Adipokines in Obese Adolescents With Insulin Resistance

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01410604

Enrollment

Registered

2011-08-05

Start date

2007-01-31

Completion date

2010-03-31

Last updated

2012-04-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity

Keywords

Metformin, Obesity, Insulin resistance, Interleukin six, Adiponectin, High sensitivity C reactive protein., Tumour Necrosis Factor alpha

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.

Interventions

DRUGMetformin

Tablet of 500 mg metformin, oral every 12 hours (total metformin dose of 1 g/day) for 3 months.

DRUGPlacebo

Tablet of 500 mg oral placebo every 12 hours for 3 months.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

9 Years to 18 Years

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

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

Countries

Mexico

Participant flow

Recruitment details

Subjects were enrolled between January 2007 and December 2009 in the Pediatric Obesity Clinics (POC) from third level Mexican Hospitals: the HMFG, located in the Federal District (country's capital), and the HRAEB, located in the city of Leon in the state of Guanajauto.

Participants by arm

Arm	Count
Metformin	15
Placebo	16
Total	31

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	2	1
Overall Study	Lost to Follow-up	1	0
Overall Study	Physician Decision	0	1

Baseline characteristics

Characteristic	Placebo	Metformin	Total
Age, Categorical <=18 years	16 Participants	15 Participants	31 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age Continuous	14.12 years STANDARD_DEVIATION 1.2	12.56 years STANDARD_DEVIATION 2.25	13.37 years STANDARD_DEVIATION 1.92
Region of Enrollment Mexico	16 participants	15 participants	31 participants
Sex: Female, Male Female	10 Participants	12 Participants	22 Participants
Sex: Female, Male Male	6 Participants	3 Participants	9 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 15	0 / 16
serious Total, serious adverse events	2 / 15	1 / 16