Botox Versus Tacrolimus in Psoriasis Vulgaris

Psoriasis Vulgaris Clinical Trial

Official title:

Efficacy and Safety of Mesobotox as a Potential New Therapeutic Modality of Psoriasis Vulgaris in Comparison/Combination With Topical Calcineurin Inhibitor

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06203470
• Other study ID #: BTP
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 2024
• Est. completion date: October 2026

Study information

• Verified date: June 2024
• Source: Assiut University
• Contact: Amira Ali, MD
• Phone: 0201005263721
• Email: amiraali21[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Psoriasis is a systemic chronic relapsing immune-mediated disease which often requires a long-term therapy. Psoriasis occurs in around 2-3% of the total global population. In Egypt, the prevalence of psoriasis ranges between 0.19% and 3%.

Besides, it could have profound implications on the patients' psychological state and quality of life.

It is presented by erythematous, scaly plaques over the preferred sites. The pathogenesis of this highly complex disease is still far from being fully understood. Keratinocytes' hyperproliferation and immune system dysfunctions are well recognized contributors, with numerous treatments targeting these unique immunologic dysfunctions.

Description:

Neurogenic inflammation has been suggested as an etiopathogenic factor of psoriasis. Previous reports revealed an increased concentration of nerve fibers as well as a high level of neuropeptides of cutaneous sensory nerve origin, primarily Substance P and calcitonin gene-related peptide (CGRP).

Some investigators reported improvement of psoriatic plaques after injuries that compromised peripheral nerves. Hence, it was postulated that cutaneous sensory afferent neurons are involved in the etiopathogenesis of psoriasis and may serve as a potential therapeutic target.

Substance P (SP) is a neuropeptide of sensory nerve origin that can influence the immune cell functions and the inflammatory responses in psoriasis. By binding to NK1R on T cells, SP can stimulate Th17 cell differentiation and production of interleukin-17A cytokine (IL-17A). IL-17A is a key effector cytokine in psoriasis, by releasing several pro-inflammatory cytokines, such as TNF alpha, stimulating abnormal keratinocytes' proliferation and promoting angiogenesis.

Topical drug therapy is the cornerstone of the treatment of mild to moderate psoriasis. It offers a direct skin targeting and avoids systemic adverse events. Several topical therapies are currently available for the treatment of psoriasis such as topical steroids, topical vitamin D3 analogues e.g. Calcipotriol, tar, anthraline, topical calcineurin inhibitors and tazarotene.

Tacrolimus, formerly known as FK506, is a macrolide antibiotic possessing immunosuppressive properties. Tacrolimus disrupts the intracellular activation of T-lymphocytes and inhibits the ability of calcineurin to regulate gene transcription. Thus, tacrolimus intervenes at an early stage of T-cell activation, leads to several secondary consequences providing effective and therapeutically efficient results to overcome problems associated with psoriatic skin disease.

Botulinum Toxin-A (BoNT-A) is an injectable neuromodulator produced by Clostridium Botulinum, a Gram-positive bacillus that causes Botulism. The clinical utility of BoNT-A originates from the ability to block muscular contractions by inhibiting neurotransmission between peripheral nerve cells and muscle fibers. Currently, BoNT-A is widely used for multiple aesthetic concerns that can be alleviated by local muscle relaxation, such as upper facial dynamic rhytides .

Botulinum Toxin-A can inhibit the release of neurotransmitters e.g. SP from the sensory motor neurons. SP is an important neuropeptide in the pathophysiological process of cutaneous neurogenic inflammation. Thus, it was hypothesized that BoNT-A can potentially be used for treating several inflammatory skin diseases, including psoriasis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: October 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients with clinical diagnosis of mild to moderate psoriasis vulgaris

• Patients who stopped any systemic therapy or phototherapy for at least 3 months and topical therapy for at least 4 weeks prior to enrollment.

Exclusion Criteria:

• • Psoriasis vulgaris involving > 10% of the body surface area, pustular or erythrodermic psoriasis.

• Patients with neuromuscular disease or history of epilepsy.

• Pregnant or lactating females.

• Patients with any current dermatological disease.

• Patients with any current systemic disease.

Related Conditions & MeSH terms

• Psoriasis
• Psoriasis Vulgaris

Intervention

Drug:
• Botulinum Toxin-A
Botulinum Toxin-A (BoNT-A) is an injectable neuromodulator produced by Clostridium Botulinum, a Gram-positive bacillus that causes Botulism.
• Tacrolimus
topical Calcineurin inhibitor

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (17)

Amalia SN, Uchiyama A, Baral H, Inoue Y, Yamazaki S, Fujiwara C, Sekiguchi A, Yokoyama Y, Ogino S, Torii R, Hosoi M, Ishikawa O, Motegi SI. Suppression of neuropeptide by botulinum toxin improves imiquimod-induced psoriasis-like dermatitis via the regulation of neuroimmune system. J Dermatol Sci. 2021 Jan;101(1):58-68. doi: 10.1016/j.jdermsci.2020.11.003. Epub 2020 Nov 6. — View Citation

Armstrong AW, Mehta MD, Schupp CW, Gondo GC, Bell SJ, Griffiths CEM. Psoriasis Prevalence in Adults in the United States. JAMA Dermatol. 2021 Aug 1;157(8):940-946. doi: 10.1001/jamadermatol.2021.2007. — View Citation

Barros PO, Ferreira TB, Vieira MM, Almeida CR, Araujo-Lima CF, Silva-Filho RG, Hygino J, Andrade RM, Andrade AF, Bento CA. Substance P enhances Th17 phenotype in individuals with generalized anxiety disorder: an event resistant to glucocorticoid inhibition. J Clin Immunol. 2011 Feb;31(1):51-9. doi: 10.1007/s10875-010-9466-6. Epub 2010 Sep 24. — View Citation

Bera MM, Lu B, Martin TR, Cui S, Rhein LM, Gerard C, Gerard NP. Th17 cytokines are critical for respiratory syncytial virus-associated airway hyperreponsiveness through regulation by complement C3a and tachykinins. J Immunol. 2011 Oct 15;187(8):4245-55. doi: 10.4049/jimmunol.1101789. Epub 2011 Sep 14. — View Citation

Chen SQ, Chen XY, Cui YZ, Yan BX, Zhou Y, Wang ZY, Xu F, Huang YZ, Zheng YX, Man XY. Cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes. Cell Mol Life Sci. 2022 Apr 30;79(5):267. doi: 10.1007/s00018-022-04299-x. — View Citation

Goff KL, Karimkhani C, Boyers LN, Weinstock MA, Lott JP, Hay RJ, Coffeng LE, Norton SA, Naldi L, Dunnick C, Armstrong AW, Dellavalle RP. The global burden of psoriatic skin disease. Br J Dermatol. 2015 Jun;172(6):1665-1668. doi: 10.1111/bjd.13715. Epub 2015 May 6. No abstract available. — View Citation

Gonzalez C, Franco M, Londono A, Valenzuela F. Breaking paradigms in the treatment of psoriasis: Use of botulinum toxin for the treatment of plaque psoriasis. Dermatol Ther. 2020 Nov;33(6):e14319. doi: 10.1111/dth.14319. Epub 2020 Oct 8. — View Citation

Kattimani V, Tiwari RVC, Gufran K, Wasan B, Shilpa PH, Khader AA. Botulinum Toxin Application in Facial Esthetics and Recent Treatment Indications (2013-2018). J Int Soc Prev Community Dent. 2019 Mar-Apr;9(2):99-105. doi: 10.4103/jispcd.JISPCD_430_18. Epub 2019 Apr 12. — View Citation

