Stimulating Fat Tissue Storage With Niacin to Reduce Fat Accumulation in the Liver.

Официальное название

Stimulating Adipose Tissue Fatty Acid Disposal With Low-dose, Postprandial, Intermittent Niacin for the Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD).

Обзор

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

Подробное описание

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.

The two visits will be performed at four to seven-day interval, in random order during the last week of each of the treatment phase.

Вмешательства

• Препарат Niacin (250mg)
  Niacin will be orally taken once daily with the largest meal. There will be a 3-week escalation period from 250 mg to 750 mg: * Week 1: 250mg * Week 2: 500mg * Week 3 to Week 12: 750mg (3 x 250mg caplets)
• Препарат Placebo Oral Tablet
  Placebo will be orally taken once daily with the largest meal. There will be a 3-week escalation period from 250 mg to 750 mg: * Week 1: 250mg * Week 2: 500mg * Week 3 to Week 12: 750mg (3 x 250mg caplets)

Первичные конечные точки

• Prolonged small-dose niacin treatment does not lead to desensitization of the niacin-induced reduction in hepatic total fatty acids flux. [Срок оценки: Week 12, Week 28]

Вторичные конечные точки (12)

• Change in White Adipose Tissue (WAT) and lean tissue Dietary Fatty Acid (DFA) uptake [Срок оценки: Week 12, Week 28]
• Change in total hepatic fatty acid flux [Срок оценки: Week 12, Week 28]
• Change in hepatic Non-Esterified-Fatty-Acid (NEFA) uptake oxidation, esterification and secretion into very low-density lipoprotein (VLDL) [Срок оценки: Week 12, Week 28]
• Change in Endogenous Glucose production and meal glucose systemic flux [Срок оценки: Week 12, Week 28]
• Change in plasma NEFA flux [Срок оценки: Week 12, Week 28]
• Change in hepatic Triglyceride (TG) content [Срок оценки: Week 12, Week 28]
• Change in insulin secretion [Срок оценки: Week 12, Week 28]
• Change in hormonal response [Срок оценки: Week 12, Week 28]
• Change in metabolite response [Срок оценки: Week 12, Week 28]
• Change in plasma distribution of DFA metabolites [Срок оценки: Week 12, Week 28]
• Change in glycerol turnover [Срок оценки: Week 12, Week 28]
• Change in total substrate utilisation [Срок оценки: Week 12, Week 28]

Критерии участия

Критерии включения

• 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;

Критерии исключения

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.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Канада · 1 центр

• Centre de recherche du CHUS — Sherbrooke

Идентификаторы

NCT: NCT06843148 · 2025-5648

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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