Clinical trial NCT03208309: Effect of Diacerein in the Metabolic Control of Patients With DM Type 2 and Secondary Failure to Metformin
Official title: Effect of Diacerein in the Metabolic Control of Patients With Diabetes Mellitus Type 2 and Secondary Failure to Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Complications of Diabetes Mellitus
Diabetes Mellitus
Diabetes Mellitus, Type 2
Lead sponsor: ANS Pharma
Sponsor class: INDUSTRY
Collaborators: name: University of Campinas, Brazil
name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2017-07-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Considering that, Diacerein is on the market for 16 years being used continuously in elderly patients with osteoarthritis without experience significant side effects, and considering the anti-hyperglycemic effect and the improvement in the insulin resistance observed in animal models of type 2 diabetes treated with this medicine.

The aim of this study is to investigate the effect of Diacerein, a medication with anti-osteoarthritic properties and moderately analgesic activity, anti-inflammatory and antipyretic, which demonstrates inhibit properties for the synthesis of pro-inflammatory cytokines such as interleukin 1 (IL-1). Administered for 12 weeks and the effect in the glycemic and metabolic control in patients with diabetes mellitus 2 and secondary failure to metformin treatment.

Detailed description: This proof of concept study aims to access the metabolic control in patients with type 2 diabetes mellitus and secondary failure to metformin.

The Study is a Phase II, Multicenter, National, Prospective, Randomized, Double-blind, Parallel Groups, Placebo Comparative Trial. UNICAMP (Hospital of Unicamp) is the coordinator center and the investigators and research center participating are from the State University of Feira de Santana (BA) and the Center for Diabetes and Hypertension in Fortaleza (CE).

Study Objectives: To investigate the effect of Diacerein administered for 12 weeks; glycemic and metabolic control; in patients with diabetes mellitus type 2 and secondary failure to metformin treatment. The Total Number of patients will be approximately 60, 30 patients in each group.

Diagnostic Criteria - Diabetes mellitus type 2 between 6 months to 10 years of disease, body mass index between 25 and 35 kg/m2, fasting glucose between 120 and 250 mg / dL, glycated Hb A1c greater than 7,5 % and taking metformin (dose above 1700 mg / day) with or without other secretagogue.

Inclusion Criteria - male or female (not pregnant) , aged between 35 and 65 years who present clinical symptoms of type 2 diabetes between 6 months to 10 years of disease, according to the diagnostic criteria.

Exclusion Criteria - Patients with DM1, DM2 using insulin and other types of diabetes.

T2DM with chronic complications that already have clinical consequences, serum creatinine greater than 1.5 mg/dl, history of heart disease and severe concomitant diseases such as liver, coronary artery, renal, with severe psychiatric or neurological disorders .

Patients with a history of abuse of alcohol and / or illegal drugs or psychotropic medicines in the past six months, hypersensitivity to any of the components of the of study drug formulation.

Eligibility criteria: Inclusion Criteria:

* Diabetes mellitus type 2 between 6 months to 10 years of disease
* Body mass index between 25 and 35 kg/m2
* Fasting glucose between 120 and 250 mg / dL
* Glycated Hb A1c greater than 7,5 % and taking metformin (dose above 1700 mg / day) with or without other secretagogue
* Male or female (not pregnant), who present clinical symptoms of type 2 diabetes between 6 months to 10 years of disease, according to the diagnostic criteria.

Exclusion Criteria:

* Patients with DM1, DM2 using insulin and other types of diabetes
* T2DM with chronic complications that already have clinical consequences
* Creatinine serum greater than 1.4 (female) and 1.5 mg/dl (male)
* History of heart disease and severe concomitant diseases such as liver, coronary artery, renal, with severe psychiatric or neurological disorders
* Patients with a history of abuse of alcohol and/or illegal drugs or psychotropic medicines in the past six months
* Hypersensitivity to any component of the of study drug and placebo formulation.

Primary outcomes:
measure: Fasting Glucose
timeFrame: 4 weeks
measure: HbA1c - glycated haemoglobin
timeFrame: 12 weeks
measure: Cholesterol
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Feira de Santana
country: Brazil
facility: Universidade Estadual de Feira de Santana
state: Bahia
city: Fortaleza
country: Brazil
facility: Centro de Estudos em Diabetes e Hipertensão
state: Ceará
city: Campinas
country: Brazil
facility: Universidade Estadual de Campinas
state: São Paulo
Study officials:
References:
citation: Ramos-Zavala MG, Gonzalez-Ortiz M, Martinez-Abundis E, Robles-Cervantes JA, Gonzalez-Lopez R, Santiago-Hernandez NJ. Effect of diacerein on insulin secretion and metabolic control in drug-naive patients with type 2 diabetes: a randomized clinical trial. Diabetes Care. 2011 Jul;34(7):1591-4. doi: 10.2337/dc11-0357. Epub 2011 May 24.
citation: Velloso LA, Folli F, Perego L, Saad MJ. The multi-faceted cross-talk between the insulin and angiotensin II signaling systems. Diabetes Metab Res Rev. 2006 Mar-Apr;22(2):98-107. doi: 10.1002/dmrr.611.
citation: Tobar N, Oliveira AG, Guadagnini D, Bagarolli RA, Rocha GZ, Araujo TG, Prada PO, Saad MJ. Comment on: Ramos-Zavala et al. Effect of diacerein on insulin secretion and metabolic control in drug-naive patients with type 2 diabetes: a randomized clinical trial. Diabetes Care 2011;34:1591-1594. Diabetes Care. 2012 Feb;35(2):e13; author reply e14. doi: 10.2337/dc11-1856. No abstract available.
citation: Tobar N, Oliveira AG, Guadagnini D, Bagarolli RA, Rocha GZ, Araujo TG, Santos-Silva JC, Zollner RL, Boechat LH, Carvalheira JB, Prada PO, Saad MJ. Diacerhein improves glucose tolerance and insulin sensitivity in mice on a high-fat diet. Endocrinology. 2011 Nov;152(11):4080-93. doi: 10.1210/en.2011-0249. Epub 2011 Sep 6.