Atopic Dermatitis (AD)Phase 1ADNCT06928246
The Impact of Botox on Neuroimmune Interactions in Atopic Dermatitis
A Phase 1 study testing Onabotulinum Toxin Type A - Phase 1b and Onabotulinum Toxin Type A - Phase 2 in people with Atopic Dermatitis (AD), run by Daniel Kaplan at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atopic Dermatitis (AD)
- What is being tested?
- Onabotulinum Toxin Type A - Phase 1b and Onabotulinum Toxin Type A - Phase 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Jul 2025to Jan 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 17Show fewer
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
UPMC Department of Dermatology
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Pilot Study on Cellular and Molecular Impact of Neuroimmune Interactions in Atopic Dermatitis
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.
Read the 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.
- Conditions
- Atopic Dermatitis (AD)
- Being tested
- Onabotulinum Toxin Type A - Phase 1b, Onabotulinum Toxin Type A - Phase 2
- Keywords
- Atopic dermatitis, Eczema, Botox
- Medical subject headings
- Dermatitis, Atopic, Eczema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Onabotulinum Toxin Type A - Phase 1bDrug
The lesions receiving Botulinum toxin will get five 0.1 mL intradermal injections of 5 units of Botulinum toxin which equates to 25 units per lesion and 50 units per patient.
Onabotulinum Toxin Type A - Phase 2Drug
The lesions receiving Botulinum toxin will get five 0.1 mL intradermal injections of 5 units of Botulinum toxin which equates to 25 units per lesion and 75 units per patient.
| Study group | Role | What they receive |
|---|---|---|
| Onabotulinum Toxin Type A - Phase 1b | Experimental | Onabotulinum toxin administered to two lesions. Receives: Drug: Onabotulinum Toxin Type A - Phase 1b |
| Onabotulinum Toxin Type A - Phase 2 | Experimental | Onabotulinum toxin administered to three lesions. Receives: Drug: Onabotulinum Toxin Type A - Phase 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage change in EASI scores at Day 28 as compared to baseline.
Eczema Area and Severity Index (EASI) total score from 0-72, with higher score indicating more severity. The EASI index assigns proportionate values to 4 body regions. Each region is assigned a score of 0 to 3, indicating none, mild, moderate, and severe clinical expression. The percentage of area involved is also assigned an eruption proportional score from 0 to 6. The total body score for each body region is obtained by multiplying the sum of the severity scores by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gives the EASI total from 0-72.
Measured: At Day 28
Percentage change in PGA at Day 28 as compared to baseline.
The Physician's Global Assessment (PGA) is a clinician-reported measure used to assess the overall severity of atopic dermatitis (AD) at a single time point. It utilizes a scale of 5-points; total scale ranging from 0 (clear) to 5 (severe disease). The PGA score represents overall disease severity based on clinical signs including erythema, induration/papulation, lichenification, and oozing/crusting. Higher scores indicate greater disease severity.
Measured: At Day 28
Secondary outcomes (2)
Percentage change in transcriptional mRNA in immune and non-immune cells in skin biopsies, up to Day 28, as compared to baseline.
Skin biopsies used to analyze transcriptional mRNA in immune and non-immune cells. Expression levels tested by Xenium Spatial Cell Imaging; a high-resolution, spatial transcriptomics platform used to perform single-cell resolution analysis of cell populations by mapping their gene expression profiles.
Measured: Until last biopsy, up to Day 28
Percentage change in spatial distribution of specific cell types in skin biopsies, up to Day 28, as compared to baseline.
Skin biopsies used to analyze spatial location of immune and non-immune cells. Expression levels tested by Xenium Spatial Cell Imaging; a high-resolution, spatial transcriptomics platform used to perform single-cell resolution analysis of cell populations by mapping their spatial distribution profiles.
Measured: Until last biopsy, up until Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2025
- Study start17 Jul 2025
- Primary completion15 Dec 2026 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atopic Dermatitis (AD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daniel Kaplan
- Sponsor type
- University, hospital or other
- Collaborators
- Almirall, S.A.
