Sodium Valproate-loaded Nanospanlastics in Patchy Alopecia Areata in Comparison to Topical Steroids

Study Overview
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Brief Summary
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the aim of this study is to assess the efficacy and safety of sodium valproate-loaded nanospanlastic in the treatment of patchy AA, in comparison to conventional therapy with topical steroids

Detailed Description
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Alpopecia Areata (AA) is the second common cause of non-scarring hair loss, the disease has huge negative impact on patients' quality of life, social and psychological status. The underlying pathogenesis of AA is not fully characterized, Yet the collapse of immune privilege and generation of autoimmune attack against unknown follicular antigens are the most agreed-upon theories behind the disease. In spite of various therapeutic armamentariums available for AA, no single agent has been proven efficacious regarding reversing hair loss and establishing long-term response. keeping in mind the burden of the disease together with lacking effective treatments, a need for further therapies is colossal. Wnt-b catenin pathway is one of the crucial signalling pathways that regulate hair cycling. An increasing body of evidence is supporting the fact that wnt-b catenin pathway is inhibited in AA, and therefore contributing to the hair loss that characteize the disease. Sodium valproate (SV), a well-known anti-epileptic drug, was found to inhibit Glycogen synthase kinase-3beta (GSK3β) in neuronal cells as one of the possible antiepileptic mechanisms of SV. GSK3B is a well-known inhibitor of β-catenin activity in dermal papilla cells (DPCs), and thus induces catagen-like changes in these cells. So the idea of using topical SV to promote hair regrowth via activation of b catenin came up and attracted the interests of investigators. recently an optimized sodium valproate-loaded nanospanlastics topical formula promisingly achieved clinical equivalence with 5% minoxidil lotion in AGA, with a superior safety profile to minoxidil

Official Title
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Assessment of Efficacy and Safety of Sodium Valproate -Loaded Nanospanlastics in Patients With Patchy Alopecia Areata in Comparison to Conventional Therapy With Topical Steroids: a Randomized Controlled Study, With Clinical, Dermoscopic and Molecular Asessements

Conditions
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Alopecia Areata

Intervention / Treatment
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* Drug: the optimized sodium valproate-loaded nanospanlastic dispersion
* Drug: mometasone furoate lotion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with mild to moderate patchy alopecia areata, which is defined as less than 50% involvement of the entire scalp Age above 12 years. Both genders. Patients with patchy alopecia areata, with 2 patches or more Exclusion Criteria: Patients having single patch alopecia areata (at least 2 patches are required, as one patch will be left untreated to exclude the possibility of spontaneous remission) Affection of more than 50% of the scalp area Patients with alopecia totalis or universalis Patients with ophiasis Age: Less than 12 years old. Pregnant or lactating females Patients with history of or existing scalp skin diseases, infections or skin cancer Severe systemic illness (as uncontrolled DM or hypertension, liver or renal diseases) and immune-compromised patients Patients with concomitant autoimmune diseases as suspected by history or confirmed by previous investigations Diagnosis or history of local dermatological disease in the scalp apart from AA such as eczema, seborrheic dermatitis, psoriasis. Any psychiatric illness or psychological state impairing future compliance or influencing expectations of the patient

Ages Eligible for Study
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Minimum Age: 12 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: sodium valproate group<br>Group 1 will be treated with the optimized sodium valproate-loaded nanospanlastic dispersion, twice daily on the affected areas of the scalp for 3 months | Drug: the optimized sodium valproate-loaded nanospanlastic dispersion<br>* participants will apply the optimized sodium valproate-loaded nanospanlastic dispersion twice daily, on the affected areas of the scalp for 3 months<br>|
| Active Comparator: topical steroid group<br>Group 2 will be treated with the marketed mometasone furoate lotion twice daily on the affected areas of the scalp for 3 months | Drug: mometasone furoate lotion<br>* participants will apply marketed mometasone furoate lotion twice daily on the affected areas of the scalp for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Treatment success | defined by achieving ≥ 50% reduction in baseline SALT score at end-of-study and/or achieving patient global assessment of improvement (PGAI) ≥ 50%. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| molecular Assessment of treatment success rate of SV-loaded nanospanlastics in the treatment of mild to moderate patchy AA in comparison to conventional therapy with topical steroids | Assessment of expression of both beta-catenin and Axin2 in lesional scalp of patients with patchy AA before and after treatment with sodium valproate-loaded nanospanlastics, in comparison to conventional therapy with topical steroids | 3 months | 
| Dermoscopic evaluation of hair regrowth | This evaluation will determine the number of dystrophic hairs in the patch area at baseline to be compared after the end of treatment. Markers for dystrophic hairs include exclamation-mark hairs, black dots, yellow dots and pigtail regrowing hair. The percentage of dystrophic hairs will be evaluated on a four-point scale: 3, > 50%; 2, 30-50%; 1, 1-29%; 0, no dystrophic hairs | 3 months | 
| Patient global assessment of improvement | Patient global assessment of improvement will be evaluated at the end of study, and will be scored as the following; (0 =no regrowth; 1 = <25% of regrowth; 2 = 25%-49% of regrowth; 3 = 50%-74% of regrowth; 4 = 75%-99% of re- growth; 5 = 100% of regrowth) | 3 months | 
| Clinical satisfaction of each patient | Clinical satisfaction of each patient will be made using a 10-point visual analogue scale (VAS, 0-10; the 0 level was defined as Not satisfied at all, while a level of 10 was defined as completely satisfied) | 3 months | 
| Subjective assessment of any encountered adverse effects | Subjective assessment of any encountered adverse effects (burning, itching) will also be performed. This will be determined on a four-point scale: 3, strong sensation; 2, moderate sensation; 1, mild sensation; 0, no itching or burning sensation | 3 months | 
| Patient satisfaction regarding characteristics of the used topical treatment | Patient satisfaction regarding characteristics of the used topical treatment, for example (texture, spreadability, hair matting, odour). This will be evaluated on a 3-point scale; 0=unsatisfied, 1=moderately satisfied, 2=extremely satisfied | 3 months | 
| Dermatology Life Quality Index (DLQI) | Dermatology Life Quality Index (DLQI) will be evaluated at baseline and at the end of therapy, using a validated DLQI questionaire | 3 months | 
| Assessment of relapse | Patients who achieved 100% reduction in baseline SALT after 3 months of treatment (end of therapy) were followed up for additional 3 months (end of study) to monitor any relapses. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sodium valproate-loaded nanospanlastic, topical steroids, beta catenin, alopecia areata