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 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
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
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:
- 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 \[106-109\].
- Other hepatic disease.
- Previous diagnosis of diabetes.
- Overt cardiovascular or renal disease, cancer (other than non-melanoma skin cancer), or other uncontrolled medical conditions.
- Any contraindication to MRI.
- Previous intolerance or allergy to nicotinic acid.
- Having participated to a research study with exposure to radiation in the last two years before the start of the study.
- Being allergic to eggs
- Smoking (\>1 cigarette/day) and/or consumption of \>2 alcoholic beverages per day.
