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

Official title

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

Overview

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

Detailed description

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.

Interventions

• Drug 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)
• Drug 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)

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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;

Exclusion criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Basic science

Study locations

Canada · 1 center

• Centre de recherche du CHUS — Sherbrooke

Identifiers

NCT: NCT06843148 · 2025-5648

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