Topical Metformin Emulgel VS Salicylic Acid Peeling in Treatment of Acne Vulgaris

Study Overview
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Brief Summary
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Acne Vulgaris (AV ) is a common skin disorder worldwide, affecting all ages and races, considered as a long term chronic inflammatory disease of the skin.It affects nearly 85% of adolescents and about 30% of adults which is known as post- adolescent acne that often occurs in individuals aged 25 years or older particularly women. Acne lesions, which may be papules, pustules, or nodules commonly affecting face, chest and back therefore acne patients may suffer from emotional distress due to its chronicity and potential outcomes which include physical scars and persistent hyperpigmentation. The pathophysiology of AV involves four factors: abnormal follicular keratinization, hyperseborrhea, Cutibacterium acnes proliferation in the pilosebaceous unit and inflammatory mediators released into the skin. Diet is considered to be one of the main factors influencing the induction and aggravation of acne, though this is still debatable. Previous researches have focused on glycemic load, and hyperinsulinemia which lead to an increase in the concentration of insulin-like growth factor (IGF-1), which has been reported to affect androgen metabolism and lipogenesis Additionally, IGF-1 has been shown to upregulate inflammatory cytokines. A correlation between the severity of acne and the level of serum IGF-1 has also been reported. Previous clinical studies showed that a low glycemic diet can decrease both the size of the sebaceous gland and the number of inflammatory lesions

Detailed Description
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Several treatment modalities have been used to treat AV. Topical therapies include antibiotics, azelaic acid, benzoyl peroxide, and retinoids. Systemic treatments include antibiotics, hormonal therapy, and isotretinoin in addition to physical modalities as chemical peeling . Chemical peeling is a safe, efficacious, and cost-effective procedure for treating various skin disorders and for enhancing cosmetic appearance. The principle of peeling involves controlled chemical injury to the skin in order to promote it to rejuvenate, leading to smoothening of the skin and improvement of its surface texture . As patients become more concerned about the risks and side-effects of acne medications such as antibiotics and isotretinoin, other options are needed . Metformin is an oral antihyperglycemic agent often used to treat overweight type 2 diabetic patients. It decreases hepatic glucose output and increases glucose utilization by muscles and adipocytes by increasing insulin sensitivity . Notably, metformin has been shown to suppress the mammalian target of rapamycin complex (mTORC1) activity . mTORC, also known as the mechanistic target of rapamycin, is a central cell growth regulating kinase that forms large molecular complexes in all eukaryotic cells. Rapamycin is an mTORC1-specific inhibitor, which complexes with the FK506-binding 12 kDa protein (FKBP12). Rapamycin analogs have been used clinically to treat a number of human diseases, including cancer. A wide range of both extra- and intracellular signals, including growth factors, nutrient status and stress conditions, have been shown to regulate mTORC1 to control cell growth . Hence, it is plausible that metformin through inhibition of mTORC1 improves acne as AV is one of the mechanistic target of rapamycin complex 1 (mTORC1)-driven diseases. Moreover, metformin has been suggested for the treatment of other insulin resistant-related skin disorders such as hirsutism, hidradenitis suppurativa, and acanthosis nigricans . In order to get a benefit from the anti-inflammatory effect of metformin on the skin, the best option is to enhance its dermal effects, therefore, its side effects will be less through the topical administration route . Actually, by applying a topical form of this drug on acne spots, mTORC1 over activation in skin cells can be inhibited which leads to disappearance of acne spots . Salicylic acid (SA) is a safe and efficacious peeling agent for a number of dermatological and cosmetic problems, including acne vulgaris . SA peels soften the stratum corneum and cause skin shedding by loosening the intracellular matrix and corneocyte connections which can lead to an improvement in non-inflammatory comedones . Also, SA inhibits the arachidonic acid cascade leading to a decrease in inflammatory lesions . In our study, we chose the emulgel formulation as a topical metformin form to increase the efficacy and absorption in treatment of AV. Emulgel used will be optimized for biocompatibility, consistency and chemical compatibility with metformin.

Official Title
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Efficacy and Safety of Topical Metformin Emulgel Versus Salicylic Acid Peeling in Treatment of Acne Vulgaris: A Split Face Study

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: Topical Metformin Emulgel and salicylic acid
* Diagnostic Test: Insulin- Like growth factor (ILGF-1)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both males and females will be included. Patients older than 18 years of age. Patients with mild and moderate AV. Patients with Fitzpatrick skin type III, IV and V. Exclusion Criteria: Severe acne. Patients under treatment with contraceptive pills or received any kinds of systemic or topical acne medication in the last 2 months (isotretinoin, antibiotics, topical products) or corticosteroid, lithium, growth hormone, systemic metformin, vitamin B12, whey proteins, and estrogenic-progestogens. History of hypertrophic/keloid scar formation. Pregnancy and lactation. Recurrent herpes infection. Subjects with diseases that affect IGF-1 levels such as diabetes, metabolic syndrome, and acromegaly. Conditions that affect liver or thyroid function, celiac disease and inflammatory bowel diseases.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: Patients will use salicylic acid 30% peeling on the right side of the face and topical metformin emulgel on the left side
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical Metformin Emulgel and salicylic acid<br> | Drug: Topical Metformin Emulgel and salicylic acid<br>* Combination Product: Topical metformin emulgel topical metformin emulgel will be used on the left side of the face twice daily (home use). Procedure/Surgery: Salicylic acid Patients will have salicylic acid 30% peeling on the right side of the face as a peeling session every two weeks. Sessions will be done by well trained physician. Other Names: • 2-hydroxybenzoic acid<br>Diagnostic Test: Insulin- Like growth factor (ILGF-1)<br>* 3 ml blood for serum sample for estimation of Insulin- Like growth factor (ILGF-1) by ELISA kit will be taken from every patient before and after use of topical metformin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of the medications | by counting the number of inflammatory, non-inflammatory and total lesions at baseline and every 4 weeks during the treatment. | 12 weeks | 
| Evaluate effect of topical metformin on decreasing serum concentration of insulin-like growth factor 1 (IGF-1) | Evaluate effect of topical metformin on decreasing serum concentration of insulin-like growth factor 1 (IGF-1) by serum sample that will be taken from every patient before and after use of topical metformin. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of tolerability | by interviewing the patients about any sign/symptom of adverse reactions (erythema, peeling, burning sensation, dryness and pruritus). | 12 weeks | 
| Assessment of patient satisfaction | by quartile grading system | 12 weeks |