Stimulating Fat Tissue Storage With Niacin to Reduce Fat Accumulation in the Liver. (AGL13)

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

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 50 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

Study Overview

• Status: Recruiting
• Conditions: Non-Alcoholic Steato-Hepatitis (NASH); Liver Fibrosis/NASH; Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Niacin (250mg)

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Frédérique Frisch; Phone Number: 12394 1-819-346-1110; Email: frederique.frisch@usherbrooke.ca

Study Locations

• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Recruiting
      • Centre de Recherche du CHUS
      • Contact: Frédérique Frisch; Phone Number: 12394 1-819-346-1110; Email: frederique.frisch@usherbrooke.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• aged 50 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;
• all women will be post-menopausal.

Exclusion Criteria:

1. Presence of advanced fibrosis (i.e., ≥ F3 based on liver stiffness > 10kPa) using vibration-controlled transient elastography (FibroScan), serum ALT > 3 times the normal upper limit, or signs of portal hypertension [106-109].
2. Other hepatic disease.
3. Previous diagnosis of diabetes.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	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)
Active Comparator: Niacin group; It will be a 12-week treatment phase. The treatment will be administered once daily, at the end of the largest meal.	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); Other Names: Vitamin B3; Nicotinic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolonged small-dose niacin treatment does not lead to desensitization of the niacin-induced reduction in hepatic total fatty acids flux.	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.	Week 12, Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in White Adipose Tissue (WAT) and lean tissue Dietary Fatty Acid (DFA) uptake	Determined from the same static (whole-body) acquisition image using oral administration of [18F]-Fluoro-6-Thia-Heptadecanoic Acid (FTHA)	Week 12, Week 28
Change in total hepatic fatty acid flux	represents the sum of the rate of NEFA uptake and DFA uptake (PET scan using [18F]-FTHA and [11C]-palmitate	Week 12, Week 28
Change in hepatic Non-Esterified-Fatty-Acid (NEFA) uptake oxidation, esterification and secretion into very low-density lipoprotein (VLDL)	[11C]-Palmitate PET. Calculated from the same multicompartmental equation using liver [11C]-palmitate kinetics	Week 12, Week 28
Change in Endogenous Glucose production and meal glucose systemic flux	i.v. and oral stable isotope tracer	Week 12, Week 28
Change in plasma NEFA flux	calculated from i.v. stable isotope tracer (mass spectrometry).	Week 12, Week 28
Change in hepatic Triglyceride (TG) content	magnetic resonance imaging (MRI)	Week 12, Week 28
Change in insulin secretion	Determined by measuring C-peptide kinetics following the liquid meal	Week 12, Week 28
Change in hormonal response	Multiplex assay	Week 12, Week 28
Change in metabolite response	Colorimetric assay	Week 12, Week 28
Change in plasma distribution of DFA metabolites	calculated from i.v. and oral stable isotope tracers (mass spectrometry) incorporated into triglyceride-rich lipoproteins and NEFA.	Week 12, Week 28
Change in glycerol turnover	calculated from [1,1,2,3,3-2H]-glycerol i.v.	Week 12, Week 28
Change in total substrate utilisation	measured by using indirect calorimetry	Week 12, Week 28
Change in insulin resistance /sensitivity	Determined by measuring circulating glucose, NEFA and insulin following the liquid meal.	Week 12, Week 28
Circulating markers of hepatic inflammation	Measurement of Alanine aminotransferase (ALT), Aspartate transaminase (AST) and platelet count for calculation of fibrosis-4 which is an index for liver fibrosis.	Week1, Week 12, Week 16, Week 28
Adverse events		up to 28 weeks

Collaborators and Investigators

• Sponsor: Université de Sherbrooke
• Collaborators: Centre de recherche du Centre hospitalier universitaire de Sherbrooke; Centre hospitalier universitaire de Québec- Université Laval
• Investigators: Principal Investigator: André Carpentier, MD, Universite de Sherbrooke

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: February 12, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Niacin; Fatty liver; nicotinic acid; vitamin B3
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acids, Heterocyclic; Nicotinic Acids; Niacin; Niacinamide
• Other Study ID Numbers: 2025-5648

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No