: Baseline, 12 and 24 weeks]
• Hemoglobin A1c [Срок оценки: Baseline, 12 and 24 weeks]

Критерии участия

Критерии включения

• Children 11 to 17-years-old at the time of consenting
• Hepatic Steatosis by MRI greater than or equal to 8% on baseline MRI
• At least 1 of the following cardiometabolic risk factors: BMI greater than or equal to 85th percentile for age/sex or WC greater than 95th percentile, Abnormal cholesterol or triglyceride levels, Blood pressure BP greater than or equal to 95th percentile OR greater than or equal to 130/80 and/or signs of insulin resistance (Acanthosis Nigricans OR HOMA-IR of greater 2.0 and greater 2.6 in prepubertal and pubertal children, respectively, Fasting Insulin Level of 10 pIU/mL in prepubertal children and of 17 pIU/mL and 13 pIU/mL in pubertal girls and boys, respectively, OR Prediabetes)
• ALT greater than or equal to 40 U/L
• Currently consumes greater than or equal to 2 eight-ounce sugar drinks (or juice) per week.
• Patients of childbearing potential agrees to use adequate one or more effective methods of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Patients who are taking medications that can affect insulin (e.g., metformin, corticosteroids), most be on a stable dosage for at least 3 months prior to enrollment of the trial.
• Written informed consent from parent or legal guardian, assent from child.

Критерии исключения

• Patients with Diagnosed Type 2 or Type 1 Diabetes Mellitus (T2DM) or HbA1c of >6.5 mg/dL at baseline
• Patients diagnosed with or suspected to have a chronic liver disease other than MASLD by screening labs or evaluation (i.e autoimmune, viral). Screening labs are defined as: Hepatitis B surface antigen, Hepatitis C virus total antibody, IgG, ceruloplasmin, and alpha 1 antitrypsin phenotype.
• Patients unable to complete MRI or Labs required for the study.
• Current participation in another clinical trial
• Current participation in a weight loss program or obesity treatment program or clinic
• Cancer or history of cancer within 5 years
• Severe illness that required hospitalization in the last 60 days
• Use of medications known to cause liver steatosis (TPN, amiodarone, chronic oral steroids, etc.)
• Patients with implanted metal devices that are not compatible with magnetic resonance imaging (MRI).
• Intellectual disability or major psychiatric disorder limiting informed assent
• Clinical evidence of cirrhosis or advanced liver disease by any one of the following abnormal labs: (Hemoglobin less than 10 g/dL, White blood cell less than 3,500 cells/mm, Neutrophil count less than 1,500 cells/mm3 of blood, Platelets less than 130,000 cells/mm3 of blood, Direct bilirubin greater than 1.0 mg/dL)
• Elevated total bilirubin except if known to have Gilbert's syndrome and direct bilirubin in normal range.
• Albumin less than 3.2 g/dL
• A history of international normalized ratio (INR) greater than 1.4
• AST or ALT greater than 250 IU/dL.
• Compensated or decompensated cirrhosis with evidence of portal hypertension.
• Patients is pregnant or breastfeeding.
• Patients who have been enrolled in a recent clinical trial and had the last dose of investigational product within 30 days or 5 half-lives of the study drug, whichever is longer.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Corewell Health West — Grand Rapids

Идентификаторы

NCT: NCT07459504 · CHW-2026-1283 · 1R61HL174736-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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