Effectiveness of Inactive Vitamin D Supplementation in Non-Alcoholic Fatty Liver Disease Patients

The Effect of High Oral Loading Dose of Cholecalciferol in Non-Alcoholic Fatty Liver Disease Patients. A Randomized Placebo Controlled Trial

Aim of work The aim of our study is to assess the effectiveness and safety of high oral loading dose of inactive vitamin D supplementation on the clinical parameters related to liver steatosis, glycaemic control, insulin resistance and metabolic profile in NAFLD patients

Study Overview

• Status: Recruiting
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Cholecalciferol

Detailed Description

Aim of work The aim of our study is to assess the effectiveness and safety of high oral loading dose of inactive vitamin D supplementation on the clinical parameters related to liver steatosis, glycaemic control, insulin resistance and metabolic profile in NAFLD patients

Patients and Methods The present study is prospective, simply (via computer generated sequence) randomized controlled double blinded study, will be conducted on NAFLD patients in the outpatient liver clinics of EL Sahel Teaching hospital, Cairo, Egypt, Inclusion criteria: To be included in the study, patients have to fulfil the following inclusion criteria: male or female patients >19 years of age; presence of fatty liver detected by upper abdominal ultrasound echography (US) and with diagnosis of T2D according to ADA 2019 criteria.

Exclusion Criteria: The main exclusion criteria from the study are as follows: Pregnancy and lactation, history of alcohol abuse (as defined by an average daily consumption of alcohol > 30 g/day in men and > 20 g/day women), cirrhosis, autoimmune hepatitis and other causes of liver disease (viral hepatitis, hemochromatosis, Wilson's disease), drug induced hepatitis, chronic enteropathies, Chronic kidney disease, hyper/hypoparathyroidism, known hypersensitivity to cholecalciferol.

Hundred eligible patients will be included into the study and randomized by simple randomization into either of the 2 groups:

Group 1: 50 patients receive the standard conventional therapy in addition to placebo for 4 months.

Group 2: 50 patients receive the standard conventional therapy in addition to a single oral dose of cholecalciferol 300,000 IU followed by oral cholecalciferol 800 IU daily for 4 months.

The following laboratory tests will be measured: a- Glycaemic control: Fasting blood glucose (FBG mg/dl), glycated haemoglobin (HbA1C%), Fasting insulin (mU/L), Insulin resistance index calculated by the homeostasis model assessment insulin resistance (HOMA-IR) method using the product of fasting insulin and fasting plasma glucose divided by 405. The cut off value of HOMA-IR is more than 1.64.

b-Liver function tests: Alanine transaminase (ALT U/L), Aspartate transaminase (AST U/L), Albumin (g/dl), Gamma glutamyl transferase (GGT U/L), Alkaline phosphatase (ALP U/L).

c- Lipid Profile: Low density lipoprotein (LDL-C mg/dl), High density lipoprotein (HDL-C mg/dl), Triglycerides (TG mg/dl), Total cholesterol (TC mg/dl) d- Other markers: High sensitivity C reactive protein (hsCRP mg/dl), Alfa fetoprotein (AFP ng/ml), serum 25-hydroxy vitamin D (25(OH) D ng/ml) All Patients were followed up every 2 weeks by the clinical pharmacist in charge through patient encounter to ensure the compliance to the treatment regimen and to assess any adverse side effects.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Radwa El Borolossy, phd; Phone Number: 01227052880; Email: radwa.maher14@yahoo.com

Study Locations

• Egypt
  • Cairo, Egypt, 0000
    • Recruiting
    • National Hepatology and Tropical Medicine Research Institute
    • Contact: Radwa El Borolossy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients >18 years with fatty liver diagnosis by using upper abdominal ultrasound echography (US)
• patients with T2D diagnosed according to ADA 2019 criteria and treated with metformin.

Exclusion Criteria:

• Pregnant and/or lactating women,
• excessive alcohol use (as defined by an average daily consumption of alcohol > 30 g/day in men and > 20 g/day women),
• patients with other causes of chronic liver disease as viral hepatitis, drug induced hepatitis, autoimmune hepatitis, patients suffering of chronic kidney disease, hyper/hypoparathyroidism,
• hypersensitivity to cholecalciferol,
• hypercalcemia,
• patients taking supplementation with vitamin D,
• calcium and medications affecting calcium/vitamin D metabolism (as: anticonvulsants, glucocorticoids, antacids).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo; Group 1: patients receive the standard conventional therapy in addition to placebo for 4 months.	Drug: Cholecalciferol; patients receive the standard conventional therapy in addition to a single oral dose of cholecalciferol 300,000 IU followed by oral cholecalciferol 800 IU daily for 4 months.; Other Names: native vitamin D
Experimental: Cholecalciferol; Group 2: patients receive the standard conventional therapy in addition to a single oral dose of cholecalciferol 300,000 IU followed by oral cholecalciferol 800 IU daily for 4 months.	Drug: Cholecalciferol; patients receive the standard conventional therapy in addition to a single oral dose of cholecalciferol 300,000 IU followed by oral cholecalciferol 800 IU daily for 4 months.; Other Names: native vitamin D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of cholecalciferol on glycaemic control parameters in non alcoholic fatty liver disease	Decrease in glycated haemoglobin in NAFLD patients	at Baseline and at week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of cholecalciferol on the degree of steatosis in non alcoholic fatty liver disease	Decrease in the degree of steatosis imaged by ultrasonography	at Baseline and at week 16

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Radwa El Borolossy, faculty of pharmacy Ain Shams university

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 5, 2023

Study Registration Dates

• First Submitted: October 31, 2022
• First Submitted That Met QC Criteria: November 3, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: non-alcoholic fatty liver- vitamin D
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: NHTMRI-IRB 10-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No