Adipokines in Obese Adolescents With Insulin Resistance

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare serum concentrations of inflammatory cytokines, interleukin 6 (IL-6), High-sensitivity C-reactive protein (hs-CRP), adiponectin, and tumour necrosis factor alpha (TNFα), before and after three months treatment with metformin in obese adolescents with insulin resistance (IR).

Detailed Description
-----------------
The increased prevalence of obesity in pediatric patients is a public health problem particularly because of the difficulties involved with changing lifestyles. Current studies of obese children and adolescents show increased insulin resistance (IR) and chronic inflammatory states. These conditions increase the risk of disability and/or premature death. The current treatment schemes for obese children are conservative and are focused on changing their lifestyles (exercise and dietary plans). However, metabolic conditions, such as IR, dyslipidemia, and inflammatory processes, are perpetuated. Metformin is a biguanide that is used for adolescents with diabetes mellitus and polycystic ovarian syndrome. Several clinical trials with metformin for obese pediatric patients have observed decreases in IR, decreases in weight, and improvements in lipid metabolism. Adipose tissue is not only an energy repository, but also plays an immunological role by the secretion of cytokines. Both overweight adults and adolescents show decreases in adiponectin levels and increases in tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6). IL-6 can stimulate the production of high-sensitivity C-reactive protein (hs-CRP), which is considered to be a risk marker for the development of cardiovascular disease.

Official Title
-----------------
Inflammatory Mediators in Obese Adolescents With Insulin Resistance Following Metformin Treatment: Controlled Randomized Clinical Trial

Conditions
-----------------
Obesity

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obesity defined as Body Mass Index (BMI) ≥ percentile 95 Tanner stage ≥ 2 Insulin resistance defined as Basal insulin > 15 µU/mL or Homeostasis Model Assessment index (HOMA) > 4.5 Patients' parents signed written consents when they and their adolescent children agreed to enroll Exclusion Criteria: Glucose intolerance Diabetes mellitus (type 1 or 2) Anemia (Hb < 10 g/dL) Plasma creatinine > 1.4 mg/dL Abnormal hepatic function Any associated Disease (Pulmonary, Infection, Autoimmune Disease) History of lactic acidosis

Ages Eligible for Study
-----------------
Minimum Age: 9 Years
Maximum Age: 18 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 |
| --- | --- |
| Experimental: Metformin<br>Tablet of 500 mg metformin, oral every 12 hours (total metformin dose of 1 g/day) for 3 months. | Drug: Metformin<br>* Tablet of 500 mg metformin, oral every 12 hours (total metformin dose of 1 g/day) for 3 months.<br>* Other names: Dabex;|
| Placebo Comparator: Placebo<br>Tablet of 500 mg oral placebo every 12 hours for 3 months. | Drug: Placebo<br>* Tablet of 500 mg oral placebo every 12 hours for 3 months.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adiponectin | Change from baseline in Adiponectin after 3 months of treatment. | baseline and 3 months | 
| High-sensitivity C-reactive Protein | Change from baseline in High-sensitivity C-reactive protein after 3 months of treatment. | baseline and 3 months | 
| Interleukin 6 | Change from baseline in Interleukin 6 after 3 months of treatment. | baseline and 3 months | 
| Tumour Necrosis Factor Alpha | Change from baseline in Tumour necrosis factor alpha after 3 months of treatment. | baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Plasma Glucose | Change from baseline in Fasting plasma glucose after 3 months of treatment. | baseline and 3 months | 
| Fasting Insulin | Change from baseline in Fasting insulin after 3 months of treatment. | baseline and 3 months | 
| Body Mass Index | Change from baseline in Body Mass Index after 3 months of treatment. | baseline and 3 months | 
| Waist Circumference | Change from baseline in Waist circumference after 3 months of treatment. | baseline and 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metformin, Obesity, Insulin resistance, Interleukin six, Adiponectin, High sensitivity C reactive protein., Tumour Necrosis Factor alpha