Study of Efficacy of Metformin in the Treatment of Acanthosis Nigricans in Children With Obesity

Study Overview
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Brief Summary
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Obesity is often accompanied by insulin resistance and/or hyperinsulinemia. Acanthosis nigricans (AN) is a skin condition commonly present on the neck of obese children. Metformin is a useful drug for conditions characterized by insulin resistance.The aim of this study is to compare the efficacy of metformin versus placebo on AN lesions of the neck as well as their effects on metabolic and anthropometric variables in a sample of obese children. This is a 12-week randomized, double-blind randomized trial involving obese children with AN to receive either metformin or placebo. Evaluations will be performed every three weeks. Clinical, histological and colorimetric assessments of AN lesions will be compared initially and at the conclusion of the study.

Detailed Description
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Acanthosis nigricans (AN) are lesions affecting localized areas of the skin in persons with obesity and/or hyperinsulinemia. Roughening of the skin is related with histological papillomatosis and the skin darkening is due to hyperkeratosis. Biochemical mechanisms for developing this hyperplastic lesion involve local cutaneous growth factors. Nearly 40% of Native American teenagers have acanthosis nigricans, whereas about 13% of African American, 6% of Hispanic, and less than 1% of white, non-Hispanic children aged 10-19 have clinically apparent acanthosis nigricans. AN is a clinical surrogate of laboratory-documented hyperinsulinemia. The aim of this study is to compare the efficacy of metformin versus placebo on AN lesions of the neck as well as their effects on metabolic (HOMA, triglycerides, cholesterol) and anthropometric variables (BMI, waist) in a sample of obese children. This is a 12-week randomized, double-blind randomized trial involving obese children with AN to receive either metformin or placebo. Evaluations will be performed every three weeks. Clinical, histological and colorimetric assessments of AN lesions will be compared initially and at the conclusion of the study. Burke´s scale, papillomatosis and hyperkeratosis, and the L* axis of will be used to measure the AN improvement.

Official Title
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Double-blind Randomized Trial Using Oral Metformin Versus Placebo in the Treatment of Acanthosis Nigricans in Children With Obesity

Conditions
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Acanthosis Nigricans

Intervention / Treatment
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* Drug: Metformin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent from children and parents. Children younger than 18 years. Clinical diagnosis of acanthosis nigricans. Obesity. Exclusion Criteria: Diabetes mellitus. Neurological diseases. Congenital diseases. Oral treatment for obesity in the last two months. Topical treatment for the last two months.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>500 mg metformin oral intake before main meal | Drug: Metformin<br>* One tablet of 500 mg will be ingested before the main meal<br>* Other names: Riomet;|
| Placebo Comparator: Placebo<br>Placebo tablet before main meal. | Other: Placebo<br>* A placebo tablet will be ingested daily before main meal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement of acanthosis nigricans | Initial and after intervention assessment of acanthosis nigricans using the quantitative scale of Burke (Diabetes Care 22:1655-1659, 1999). Five anatomical sites were chosen to assess the presence and extent of AN: neck, axilla, knuckles, elbows, and knees. The neck and axilla are graded for severity on a scale from 0 to 4. For AN present on the neck, texture of the affected area is also measured on a scale from 0 to 3. Knuckles, elbows, and knees are graded as AN present (1) or absent (0). Score goes from 0 to 14. | baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological improvement of acanthosis nigricans | Epidermal and stratum corneum thickness of 3 mm skin samples obtained from neck will be measured using an image processing software initially and at the end of trial. | baseline and 12 weeks | 
| Depigmentation of acanthosis nigricans | Quantification of pigmentation change of lesions by means of the L axis of the CIE system. 0 is pure white, 100 y total dark. Initially, and at the end of study. | baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acanthosis nigricans, obesity, children, metformin