A Sequential Multiple Assignment Randomized Trial of Diet Treatments for Hepatic Steatosis and Cardiometabolic Risk in Youth
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Change in hepatic steatosis
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Due to the nature of the treatment, it is not realistic to blind the treatment to either staff or patients and their caregivers. To mitigate the risk of bias associated with an unblinded study, all study team members will remain blinded to aggregate study results and only select members of the study team responsible for interim monitoring will have access to these data
入排标准
- 年龄范围
- 11 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Essential Amino Acids Supplementation
The essential amino acid supplement contains the following formulation: histidine, isoleucine, leucine, lysine, phenylalanine, threonine, and valine. EAA, also called AMS2392 has been shown to decrease hepatic steatosis and lower circulating very-low-density lipoprotein triglyceride (VLDL-TG) concentrations through one or more of the following mechanisms: decreasing de novo lipogenesis; increasing hepatic and systemic fatty acid oxidation; increasing triglyceride secretion from the liver in the form of VLDL-TG; and increasing clearance of circulating VLDL-TG via activation of lipoprotein lipase.
干预措施: Essential Amino Acids Supplementation intervention (Drug)
Low Sugar Diet
The Low Sugar Diet uses the adapted and extended Social Cognitive Theory (SCT) guided low sugar intervention that the Emory team previously developed. 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.
干预措施: Low sugar diet (Other)
结局指标
主要结局
Change in hepatic steatosis
时间窗: Baseline to 24 weeks
Change in hepatic steatosis by magnetic resonance imaging (MRI)
次要结局
- Change in fasting triglyceride(Baseline, 12 and 24 weeks)
- Change in HDL(Baseline, 12 and 24 weeks)
- Change in VLDL-triglyceride(Baseline, 12 and 24 weeks)
- Change in Waist circumference(Baseline, 12 and 24 weeks)
- Change in body weight(Baseline, 12 and 24 weeks)
- Change in BMI Z Score(Baseline, 12 and 24 weeks)
- Change in Alanine Aminotransferase (ALT)(Baseline, 12 and 24 weeks)
- Aspartate Aminotransferase (AST)(Baseline, 12 and 24 weeks)
- Gamma glutamyl transferase (GGT)(Baseline, 12 and 24 weeks)
- Systolic blood pressure(Baseline, 12 and 24 weeks)
- Diastolic blood pressure(Baseline, 12 and 24 weeks)
- Hemoglobin A1c(Baseline, 12 and 24 weeks)
- HOMA-IR(Baseline, 12 and 24 weeks)
- Adverse events(Baseline, 12 and 24 weeks)
- Percent responders(Baseline to 24 weeks)
研究者
Miriam B. Vos
Principal Investigator
Michigan State University