Vitamin D in Fatty Liver Disease

Use of Vitamin D in Treatment of Non-Alcoholic Fatty Liver Disease Detected by Transient Elastography

This study evaluates the influence of vitamin D in reducing laboratory, elastographic (Fibroscan) and metabolic components of NAFLD. Half of the patients will receive vitamin D (Plivit D3) while the other half will receive placebo

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency; Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: 1,25-Dihydroxyvitamin D; Drug: Placebo

Detailed Description

In this study will participate patients who come to the regular ambulatory examinations (referred by gastroenterologists, or family physicians in the Department of Gastroenterology CHC Rijeka) and have one or more components of the metabolic syndrome (hypertension, diabetes, obesity, dyslipidemia).Nonalcoholic fatty liver disease will be defined by transient elastography (FibroScan, Echosens, Paris); Controlled Attenuation Parameter (CAP) for assesment of liver steatosis and Liver Stiffness Measurements (LSM) for liver fibrosis. In all patients other causes of chronic liver disease will be excluded; chronic viral hepatitis, autoimmune diseases and other metabolic liver diseases as well as use of drugs than can cause liver steatosis and fibrosis and alcoholic liver disease.

This study will include 450 patients. Taking into account the possible drop-out rate around 15% of the patients during the study period, a total of 400 patients will be randomized. Patients will be randomized into two groups. The first group will be consisted of the patients with NAFLD who will be receiving original medication during the 12 month period. The second group will be consisted of the patients with NAFLD who will be receiving placebo during the 12 months period, which will be identical to the original medication in its packaging and form.

After the 6 and 12 months of therapy in all patients will be evaluated: liver enzymes and metabolic laboratory parameters of NAFLD (insulin resistance, lipidogram and serum glucose), as well as the TE-CAP in order to evaluate the efficiency of Plivit D3 for the treatment of NAFLD.

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with Non-Alcoholic Fatty Liver Disease (NAFLD)
• signed informed consent
• possibility to follow instruction and the protocol

Exclusion Criteria:

• chronic B or C hepatitis
• usage of hepatotoxic drugs in the period of 6 months before inclusion
• chronic kidney insufficiency (grade 4 and 5), hemodialysis
• any other chronic liver disease
• opioid dependancy
• any malignancy
• HIV seropositivity
• alcohol abuse
• pregnancy
• inability to follow the protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D; Intervention drug, containing 1,25-dihydroxy-vitamin D, comes in original packages as vials containing a total amount of 10 ml of clear solution. 5 drops accounting for 1000 IU of 1,25-dihydroxy-vitamin D will be administered orally on a daily basis.	Drug: 1,25-Dihydroxyvitamin D; 1,25-dihydroxy-vitamin D3 1000 IU orally daily for 12 months; Other Names: 1,25-Dihydroxy-Cholecalciferol, Cholecalciferol, Vitamin D3
Placebo Comparator: Placebo; A placebo identical to the study intervention drug in all its characteristics (package, visual characteristics of the fluid, smell, and taste) will be administered in the same manner.	Drug: Placebo; Placebo identical to the study intervention drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elastographic parameter of steatosis	Change of elastographic parameter of steatosis (Controlled Attenuation Parameter; CAP) during the 6 and 12 months period	Week 0 - initiation; after 6 months; and after 12 months (end of study)
Elastographic parameter of fibrosis	Change of elastographic parameter of fibrosis (liver stiffness measurements; LSM) during the 6 and 12 months period	Week 0 - initiation; after 6 months; and after 12 months (end of study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aspartate transaminase	Change in liver enzyme aspartate transaminase (AST) serum levels in the period of 6 and 12 months. Normal range = 11-38 IU/L.	Week 0 - initiation; after 6 months; and after 12 months (end of study)
Alanine transaminase	Change in liver enzyme alanine transaminase (ALT) serum levels in the period of 6 and 12 months. Normal range = 12-48 IU/L.	Week 0 - initiation; after 6 months; and after 12 months (end of study)
Gamma-glutamyl transferase	Change in liver enzyme gamma-glutamyl transferase (GGT) serum levels in the period of 6 and 12 months. Normal range = 11-55 IU/L.	Week 0 - initiation; after 6 months; and after 12 months (end of study)
Insuline Resistance	Change in insulin resistance defined by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; normal range = 0.5 to 1.4) score in the period of 6 and 12 months	Week 0 - initiation; after 6 months; and after 12 months (end of study)
Total cholesterol	Change in total cholesterol serum levels in the period of 6 and 12 months	Week 0 - initiation; after 6 months; and after 12 months (end of study)
Low-density lipoprotein	Change in low-density lipoprotein (LDL) serum levels in the period of 6 and 12 months	Week 0 - initiation; after 6 months; and after 12 months (end of study)
High-density lipoprotein	Change in high-density lipoprotein (HDL) serum levels in the period of 6 and 12 months	Week 0 - initiation; after 6 months; and after 12 months (end of study)
Triglyceride	Change in triglyceride (TG) serum levels in the period of 6 and 12 months	Week 0 - initiation; after 6 months; and after 12 months (end of study)

Collaborators and Investigators

• Sponsor: University Hospital Rijeka
• Collaborators: University of Rijeka; Pliva Hrvatska d.o.o.
• Investigators: Principal Investigator: Ivana Mikolasevic, MD, PhD, Department of Gastroenterology, Clinical Hospital Center Rijeka, University of Rijeka, Croatia

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 28, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 28, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Liver Diseases; Fatty Liver; Vitamin D Deficiency; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Vitamin D; Cholecalciferol; Calcitriol; Dihydroxycholecalciferols
• Other Study ID Numbers: 00000000-NAFLD

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
• product manufactured in and exported from the U.S.: No