A clinical trial to study the effects of two drugs, topical methotrexate vs topical Betamethasone valerate in patients with palmoplantar psoriasis.

Not Applicable

Not yet recruiting

Conditions: Psoriasis vulgaris,

Registration Number: CTRI/2023/08/057113

Lead Sponsor: Jennifer Monica Asirvatham

Brief Summary: 1. INTRODUCTION:

(1.1) Background

Palmoplantar psoriasis is a variant of psoriasis that characteristically affects the skin of the palms and soles. It features hyperkeratotic, pustular, or mixed morphologies. Palmoplantar psoriasis has an average age of onset between 20 and 60 years of age and has a predilection for females 1. Though the incidence has not been determined, the palmoplantar variant of psoriasis comprises 3% to 4% of all cases of psoriasis, which affects 2% to 5% of the population 4-5.It is mostly characterized by well-demarcated, erythematous, scaly plaques of the palms and/or soles. The pathogenesis of palmoplantar psoriasis is similar to psoriasis in that there is an interplay between genetic factors and antigenic triggers. The most commonly associated human leukocyte antigen in psoriasis is HLA-Cw6 4. Psoriasis is related to the psoriasis-susceptibility [PSORS1] locus on chromosome 6p21, though the relation of this gene in palmoplantar psoriasis remains unclear.Thus it has a huge impact on patients quality of life, as it is a chronic recurring condition.5

(1.2) Need of the study:

Many treatments have been used for decades, but palmoplantar psoriasis is resistant to conventional treatments and therefore requires the use of systemic medications, which has a wide range of adverse effects. 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. 1

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.6

As many topical agents have poor permeability,hence the need for use of penetration enhancers (or accelerants) iontophoresis is the use of a direct electric current to increase the penetration of ionic substances into the body for therapeutic purposes has shown good efficacy and allows a higher concentration of the drug to be delivered to a limited area however it leads to ,disruption of epidermis,loss of appendages and fractured collagen in the dermis and could even lead to irreversible skin damage.8-9

Conventionally, steroids have been used for palmoplantar psoriasis for periods up to 6-8 weeks and sometimes even longer while patients treated with vitamin D analogues, tazarotene and tacrolimus combination treatments primarily experienced an irritant contact dermatitis, subjects receiving topical corticosteroids reported a broad spectrum of adverse events, ranging from viral infection, headache, and hypertrichosis to skin atrophy.7

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. 10

(1.3) Study drug and permeation enhancers:

Methotrexate is an oral or parenteral drug used for the treatment of extensive psoriasis. It is a folic acid antagonist. It is an inhibitor of the enzyme dihydro folatereductase. It inhibits DNA synthesis, acting primarily at the S-phase of the cell cycle. The activity of methotrexate in psoriasis is to inhibit epidermal mitosis. However due to its poor permeability its use as a topical agent is limited, thus in our study we are using it with surfactants for enhancing its permeability.2

Surfactants partition into the skin, and interact with the Stratum corneum constituents to induce a temporary increase in skin permeability without causing Nonionic surfactant Transcutol was able to enhance transdermal absorption of MTX and the higher enhancement ratio was obtained with 2% (w/w) concentration of transcutol and addition of salicylic acid increased this ratio 1.Thus the current formulation contains transcutol 2% (w/w) and salicylic acid 6 % (w/w) showed higher enhancement property and can be used clinically for local treatment of psoriasis.Thereby achieving an equivalent permeability as that of iontophoresis without causing irreversible damage of skin.

5. References:

1. Javadzadeh Y, Hamishehkar H. Enhancing percutaneous delivery of methotrexate using different types of surfactants. Colloids and Surfaces B: Biointerfaces. 2011 Feb;82(2):422â€“6.

2. Christophers C, Mrowietz U. Psoriasis. In: Fitzpatrickâ€™s dermatology in internal medicine. Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, Edts., 6th ed. New York: The Mc-Graw-Hill companies Inc.; 2003. p. 407-425.

