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

Phase 3

Completed

• Conditions: Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease
• Interventions: Drug: Diacerein; Drug: Placebo

• Registration Number: NCT02242149
• Lead Sponsor: Universidade Federal do Rio de Janeiro

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.

Study Timeline

• Study First Submitted: 2014-09-14
• Study First Submitted QC: 2014-09-15
• Study First Posted: 2014-09-16
• Study Start: 2014-10-14
• Primary Completion: 2017-01-31
• Study Completion: 2018-01-31
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-02
• Last Update Posted: 2018-05-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Diacerein	Diacerein	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.
Placebo	Placebo	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Program of Arterial Hypertension, University Hospital Clementino Fraga Filho; 🇧🇷 Rio de Janeiro, Brazil