The objective of this clinical trial, a pilot study, is to assess the impact of nicotinamide (NAM) on individuals with hepatic fibrosis. The main question it aims to answer is: \- To determine if the treatment with NAM is able to arrest, or even reduce, the hepatic fibrosis. In addition, we also want to study the effect of NAM on: * General parameters (weight, HOMA-IR, etc). * Adiposity distribution (liver and body). * Systemic inflammation. * Thermogenic capacity of adipose tissue. * Microbiota composition. Researchers will compare NAM to a placebo, to see if NAM can arrest or revert hepatic fibrosis and its associated effects. Participants will take either NAM or placebo. The dosage will be 1.2g/m2 NAM per day, for one year.
Patients with a Fibroscan \> 8 kPa will be offered to participate in this study. Participants will receive either placebo or a NAM dose adjusted to body weight. The duration of the treatment is 12 months. Participants will be subjected to a total of 5 follow-up and/or control visits: Visit 1 * Physical examination(weight, height, BMI, waist circumference, neck circumference, blood pressure, and heart rate). * Assessment of muscle status and risk of sarcopenia: grip strength, chair test. * Basal electrocardiogram. * Blood analysis. * Bioelectrical impedance analysis. * Nuclear magnetic resonance. * Thermographic image. * Food questionnaire (PREDIMED). * International Physical Activity Questionnaire (IPAQ). * Collection of blood, urine, and feces samples for storage in the biobank. Visit 2. Control visit (time month 1) * Monitoring of adverse events (AE) and adverse reactions (AR). * Electrocardiogram. * Control blood analysis: sodium, potassium, liver biochemistry (AST, ALT, bilirubin, GGT, FA), renal function (urea, creatinine, estimated glomerular filtration), and coagulation tests. * Physical examination and measurement of vital signs. Visit 3. Follow-up visit (time month 3) * Monitoring of AE and AR. * Drug adherence questionnaire. * Electrocardiogram. * Blood analysis. * Physical examination (weight, BMI, waist circumference, neck circumference, blood pressure, and heart rate). * Collection of blood, urine, and feces samples for biobank. * Collection of concomitant medication. * Adherence to study treatment and dietary recommendations. Visit 4. Follow-up visit (time month 6) * Monitoring of AE and AR. * Drug adherence questionnaire. * Electrocardiogram. * Blood analysis. * Physical examination (weight, BMI, waist circumference, neck circumference, blood pressure, and heart rate). * Collection of blood, urine, and feces samples for biobank. * Collection of concomitant medication. * Adherence to study treatment and dietary recommendations. Visit 5. Control visit (time month 9). * Monitoring of AE and AR. * Drug adherence questionnaire. * Electrocardiogram. * Control blood analysis. * Physical examination. * Collection of concomitant medication. Visit 6. Final exploration (time month 12) * Monitoring of AE and AR. * Drug adherence questionnaire. * Food questionnaire (PREDIMED). * Physical Activity Questionnaire (IPAQ). * Physical examination and measurement of vital signs (weight, BMI, waist circumference, neck circumference, blood pressure, and heart rate). * Assessment of muscle status and risk of sarcopenia: FPM, chair test. * Electrocardiogram. * Blood analysis. * Measurement of NAM and derived metabolites in serum and urine. * Nuclear magnetic resonance. * Bioimpedance. * Thermographic image. * Fibroscan® with CAP. * Collection of blood, urine, and feces samples for biobank The safety of the participants will be assessed using a record of the AEs and ARs that could arise and their annotation in the EDC, as well as a regular evaluation of liver, kidney, and heart function at baseline, 1, 3, 6, 9 and 12 months
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
Administration of NAM on a variable dose depending on the participant's body weight. Administration is done orally, daily.
Administration of placebo on a variable dose depending on the participant's body weight. Administration is done orally, daily.
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
RECRUITINGEffect of nicotinamide on hepatic fibrosis
Measurement of hepatic fibrosis by Fibroscan, to asses the arrest or improvement of fibrosis (lower value than basal Fibroscan result)
Time frame: Fibroscan at 0 and 12 months.
Effect of nicotinamide on body fat and hepatic fat distribution
Analysis of body and hepatic fat by magnetic ressonance and observe visual differences between the basal and final images
Time frame: 0 and 12 months
Effect of nicotinamide on the general health state (weight)
Analysis of body weight (grams) and waist circumference (cm), a reduction in both would point to a better general status and a weight loss
Time frame: Blood test and strength test at 0, 3, 6, and 12 months
Effect of nicotinamide on the general health state (strenght)
Evaluation of the grip strength as a measure of muscle strength
Time frame: Blood test and strength test at 0, 3, 6, and 12 months
Effect of nicotinamide on the Insulin resistance
Calcutaltion of the HOMA-IR (homeostatic model assessment - Insulin Resistance) index, a reduction of the HOMA-IR index shows a reduction of insulin resistance and an improved glucose metabolism
Time frame: Blood test and strength test at 0, 3, 6, and 12 months
Effect of nicotinamide on gut microbiota
Analyses of the gut microbiota composition during the NAM treatment
Time frame: Test at 0, 3, 6, and 12 months
Effect of nicotinamide on systemic inflammation
Analysis of the evolution of systemic inflammation by ELISA (enzyme-linked immunosorbent assay) of several cytokines related to inflammation. Lower values are usually associated to lower inflammation.
Time frame: Blood test at 0, 3, 6, and 12 months
Effect of nicotinamide on cellular inflammation
Analysis of the evolution of cellular inflammation by analyzing the count and type of peripheral blood mononuclear cells by flow-cytometry
Time frame: Blood test at 0, 3, 6, and 12 months
Security evaluation LIVER
Security evaluation of the dosage of nicotinamide administered by analyzing liver parameters of aspartate transaminase (AST), alanine transaminase (ALT), and coagulation parameters.
Time frame: 0, 1, 3, 6, 9, and 12 months
Security evaluation KIDNEY
Security evaluation of the dosage of nicotinamide administered by measuring glomerular filtrate and creatinine
Time frame: 0, 1, 3, 6, 9, and 12 months
Effect of nicotinamide on liver parameters
Evaluation of the effects of nicotinamide on liver status by ELF-test, to observe if there is any improvement (lower value than basal measurement)
Time frame: 0 and 12 months
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