A Novel Formulation of Sildenafil-loaded Nanocarriers for Treatment of Alopecia Areata
NCT Number: NCT06527729
Status: COMPLETED
Study Type: INTERVENTIONAL
Phases: EARLY_PHASE1
Conditions: Alopecia Areata
Interventions: DRUG: sildenafil-loaded liposomes|DRUG: minoxidil gel
Sponsor: Assiut University
Sex: ALL
Age: CHILD, ADULT
Enrollment: 28
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (PARTICIPANT)|Primary Purpose: TREATMENT
Start Date: 2021-07-01
Completion Date: 2022-10-01
Locations: Faculty of Medicine, Assiut university, Assiut, Egypt

Summary:
Alopecia areata (AA) is a common cause of nonscarring alopecia that occurs in a patchy, confluent, or diffuse pattern. Many theories were implicated in pathogenesis of AA, such as an autoimmune lymphocytic attack of the hair, genetic basis, and environmental factors. Clinically, AA presents as a well-circumscribed patch of sudden hair loss. It affects any hair bearing area with the scalp being the most commonly affected site .

Dermoscopy is a noninvasive technique for the clinical diagnosis of many skin diseases. Dermoscopy is now considered as a valuable tool in diagnosis of variable skin lesions. Scalp dermoscopy (Trichoscopy) does not only facilitate diagnosis of hair disorders but also give clues about disease stage and progression.

The most common trichoscopic features of AA are yellow dots, micro-exclamation mark hairs, tapered hairs, black dots, broken hairs, and regrowing upright or regrowing coiled hairs. Trichoscopic characteristics have a clinical significance in AA for diagnosis and prognosis.

The treatment of alopecia areata involves promotion of hair growth (for instance with topical minoxidil application), immunosuppression (intralesional or systemic steroid therapy, phototherapy) or immunomodulation (anthralin, dinitrochlorobenzene, diphenylcyclopropenone, squaric acid dibutylester).Unfortunately, there is currently no cure for this chronic disease, and despite the presence of a wide variety of therapeutic options, none is universally proven to induce and/or sustain remission. Development of new drugs and formulations is urgently needed

Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, is known to increase the intracellular level of cyclic guanosine monophosphate (cGMP), which causes vasodilation. Sildenafil was first approved in 1998 for erectile dysfunction, but since then additional uses for the drug have been found. A previous study demonstrated the significant therapeutic potential of sildenafil on hair growth and proposed its potential use in treatment of alopecia. It has been shown that it enhances proliferation of human dermal papilla cells (hDPCs) and up-regulates the mRNA expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which are responsible for hair growth. Additionally, sildenafil up-regulates the levels of phosphorylated ERK and accelerates anagen induction by stimulating perifollicular vessel formation after topical application in mice.

Primary Outcome Measures: The efficacy of topical sildenafil-loaded liposomes formulation compared with topical minoxidil therapy for the treatment of patchy alopecia areata, the comparison of serial photographs of the lesions to the baseline ones. Severity of Alopecia Tool (SALT) score was calculated, at baseline, 4 weeks and 8 weeks and the average percentage of hair re-growth was determined using the SALT scoring system for hair re-growth and graded as A0: no change or further hair loss, A1: 1-24% hair re-growth, A2: 25-49% hair re-growth, A3: 50-74% hair regrowth, A4: 75-99% hair re-growth, and A5: 100% hair re-growth, 8 weeks|Dermoscopic asessment, Dermoscopic examination was carried out before treatment and at 4 and 8 weeks, using the handheld dermoscope (DermLite DL4, 3Gen, Inc., San Juan Capistrano, CA 92675). Baseline and post-therapy digital photographs of dermoscopic fields were taken using an iPhone 6S smartphone camera. Dermoscopic features of AA were evaluated including yellow dots, black dots, broken hair, exclamation-mark hairs, short vellus hair and regrowing hair. Two dermoscopic fields were examined; one from the center and the other at 3 o'clock position of the alopecia patch. Trichoscopic parameters in each field were evaluated and quantified., 8 weeks