Khattab FM, Samir MA. Botulinum toxin type-A versus 5-fluorouracil in the treatment of plaque psoriasis: Comparative study. J Cosmet Dermatol. 2021 Oct;20(10):3128-3132. doi: 10.1111/jocd.14306. Epub 2021 Jul 14. — View Citation

Khattab FM. Evaluation of Botulinum Toxin A as an Optional Treatment for Atopic Dermatitis. J Clin Aesthet Dermatol. 2020 Jul;13(7):32-35. Epub 2020 Jul 1. — View Citation

Kubanov AA, Katunina OR, Chikin VV. Expression of Neuropeptides, Neurotrophins, and Neurotransmitters in the Skin of Patients with Atopic Dermatitis and Psoriasis. Bull Exp Biol Med. 2015 Jul;159(3):318-22. doi: 10.1007/s10517-015-2951-4. Epub 2015 Jul 24. — View Citation

Omar SS, Helaly HA. Prevalence of ocular findings in a sample of Egyptian patients with psoriasis. Indian J Dermatol Venereol Leprol. 2018 Jan-Feb;84(1):34-38. doi: 10.4103/ijdvl.IJDVL_1239_15. — View Citation

Popescu MN, Beiu C, Iliescu MG, Mihai MM, Popa LG, Stanescu AMA, Berteanu M. Botulinum Toxin Use for Modulating Neuroimmune Cutaneous Activity in Psoriasis. Medicina (Kaunas). 2022 Jun 16;58(6):813. doi: 10.3390/medicina58060813. — View Citation

Wallin EF, Hill DL, Linterman MA, Wood KJ. The Calcineurin Inhibitor Tacrolimus Specifically Suppresses Human T Follicular Helper Cells. Front Immunol. 2018 May 31;9:1184. doi: 10.3389/fimmu.2018.01184. eCollection 2018. — View Citation

Ward NL, Kavlick KD, Diaconu D, Dawes SM, Michaels KA, Gilbert E. Botulinum neurotoxin A decreases infiltrating cutaneous lymphocytes and improves acanthosis in the KC-Tie2 mouse model. J Invest Dermatol. 2012 Jul;132(7):1927-30. doi: 10.1038/jid.2012.60. Epub 2012 Mar 15. No abstract available. — View Citation

Wollina U, Tirant M, Vojvodic A, Lotti T. Treatment of Psoriasis: Novel Approaches to Topical Delivery. Open Access Maced J Med Sci. 2019 Aug 30;7(18):3018-3025. doi: 10.3889/oamjms.2019.414. eCollection 2019 Sep 30. — View Citation

Zhang Y, Zhang H, Jiang B, Yan S, Lu J. A promising therapeutic target for psoriasis: Neuropeptides in human skin. Int Immunopharmacol. 2020 Oct;87:106755. doi: 10.1016/j.intimp.2020.106755. Epub 2020 Jul 28. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the efficacy and safety of Mesobotox for treatment of plaque psoriasis as a monotherapy versus its combination with a topical Calcineurin inhibitor 0.03% ointment and topical Calcineurin inhibitor 0.03% ointment alone.	This will be evaluated by measuring the (Psoriasis severity (TES) score) which is a physician-based, four-point scoring system in which the thickness, erythema, and scales within each plaque will be rated from 0 (none) to 3 (severe) to evaluate the therapeutic outcome within different groups before and after treatment.	6 months
Secondary	To explore the treatment effects on the histopathological features of psoriasis.	Three millimeter-punch biopsy specimens will be obtained before treatment, under local anesthesia from each patient and after 2 months of treatment. The biopsy specimens will be preserved in 10% formalin solution. Histopathological evaluation of treatment response will be performed using Hematoxylin and Eosin (H&E) stain.	2 months
Secondary	To explore the treatment effects on the immunohistochemical features of psoriasis.	Immunohistochemical evaluation will be done using a special stain to detect SP before and 2 months after tratment.	2 months