Role of Vitagliptin and Vitamin D in the Treatment of Non Alcoholic Fatty Liver Disease (NAFLD)

Study Overview
=================
Brief Summary
-----------------
Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic and increasing the risk for developing nonalcoholic fatty liver disease (NAFLD). The strong relationship between insulin resistance and NAFLD suggests that adding Vitamin D TO insulin sensitizing therapies such as Galvus (vitagliptin) might be beneficial in the prevention or improvement in NAFLD. Considering the close relationship between NAFLD and T2DM and lipid metabolism, we assume that adding vitamin D to Galvus, may be effective for NAFLD by improving lipid metabolism and by improving type 2 diabetes mellitus (T2DM).

Detailed Description
-----------------
Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic and increasing the risk for developing nonalcoholic fatty liver disease (NAFLD). The strong relationship between insulin resistance and NAFLD suggests that adding vitamin D to insulin sensitizing therapies such as Galvus (vitagliptin) might be beneficial in the prevention or improvement in NAFLD. Considering the close relationship between NAFLD and T2DM and lipid metabolism, we assume that adding vitamin D to Galvus may be effective for NAFLD by improving lipid metabolism and by improving T2DM. Methods: 60 patients with NAFLD (Diagnosed by Ultrasound, increase ALT level and hepatomegaly) will be enrolled, and divided into 2 arms Galvus plus Vitamin D vs. Galvus alone. Biochemistry, hepatic triglycerides, histology, m RNA gene expression of collagen, MTP, SREP-1, PPAR-alpha, and LDLR will be measured. 2 separate liver biopsies will be performed at screening and 6 months from baseline. Expected results: Long-term combination therapy with vitagliptin and Vitamin D significantly reduced steatosis, inflammation and fibrosis in the liver compared with long-term monotherapy. We expect also that the combination therapy also significantly increased the expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferators-activated receptor-α1 (PPAR-α1) in the liver, compared with monotherapy, which may have lead to the improvement in lipid metabolic disorder . Conclusion: Combination therapy of vitagliptin and vitamin D, for 24 weeks improve the histopathology findings in NAFLD.

Official Title
-----------------
Role of Vitagliptin and Vitamin D in the Treatment of Non Alcoholic Fatty Liver Disease (NAFLD)

Conditions
-----------------
Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
-----------------
* Drug: Galvus (vitagliptin)
* Drug: Galvus + vitamin D


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-65 years old Men and women with NAFLD per US Increased ALT level Hepatomegaly Liver biopsy within 2 years Exclusion Criteria: Other liver diseases (HBV, HCV) Hepatocellular carcinoma Decompensated liver disease Use of steroids

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Galvus + vitamin D<br>Galvus in combination with vitamin D | Drug: Galvus + vitamin D<br>* Galvus + vitamin D<br>|
| Other: Galvus<br>vitagliptin as monotherapy | Drug: Galvus (vitagliptin)<br>* Galvus (vitagliptin)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| decrease in histological findings | decrease in histological findings: decrease in fat concentration and fibrosis degree | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NAFLD, Galvus, vitamin D