3. Christopher E.Psoriasis â€“Epidemiology and clinical spectrum. Clin Exp Dermatol 2001; 26:314-320.

4. Faber EM, Mc clintok RP Jr. A current review of psoriasis. Calif Med.1968; 108:440-457.

5. Prasad R, Koul V. Transdermal delivery of methotrexate: past, present and future prospects. Therapeutic Delivery. 2012 Mar;3(3):315â€“25.

6. Chandra A, Aggarwal G, Manchanda S, Narula A. Development of Topical Gel of Methotrexate Incorporated Ethosomes and Salicylic Acid for the Treatment of Psoriasis. Pharmaceutical nanotechnology [Internet]. 2019 [cited 2022 Sep 5];7(5):362â€“74.

7. Bruner CR, Feldman SR, Ventrapragada M, Fleischer AB. A Systematic Review of Adverse Effects Associated with Topical Treatments for Psoriasis. Dermatology Online Journal. 2003;9(1).

8. Prasad R, Koul V, Anand S. Biophysical assessment of DC iontophoresis and current density on transdermal permeation of methotrexate. International Journal of Pharmaceutical Investigation. 2011;1(4):234.

9. Carroll CL, Clarke J, Camacho F, Balkrishnan R, Feldman SR. Topical Tacrolimus Ointment Combined With 6% Salicylic Acid Gel for Plaque Psoriasis Treatment. Archives of Dermatology. 2005 Jan 1;141(1).

10. Tanweer A. Syed, Suhail M. Hadi, 2 Zulfiqar A. Qureshi/ Christine G. Nordstrom. and Shahida M. Ali4 Management of Psoriasis Vulgaris with Methotrexate 0.25% In a Hydrophilic Gel: A Placebo-Controlled, Double-Blind Study.Journal of Cutaneous Medicine and Surgery.2001 July.

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Yet Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

1)Bilateral mild -moderate palmoplantar psoriasis.
2)Patient is 18 years of age or older 3)Both sexes 4)Patients must be able and willing to provide written informed consent and comply with the requirements of this study protocol 5)Patient willing for regular follow up 6)Female patients of childbearing potential must have a negative serum pregnancy test at the Screening visit.

Exclusion Criteria

1)Psoriasis covering >10% of other body surface.
2)Haematological & hepatic disorder patients.
3)Patient is pregnant, breastfeeding, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter.
4)Patient who has used any topical treatment for psoriasis (except non-medicated emollients) in the last 2 weeks before Day 0 with the exception ofÂ shampoos containing tar, salicylic acid or zinc pyrithione.
5)Patient who has used UVB phototherapy or excessive sun exposure less than 14 days before Day 0.
6)Patient who have used any biological therapy for the treatment of psoriasis less than 90 days before day 0.
7)Patient has used any non-biological systemic therapy for the treatment of psoriasis (including PUVA therapy), systemic steroids or systemic immunosuppressants less than 28 days before Day 0.
Investigational non-biologics agents must be discontinued at least 28 days or 5 half-lives prior to Day 0 (whichever is longer).
8)Patient is taking or requires oral or injectable corticosteroids during the study.
Inhaled corticosteroids for stable medical conditions are allowed.
Patients who have used oral or injectable corticosteroids less than 28 days before Day 0 are excluded 9)Patient is currently participating in a clinical trial with an experimental drug or device.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To compare the efficacy of topical Methotrexate gel 1% & topical Betamethasone valerate 0.1% in treatment of palmoplantar psoriasis using salicylic acid as the surfactant for enhancing percutaneous delivery of methotrexate.	Comparison of change in Psoriasis Area & Severity Index (PASI)Â from baseline to 8 week.

Secondary Outcome Measures

Name	Time	Method
Comparison of adverse events occurring withÂ Betamethasone valerate & methotrexate.	Comparison of change in erythema, fissuring & scaling between the study groups at the end of 2nd,4th,6th & 8th week.

Trial Locations

Locations (1): Sri Ramachandra Medical College
🇮🇳
Chennai, TAMIL NADU, India
Sri Ramachandra Medical College
🇮🇳Chennai, TAMIL NADU, India
Dr Jennifer Monica
Principal investigator
9663740096
jennifermonica945@gmail.com