Efficacy Study of Diacerein on Glycemic Control and Liver Fat in Type 2 Diabetes Subjects

Study Overview
=================
Brief Summary
-----------------
This study is conducted to test the hypothesis that in uncontrolled type 2 diabetic adults treatment with diacerein will improve glycemic control and will reduce liver fat within a 24 month period.

Detailed Description
-----------------
Background: Recently, knowledge about diacerhein, an anthraquinone drug with powerful anti-inflammatory properties, revealed that this drug improves insulin sensitivity, mediated by the reversal of chronic subclinical inflammation. Amongst the numerous pathogenetic factors, oxidative stress and apoptosis of hepatocytes initiate many inflammatory processes and are involved in the progression of Non alcoholic fatty liver disease. Aims:The aim is to evaluate the effect of treatment with diacerein in improvement of glycemic parameters (mean glycated hemoglobin, fasting blood sugar) and reduction of liver fat fraction. Methods:Two-hundred patients will be randomly allocated either to treatment with diacerein plus their usual therapeutic regimen or to placebo for 24 months. Clinic, laboratory evaluation (including glycated hemoglobin, fasting blood sugar, creatinine, ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), g-glutamyl transpeptidase, alkaline phosphatase, bilirubin, albumin, prothrombin time, platelet count, total cholesterol, high-density and low-density lipoprotein cholesterol and triglycerides and urinary albumin excretion rate no 24-hour urine collection) will be performed before and every 3 months until the end of study. Pro-Inflammatory cytokines, adiponectin and cytokeratin-18 were measured before, at 12 months and at the end of study. Liver fat fraction measurement using controlled attenuation parameter (CAP) by transient elastography. (Fibroscan) will be performed before and after the 12 and 24-month treatment, with the observers blinded to the allocation group.

Official Title
-----------------
Efficacy Study of Diacerein on Glycemic Control and Liver Fat in Type 2 Diabetes Subjects

Conditions
-----------------
Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease

Intervention / Treatment
-----------------
* Drug: Diacerein
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 diabetes. Presence of liver steatosis diagnosed by ultrasound or transient elastography (Fibroscan®) Age 30-75 years. HbA1c 7.5- 9.5 for at least 8 weeks prior to screening. Stable diabetes therapeutic regimen consisting of either diet, oral hypoglycemic agents with or without insulin for 8 weeks prior to randomization. Exclusion Criteria: Body mass index > 40 kg/m2 Serum creatinine ≥180mmol/L or estimated glomerular filtration rate < 30 ml/min. Presence of any serious concomitant disease, such as a pulmonary disease or malignant disorders. Current daily alcohol ingestion ≥20 g. Hepatotoxic drugs. Presence of other chronic liver disease other than nonalcoholic fatty liver disease, including hepatitis B virus and hepatitis C virus infection, hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, autoimmune hepatitis. Women seeking pregnancy. Current use or previous use within 6 months of vitamin E or pioglitazone

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>All subjects will be given placebo identically matched with regard to shape, color and taste. They will be given one tablet/day for 2 weeks and then two tablets/day for the duration of sudy. | Drug: Placebo<br>* Sugar pill manufactured to mimic Diacerein<br>|
| Experimental: Diacerein<br>All subjects will be given diacerein with a starting dose of 50 mg in one tablet once daily for 2 weeks. After 2 weeks, they will be given diacerein 50 mg in one tablet twice daily for the duration of sudy. | Drug: Diacerein<br>* All subjects will be given diacerein with a starting dose of 50 mg in one tablet once daily for 2 weeks. After 2 weeks, they will be given diacerein 50 mg in one tablet twice daily for the duration of sudy.<br>* Other names: Acert;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of improvement in glycemic control and improvement in liver steatosis | Reduction of mean glycated hemoglobin (≥ 1%) and reduction of liver fat fraction as measured by transient elastography (≥ 20%) | Within 12 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of microalbuminuria | Reduction of albumin excretion rate on 24-hour urine collection | Within 24 months | 
| Changes of adipocytokines and cytokeratin-18 | Elevation of high molecular weight adiponectin and reduction of the apoptotic by-product cytokeratin (CK)-18 | Within 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fat liver, Diabetes, Diacerein, Transient elastography, Treatment