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

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

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

Study Overview

• Status: Completed
• Conditions: Alopecia Areata
• Intervention / Treatment: Drug: the optimized sodium valproate-loaded nanospanlastic dispersion; Drug: mometasone furoate lotion

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Kasralainy Hospital, Dermatology Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sodium valproate group; 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; participants will apply the optimized sodium valproate-loaded nanospanlastic dispersion twice daily, on the affected areas of the scalp for 3 months
Active Comparator: topical steroid group; 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; participants will apply marketed mometasone furoate lotion twice daily on the affected areas of the scalp for 3 months

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital
• Investigators: Principal Investigator: heba ahmed, Msc in dermatolo, Kasralainy hospital, faculty of medicine, Cairo university

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Actual): January 1, 2023
• Study Completion (Actual): April 1, 2023

Study Registration Dates

• First Submitted: August 14, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: topical steroids; alopecia areata; sodium valproate-loaded nanospanlastic; beta catenin
• Additional Relevant MeSH Terms: Skin Diseases; Pathological Conditions, Anatomical; Hypotrichosis; Hair Diseases; Alopecia; Alopecia Areata; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anti-Inflammatory Agents; Dermatologic Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Anticonvulsants; Antimanic Agents; Anti-Allergic Agents; Valproic Acid; Mometasone Furoate
• Other Study ID Numbers: 264199200

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No