Topical Methotrexate Microemulsion in the Treatment of Plaque Psoriasis

Study Overview
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Brief Summary
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Psoriasis is a chronic relapsing dermatological disease which often necessitates a long-term therapy and occurs in a significant percent of the population . It affects the skin and sometimes the nails and joints of patients . Psoriatic patients are frequently categorized into two groups: mild or moderate to severe psoriasis, depending on the clinical severity of the lesions, the percentage of affected body surface area, and patient quality of life . Topical drug therapy is the cornerstone in the treatment of mild to moderate psoriasis. It offers a direct targeting of affected skin by avoiding systemic adverse events . Several topical therapies are available for the treatment of psoriasis such as topical steroid , topical vitamin D3 analogues (calcipotriol),tar, anthraline, topical tacrolimus (a non-steroidal calcineurin inhibitor) and tazarotene (a third-generation retinoid) . However, they do not provide an adequate response owing to the inadequate percutaneous absorption and poor patient compliance caused by greasiness and stickiness of some formulations, and some patients even remain untreated . So that, patient satisfaction with available topical treatments remains modest .

Detailed Description
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Methotrexate was US Food and Drug Administration approved for the treatment of psoriasis, and is currently recommended for practically all forms of moderate or severe psoriasis, including psoriatic arthritis . Methotrexate competitively inhibits dihydrofolate reductase enzyme which converts dihydrofolate to tetrahydrofolate (fully reduced folic acid); the latter being a necessary cofactor in the synthesis of DNA . Because systemic Methotrexate is associated with several adverse effects, topical Methotrexate has become a more-interesting alternative . However, the topical action of Methotrexate is challenging, since it suffers limited percutaneous diffusivity owing to its aqueous solubility, its ionization at physiological pH, and unfavorable lipid/water coefficient . A remedy to this problem might be the utilization of a suitable customized nano-based delivery system for enhancing the topical percutaneous penetration of MTX for treatment of psoriasis . Micro emulsions are among the most promising nanocarriers, being composed of aqueous and oily phases in addition to surfactants and cosurfactants . Only one study used micro emulsion as a topical nanocarrier for MTX, and jojoba oil will be selected as the oily phase of the micro emulsion since it exhibits moisturizing and anti-inflammatory effects which are beneficial in psoriasis treatment . The physical therapies used for the treatment of psoriasis include PUVA, broad band ultraviolet ray, Narrowband ultraviolet B and monochromatic excimer laser and light. Narrowband ultraviolet B (307-311 nm) showed efficacy in the treatment of psoriasis. This therapeutic approach considers that psoriasis patients undergoing phototherapy usually receive high cumulative doses of radiation during their lives, thus leading to secondary cutaneous disorders, like photoaging, telangiectasias, excessive tanning . On the contrary, The monochromatic excimer light device delivers ultraviolet B wavelength at 308 nm only to the lesional skin, could lower all these collateral effects dramatically and decreasing the total dose of radiation. Moreover, the treatment may be tailored to each affected area with different doses of ultraviolet makes monochromatic excimer laser and light mostly appreciated to a large part of patients, thus increasing treatment compliance, which is particularly useful when we have to deal with long-lasting therapeutic protocols. Finally, the possibility to focus the radiations on skin lesions is believed to reduces the risks of acute and chronic side effects in the uninvolved safe skin Several studies showed its effectiveness in the treatment of psoriasis as a monotherapy or in combination with several topical therapies such as flumetasone, dithranol, calcipotriol , but no study investigate its efficacy in combination with topical methotrexate yet. In recent years, the new biological therapies (monoclonal antibodies, receptor fusion proteins and similar) have been developed to manage psoriasis in its inner mechanisms of immune regulation. However, the legal (i.e. FDA and EMA-approved use of biologics in psoriasis) and scientific limitations (i.e. guidelines) for the use of biologics, together with the major possible medical involvements connected to this category of therapeutic agents and their expensive cost, make of them a treatment dedicated to a few well-chosen patients .

Official Title
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The Efficacy and Safety of Topical Methotrexate Microemulsion in Combination With Excimer Light and Narrow Band-ultraviolet B in the Treatment of Plaque Psoriasis

Conditions
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Psoriasis, Methotrexate

Intervention / Treatment
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* Drug: topical methotrexate micoemulsion
* Device: Excimer light
* Device: Narrow band ultraviolet B


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Thirty patients with mild psoriasis will be recruited from the Dermatology Outpatient Clinic, Assiut University Hospital. The diagnosis will be based upon the clinical characteristics of plaque psoriasis. Patients will be included after they have stopped any systemic therapy for at least 8 weeks and topical therapy for at least 2 weeks. Exclusion Criteria: Patients having cardiovascular, renal or liver diseases. Patients with photosensitive or psychological disorders or immunodeficient patients. Pregnant or lactating woman

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: topical methotrexate microemulsion<br>Group(A): topical methotrexate micro emulsion formulation, each patient will be instructed to apply a very thin film of 0.5 ml of it over the three psoriatic plaques three times weekly . | Drug: topical methotrexate micoemulsion<br>* The selected microemulsion composition consists of 40% Jojoba oil, 45% Tween-80 and Span-85 at a ratio of 3:1 as surfactant and co surfactant, respectively and 15% water. The chosen concentration was based on preliminary studies conducted which delineated that these ratios provided the best skin deposition based on factorial skin modelling.The prepared microemulsions contains 0.1% methotrexate<br>* Other names: Methotrexate nano-emulsion;|
| Experimental: combination of topical methotrexate microemulsion and excimer light<br>Group(B) : excimer laser will be done twice weekly on a different psoriatic plaques in combination with topical methotrexate micro emulsion for a total treatment course of 12 weeks. | Drug: topical methotrexate micoemulsion<br>* The selected microemulsion composition consists of 40% Jojoba oil, 45% Tween-80 and Span-85 at a ratio of 3:1 as surfactant and co surfactant, respectively and 15% water. The chosen concentration was based on preliminary studies conducted which delineated that these ratios provided the best skin deposition based on factorial skin modelling.The prepared microemulsions contains 0.1% methotrexate<br>* Other names: Methotrexate nano-emulsion;Device: Excimer light<br>* the excimer laser will be done twice weekly for a total treatment course of 12 weeks.<br>|
| Experimental: combination of topical methotrexate microemulsion and narrow band-ultraviolet B<br>Group(C) : Narrow band ultraviolet B will be done twice weekly on a different psoriatic plaques in combination with topical methotrexate micro emulsion for a total treatment course of 12 weeks | Drug: topical methotrexate micoemulsion<br>* The selected microemulsion composition consists of 40% Jojoba oil, 45% Tween-80 and Span-85 at a ratio of 3:1 as surfactant and co surfactant, respectively and 15% water. The chosen concentration was based on preliminary studies conducted which delineated that these ratios provided the best skin deposition based on factorial skin modelling.The prepared microemulsions contains 0.1% methotrexate<br>* Other names: Methotrexate nano-emulsion;Device: Narrow band ultraviolet B<br>* the Narrow band ultraviolet B will be done twice weekly for a total treatment course of 12 weeks.<br>* Other names: NB-UVB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of clinically improved patients using psoriasis severity index | clinical assessment using psoriasis severity index | three months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis