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

Sponsor

Ain Shams University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05613192

Collaborator

(none)

100

Enrollment

Location

Arms

4.1

Anticipated Duration (Months)

24.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease	Drug: Cholecalciferol	Phase 3

Detailed Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Group 1: patients received the standard conventional therapy in addition to placebo for 4 months. Group 2: patients received 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.Group 1: patients received the standard conventional therapy in addition to placebo for 4 months. Group 2: patients received 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.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Study medications were given to the patients by an unblinded pharmacist to ensure the right treatment assignment, however this pharmacist was not included in the outcome assessment. All patients were diagnosed with NAFLD depending on abdominal ultrasonography performed by a radiologist where the liver brightness and liver parenchyma with diffuse echogenicity in confirm the diagnosis.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 31, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 5, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Efficacy of cholecalciferol on glycaemic control parameters in non alcoholic fatty liver disease [at Baseline and at week 16]
Decrease in glycated haemoglobin in NAFLD patients

Secondary Outcome Measures

Efficacy of cholecalciferol on the degree of steatosis in non alcoholic fatty liver disease [at Baseline and at week 16]
Decrease in the degree of steatosis imaged by ultrasonography

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).