Vitamin D in Fatty Liver Disease

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Non-alcoholic Fatty Liver Disease, Vitamin D Deficiency

Intervention / Treatment
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* Drug: 1,25-Dihydroxyvitamin D
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D<br>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<br>* 1,25-dihydroxy-vitamin D3 1000 IU orally daily for 12 months<br>* Other names: 1,25-Dihydroxy-Cholecalciferol, Cholecalciferol, Vitamin D3;|
| Placebo Comparator: Placebo<br>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<br>* Placebo identical to the study intervention drug<br>|

What is the study measuring?
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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) |