- Responsible party
- Sponsor-investigator, Daniel Kaplan, University of Pittsburgh
- Investigators
- Daniel Kaplan, MD, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06928246
- Sponsor's protocol ID
- STUDY24110067
- Acronym
- AD
- Status last verified
- May 2026
- First submitted
- 7 Apr 2025
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified IPD can be made available to researchers in a closed environment for a specified period of time.
Publications
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.
PubMed 35744076Khattab 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.
PubMed 32983334
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study on Cellular and Molecular Impact of Neuroimmune Interactions in Atopic Dermatitis
- ClinicalTrials.gov ID
- NCT06928246
- Acronym / sponsor ID
- AD / STUDY24110067
- Conditions
- Atopic Dermatitis (AD)
- Keywords
- Atopic dermatitis, Eczema, Botox
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- Daniel KaplanUniversity, hospital or other
- Collaborators
- Almirall, S.A.
- Study start
- 17 Jul 2025 (actual)
- Primary completion
- 15 Dec 2026 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 15 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Onabotulinum Toxin Type A - Phase 1b | Experimental | Drug: Onabotulinum Toxin Type A - Phase 1bOnabotulinum toxin administered to two lesions. |
| Onabotulinum Toxin Type A - Phase 2 | Experimental | Drug: Onabotulinum Toxin Type A - Phase 2Onabotulinum toxin administered to three lesions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients 18 years or older at time of consent
- Mild-to-Moderate AD, defined as:
- BSA ≤ 10%
- IGA ≤ 3
- No past biologic therapy
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Onabotulinum Toxin Type A - Phase 1bThe lesions receiving Botulinum toxin will get five 0.1 mL intradermal injections of 5 units of Botulinum toxin which equates to 25 units per lesion and 50 units per patient. | Drug | Onabotulinum Toxin Type A - Phase 1b |
| Onabotulinum Toxin Type A - Phase 2The lesions receiving Botulinum toxin will get five 0.1 mL intradermal injections of 5 units of Botulinum toxin which equates to 25 units per lesion and 75 units per patient. | Drug | Onabotulinum Toxin Type A - Phase 2 |
Primary outcome
Percentage change in EASI scores at Day 28 as compared to baseline.
Time frame: At Day 28
Eczema Area and Severity Index (EASI) total score from 0-72, with higher score indicating more severity. The EASI index assigns proportionate values to 4 body regions. Each region is assigned a score of 0 to 3, indicating none, mild, moderate, and severe clinical expression. The percentage of area involved is also assigned an eruption proportional score from 0 to 6. The total body score for each body region is obtained by multiplying the sum of the severity scores by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gives the EASI total from 0-72.
Percentage change in PGA at Day 28 as compared to baseline.
Time frame: At Day 28
The Physician's Global Assessment (PGA) is a clinician-reported measure used to assess the overall severity of atopic dermatitis (AD) at a single time point. It utilizes a scale of 5-points; total scale ranging from 0 (clear) to 5 (severe disease). The PGA score represents overall disease severity based on clinical signs including erythema, induration/papulation, lichenification, and oozing/crusting. Higher scores indicate greater disease severity.
2 secondary outcomes
Percentage change in transcriptional mRNA in immune and non-immune cells in skin biopsies, up to Day 28, as compared to baseline.
Time frame: Until last biopsy, up to Day 28
Percentage change in spatial distribution of specific cell types in skin biopsies, up to Day 28, as compared to baseline.
Time frame: Until last biopsy, up until Day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
- Background: PubMed 35744076Popescu 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.
- Background: PubMed 32983334Khattab 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.
- Individual participant dataSharing planned: Yes. De-identified IPD can be made available to researchers in a closed environment for a specified period of time.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Kaplan, MD, PhD principal investigator
University of Pittsburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Onabotulinum Toxin Type A - Phase 1b and Onabotulinum Toxin Type A - Phase 2 in people with Atopic Dermatitis (AD), run by Daniel Kaplan at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage change in EASI scores at Day 28 as compared to baseline. (time frame: At Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06928246, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.