Clinical trial NCT06843148: 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).
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
Liver Fibrosis/NASH
Non-Alcoholic Steato-Hepatitis (NASH)
Keywords: Fatty liver
Niacin
vitamin B3
nicotinic acid
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: Centre hospitalier universitaire de Québec- Université Laval
name: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
First posted: 2025-02-24
Enrollment: 36
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Prolonged small-dose niacin treatment does not lead to desensitization of the niacin-induced reduction in hepatic total fatty acids flux.
timeFrame: Week 12, Week 28
Secondary outcomes:
measure: Change in White Adipose Tissue (WAT) and lean tissue Dietary Fatty Acid (DFA) uptake
timeFrame: Week 12, Week 28
measure: Change in total hepatic fatty acid flux
timeFrame: Week 12, Week 28
measure: Change in hepatic Non-Esterified-Fatty-Acid (NEFA) uptake oxidation, esterification and secretion into very low-density lipoprotein (VLDL)
timeFrame: Week 12, Week 28
measure: Change in Endogenous Glucose production and meal glucose systemic flux
timeFrame: Week 12, Week 28
measure: Change in plasma NEFA flux
timeFrame: Week 12, Week 28
measure: Change in hepatic Triglyceride (TG) content
timeFrame: Week 12, Week 28
measure: Change in insulin secretion
timeFrame: Week 12, Week 28
measure: Change in hormonal response
timeFrame: Week 12, Week 28
measure: Change in metabolite response
timeFrame: Week 12, Week 28
measure: Change in plasma distribution of DFA metabolites
timeFrame: Week 12, Week 28
measure: Change in glycerol turnover
timeFrame: Week 12, Week 28
measure: Change in total substrate utilisation
timeFrame: Week 12, Week 28
measure: Change in insulin resistance /sensitivity
timeFrame: Week 12, Week 28
measure: Circulating markers of hepatic inflammation
timeFrame: Week1, Week 12, Week 16, Week 28
measure: Adverse events
timeFrame: up to 28 weeks
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Centre de recherche du CHUS
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: André Carpentier, MD
role: PRINCIPAL_INVESTIGATOR
References: