Clinical trial NCT06928246: The Impact of Botox on Neuroimmune Interactions in Atopic Dermatitis
Official title: Pilot Study on Cellular and Molecular Impact of Neuroimmune Interactions in Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Atopic Dermatitis (AD)
Keywords: Atopic dermatitis
Eczema
Botox
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Almirall, S.A.
First posted: 2025-04-15
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: The purpose of this study is to understand cellular and molecular interactions in the skin of participants with mild-to-moderate AD, and how botulinum toxin alters these interactions.

Detailed description: Atopic dermatitis is a debilitating chronic inflammatory disease with substantial health and economic impact, affecting 10-20% of the U.S. population with an estimated annual direct health care cost of $13 billion. There is much to still discover regarding the dysfunctional skin barrier underlying AD and its effects on quality of life, highlighting a critical health care cap. AD manifests as erythematous and pruritic plaques often in flexural regions of the body, but may also be widespread as well. AD patients suffer from high rates of mental health disorders and often report a poor quality of life (QoL).

The pathogenesis of AD is multifactorial, involving both genetic and environmental components. Specifically, a defect in the filaggrin gene is a common etiology. Moreover, it is thought that decreased levels of ceramides within the epidermis allow for an abnormal amount of transepidermal water loss leading to an increased Th2 response and subsequently, overexpression of proinflammatory cytokines IL-4 and IL-5. Additionally, scratching of the epidermis promotes increased levels of IL-1, IL-6 and TNF-alpha from keratinocytes.

The objective of this pilot study is to determine whether cutaneous neurons are required for the maintenance of atopic dermatitis (AD) lesions. The significance derives from the potential to reveal novel neuro-immune pathways that could provide suitable targets for future therapeutic approaches for this disease. Specifically, the investigators hypothesize that neurotransmitters released from cutaneous neurons are required for the persistence of AD lesions. This is supported by a prior report showing that injection of botulinum toxin which prevents vesicular fusion in neurons and hence neurotransmitter release led to clinical improvement and resolution of AD lesions. Similar findings have been reported with Psoriasis. The investigators approach will analyze biopsy samples from AD patients treated with botulinum toxin using spatial single cell imaging.

The project will be performed in 2 phases. Phase 1a will include a pilot run of spatial single cell imaging performed on normal skin and with atopic dermatitis. In Phase 1b, the investigators will administer intradermal botulinum toxin in AD lesions to determine the kinetics of the clinical response when neurotransmitter release is inhibited using standardized clinical outcome assessments, including Physician Global Assessment (PGA) and Eczema Area and Severity Index (EASI). The kinetics, or time, to reduction of lesion severity, as determined in Phase 1b, will be used in Phase 2 to determine the biopsy visits.

Phase 2 will test the hypothesis that botulinum toxin therapy alters the cellular and molecular state of AD lesions, specifically by blocking neuroimmune interactions with a specific emphasis of cytokine and chemokine interactions. In Phase 2, botulinum toxin will be injected into multiple lesions in a small cohort of AD patients. Based on the results of Phase 1b, skin biopsies will be harvested at 3 different times and analyzed using spatial single cell imaging.

It is expected that these experiments will implicate neuroimmune interactions in the pathogenesis of AD and serve as proof-of-concept for design of randomized controlled trials (RCTs) evaluating the efficacy of botulinum toxin to reduce inflammation, lesion severity, and improve quality of life for AD patients. Once patients are clear, inhibition of neurotransmitter release could be used to prevent recurrence thereby avoiding long-term immunosuppression and its associated risks.

Eligibility criteria: Inclusion Criteria:

Phase 1b:

* Patients 18 years or older at time of consent
* Mild-to-Moderate AD, defined as:
* BSA ≤ 10%
* IGA ≤ 3
* No past biologic therapy
* No systemic therapy for 3 months
* No topical therapy for treatment of AD for 4 weeks

Phase 2:

* Patients 18 years or older at time of consent
* Mild-to-Moderate AD, defined as:
* BSA ≤ 10%
* IGA ≤ 3
* At least one patch of eczema of at least 5 cm in diameter
* No past biologic therapy
* No systemic therapy for 3 months
* No topical therapy for treatment of AD for 4 weeks

Exclusion Criteria:

Phase 1b:

* Age less than 18 years old
* Pregnant or breastfeeding
* Has medical comorbidity such as end stage congestive heart failure or coagulopathy that is a relative contradiction to skin biopsy procedure
* Has had prior exposure to biologic treatments or has had prior treatment with systemic non-biologics (e.g. methotrexate) within 12 weeks
* Has used topical therapy for treatment of AD within 4 weeks

Phase 2:

* Patients enrolled in Phase 1
* Age less than 18 years old
* Pregnant or breastfeeding
* Has medical comorbidity such as end stage congestive heart failure or coagulopathy that is a relative contradiction to skin biopsy procedure
* Has had prior exposure to biologic treatments or has had prior treatment with systemic non-biologics (e.g. methotrexate) within 12 weeks
* Has used topical therapy for treatment of AD within 4 weeks

Primary outcomes:
measure: Percentage change in EASI scores at Day 28 as compared to baseline.
timeFrame: At Day 28
measure: Percentage change in PGA at Day 28 as compared to baseline.
timeFrame: At Day 28
Secondary outcomes:
measure: Percentage change in transcriptional mRNA in immune and non-immune cells in skin biopsies, up to Day 28, as compared to baseline.
timeFrame: Until last biopsy, up to Day 28
measure: Percentage change in spatial distribution of specific cell types in skin biopsies, up to Day 28, as compared to baseline.
timeFrame: Until last biopsy, up until Day 28
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Daniel Kaplan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.