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

Not Applicable

Not yet recruiting

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

• Registration Number: NCT06843148
• Lead Sponsor: Université de Sherbrooke

Brief Summary

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

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 Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-02-12
• Study First Submitted QC: 2025-02-18
• Last Update Submitted: 2025-02-18
• Study First Posted: 2025-02-24
• Last Update Posted: 2025-02-24
• Study Start: 2025-04
• Primary Completion: 2030-03
• Study Completion: 2030-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 36

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo group	Placebo Oral Tablet	It will be a 12-week treatment phase. The placebo treatment will be administered once daily, at the end of the largest meal.
Niacin group	Niacin (250mg)	It will be a 12-week treatment phase. The treatment will be administered once daily, at the end of the largest meal.

Primary Outcome Measures

Name	Time	Method
Prolonged small-dose niacin treatment does not lead to desensitization of the niacin-induced reduction in hepatic total fatty acids flux.	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Centre de recherche du CHUS; 🇨🇦 Sherbrooke, Quebec, Canada