Stimulating Adipose Tissue Fatty Acid Disposal With Low-dose, Postprandial, Intermittent Niacin for the Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD).
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Prolonged small-dose niacin treatment does not lead to desensitization of the niacin-induced reduction in hepatic total fatty acids flux.
研究概览
简要总结
Metabolic dysfunction-associated steatotic liver disease (MASLD) (aka non-alcoholic fatty liver disease), commonly occurring in individuals with obesity and type 2 diabetes can lead to liver inflammation/ fibrosis. MASLD results from fat being disproportionately deposited in the liver.
The goal of this mechanistic study is to investigate metabolic response in patients aged 20 to 80 years with non-alcoholic fatty liver disease, after niacin (vitamin B3) treatment.
The main questions it aims to answer are:
- Does Niacin lower the fat deposition in the liver?
- Does Niacin raise White Adipose Tissue storage of dietary fatty acids?
Researchers will compare Niacin to a placebo (a look-alike substance that contains no drug) to compare the metabolic response.
Duration of study per participant: Up to 28 weeks
详细描述
It will be a randomized crossover study with two 12-week treatment phases (niacin vs. placebo) with a 4-week washout period between the two treatment phases.
The two 12-week treatment phases will be performed in random order. The treatment will be administered once daily, at the end of the largest meal. There will be a 3-week dose escalation: from 250mg (the first week) to 750mg from week 3 onward.
The outcomes will be assessed at the end of each of these two treatment phases in all participants with metabolic visit A and B (i.e., a total of 4 metabolic visits).
Each metabolic visit will last 9 hours: it will be a test meal with perfusion of stable tracers, blood sampling, PET acquisitions using radiopharmaceuticals (18FTHA and 11C-palmitate) and MRI acquisitions.
The two visits A and B will be performed without and with acute administration of niacin with the test meal, respectively, to determine acute niacin-induced reduction in hepatic fatty acid flux.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •aged 20 to 80 years;
- •diagnosed with MASLD, defined as the presence of liver steatosis + abdominal obesity (as defined by the International Diabetes Federation country/ethnic group-specific criteria;
排除标准
- •1) Presence of advanced fibrosis using any of the following criteria 1.1 (i.e., ≥ F3 based on liver stiffness > 10kPa) using vibration-controlled transient elastography (FibroScan), 1.2 (Index for Liver Fibrosis > 2.67) using Fibrosis-4 (FIB-4) which is a calculated score based on age and a combination of lab tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and platelet count), 1.3 serum ALT > 3 times the normal upper limit, 1.4 or signs of portal hypertension. 2) Other hepatic disease. 4) Overt cardiovascular or renal disease, cancer (other than non-melanoma skin cancer), or other uncontrolled medical conditions.
- •5) Any contraindication to MRI. 6) Previous intolerance or allergy to nicotinic acid. 7) Having participated to a research study with exposure to radiation in the last two years before the start of the study.
- •8) Being allergic to eggs 9) Smoking (>1 cigarette/day) and/or consumption of >2 alcoholic beverages per day.
- •10) Women who are pregnant or breastfeeding.
研究组 & 干预措施
Placebo group
It will be a 12-week treatment phase. The placebo treatment will be administered once daily, at the end of the largest meal.
干预措施: Placebo Oral Tablet (Drug)
Niacin group
It will be a 12-week treatment phase. The treatment will be administered once daily, at the end of the largest meal.
干预措施: Niacin (250mg) (Drug)
结局指标
主要结局
Prolonged small-dose niacin treatment does not lead to desensitization of the niacin-induced reduction in hepatic total fatty acids flux.
时间窗: Week 12, Week 28
Total 6 h integrated uptake of circulating NEFAs, DFAs, and all FAs in liver: represents the sum of the rate of NEFA uptake integrated over 360 min for the entire organ and the rate of DFA uptake integrated over 360 min for the entire organ.
次要结局
- Change in White Adipose Tissue (WAT) and lean tissue Dietary Fatty Acid (DFA) uptake(Week 12, Week 28)
- Change in total hepatic fatty acid flux(Week 12, Week 28)
- Change in hepatic Non-Esterified-Fatty-Acid (NEFA) uptake oxidation, esterification and secretion into very low-density lipoprotein (VLDL)(Week 12, Week 28)
- Change in Endogenous Glucose production and meal glucose systemic flux(Week 12, Week 28)
- Change in plasma NEFA flux(Week 12, Week 28)
- Change in hepatic Triglyceride (TG) content(Week 12, Week 28)
- Change in insulin secretion(Week 12, Week 28)
- Change in hormonal response(Week 12, Week 28)
- Change in metabolite response(Week 12, Week 28)
- Change in plasma distribution of DFA metabolites(Week 12, Week 28)
- Change in glycerol turnover(Week 12, Week 28)
- Change in total substrate utilisation(Week 12, Week 28)
- Change in insulin resistance /sensitivity(Week 12, Week 28)
- Circulating markers of hepatic inflammation(Week1, Week 12, Week 16, Week 28)
- Adverse events(up to 28 weeks)
研究者
André Carpentier
Tenure professor
Université de Sherbrooke