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

NCT ID: NCT02242149

Last Updated: 2018-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-14
• Study Completion Date: 2018-01-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sugar pill manufactured to mimic 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.

Group Type: EXPERIMENTAL

Diacerein

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Placebo

Sugar pill manufactured to mimic Diacerein

Intervention Type: DRUG

Other Intervention Names

Artrodar; Artifit; Acert

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rio de Janeiro State Research Supporting Foundation (FAPERJ)

OTHER_GOV

Sponsor Role: collaborator

Universidade Federal do Rio de Janeiro

OTHER

Sponsor Role: lead

Responsible Party

Gil Fernando da Costa Mendes de Salles, PhD

Full Professor, Faculty of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gil F Salles, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidade Federal do Rio de Janeiro

Locations

Program of Arterial Hypertension, University Hospital Clementino Fraga Filho

Rio de Janeiro, , Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 28818994 (View on PubMed)

Other Identifiers

30194914.3.0000.5257

Identifier Type: -

Identifier Source: org_study_id