Clinical trial NCT02242149: Efficacy Study of Diacerein on Glycemic Control and Liver Fat in Type 2 Diabetes Subjects
Official title: Efficacy Study of Diacerein on Glycemic Control and Liver Fat in Type 2 Diabetes Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Non-alcoholic Fatty Liver Disease
Keywords: Fat liver
Diabetes
Diacerein
Transient elastography
Treatment
Lead sponsor: Universidade Federal do Rio de Janeiro
Sponsor class: OTHER
Collaborators: name: Rio de Janeiro State Research Supporting Foundation (FAPERJ)
First posted: 2014-09-16
Enrollment: 84
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Evidence of improvement in glycemic control and improvement in liver steatosis
timeFrame: Within 12 and 24 months
Secondary outcomes:
measure: Improvement of microalbuminuria
timeFrame: Within 24 months
measure: Changes of adipocytokines and cytokeratin-18
timeFrame: Within 24 months
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Program of Arterial Hypertension, University Hospital Clementino Fraga Filho
Study officials:
affiliation: Universidade Federal do Rio de Janeiro
name: Gil F Salles, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cardoso CRL, Leite NC, Carlos FO, Loureiro AA, Viegas BB, Salles GF. Efficacy and Safety of Diacerein in Patients With Inadequately Controlled Type 2 Diabetes: A Randomized Controlled Trial. Diabetes Care. 2017 Oct;40(10):1356-1363. doi: 10.2337/dc17-0374. Epub 2017 Aug 17.