Botulinum Toxin Blockade of Neuronal Signals to Immune Cells as a Novel Treatment for Hidradenitis Suppurativa (Botox in HS)

This study will build on data from mice and humans implicating TRPV1 nociceptors in the pathogenesis of the type-17 chronic inflammatory skin disease hidradenitis suppurativa (HS). In this study, the investigators will extend data from a 12-week pilot study to rigorously test the hypothesis that botulinum toxin (BoNT) therapy reduces disease severity and relieves HS pain symptoms..

Study Overview

• Status: Not yet recruiting
• Conditions: Hidradenitis Suppurativa (HS)
• Intervention / Treatment: Drug: Placebo; Drug: Botulinum Toxin A (Allergan, Inc, Irvine CA)

Detailed Description

This study will recruit 40 HS patients with an abscess and inflammatory nodule (AN) count ≥5 at a single body site (ex. bilateral axillae, medial thighs). Participants will be randomized 1:1 to receive placebo or 50U of BoNT per 100cm2 of skin (100U total) administered twice over a 6-month study period. Randomization will be stratified by disease stage (Hurley stage <III, III). At baseline and weeks 4, 12, and 24 disease activity and pain symptom burden will be measured using percent change from baseline in abscess and inflammatory nodule (AN) count and draining tunnel (dT) count as primary outcomes and achievement of ≥ 30% reduction from baseline in the Patient's Global Assessment of Skin Pain Numeric Rating Scale (NRS)-30 as a secondary outcome. The investigators will conduct high-frequency ultrasound measurement of HS tunnel area at baseline and weeks 4,12, and 24 to determine if BoNT therapy can reduce tunnel size. The study team will also collect punch biopsies of lesional skin from HS patients before, and 4 weeks after BoNT treatment then perform flow cytometric, transcriptomic, and microscopic analysis of skin to determine if and how nonselective inhibition of neuropeptide release diminishes HS inflammation.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sarah K Whitley, MD, PhD; Phone Number: 508-856-4086; Email: sarah.whitley@umassmed.edu
• Study Contact Backup: Name: Terrie LaMarche; Email: terrie.lamarche@umassmed.edu

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • UMASS Chan Medical School
      • Contact: Deborah White; Phone Number: (508)856-2664; Email: deborah.white@umassmed.edu
      • Contact: Sidney Leno, MD; Phone Number: 714-455-4087; Email: sidney.leno@umassmed.edu
      • Principal Investigator: Sarah K Whitley, MD, PhD
      • Sub-Investigator: Jessica St. John, MD, MPH
      • Sub-Investigator: Sidney Leno, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >13 and <75
• established diagnosis of HS
• HS skin lesions of duration at least 1 year
• HS lesions in at least two distinct body areas
• inadequate response to a trial of an oral antibiotic or exhibited recurrence after discontinuation of antibiotics
• abscess and nodule (AN) count ≥ 5 at baseline
• draining tunnel count of <20 at baseline
• ability to provide written informed consent and/or assent

Exclusion Criteria:

• pregnant or breastfeeding
• history of neuromuscular disorder (ex. ALS, myasthenia gravis, Lambert-Eaton syndrome, myopathy
• medical co-morbidity ex. end stage congestive heart failure or coagulopathy that is a relative contradiction to skin biopsy procedure
• received systemic steroids or started a new systemic (biologic or non-biologic immunomodulator, oral retinoid) therapy with potential therapeutic impact for HS <12 weeks prior to baseline visit
• use of opioid or non-opioid oral analgesics within 14 days of baseline visit (exception: at a stable dose for at least 14 days prior to baseline)
• receiving anti-IL-17A/F, anti-IL-23, or anti-IL-1 biologic therapy or oral JAK inhibitor, TYK inhibitor
• active COVID-19 infection or history of COVID-19 infection within 4 weeks prior to baseline
• oral or IV antibiotic use during the treatment period (exception: stable dose of doxycycline or minocycline upto 100mg PO BID for 28 days prior to baseline and throughout the 6 month treatment and observation period
• initiation of topical therapies for HS within 14 days or baseline visit (may continue stable use of topical therapies started > 14 days prior to baseline visit), -laser surgery, laser hair removal, or elective surgery to treatment areas within 4 weeks prior to baseline visit
• current participation in another clinical study involving the administration of an investigative drug for the treatment of HS, or prior participation in such a study within 60 days prior to baseline visit,
• active bacterial, fungal, or viral infection in the treatment area at baseline visit, -immunocompromised state
• known hypersensitivity to botulinum toxin A preparations or any of their components (human albumin, saline, lactose, sodium succinate).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; Participants will be randomized 1:1 to receive placebo (saline) or botulinum toxin injections.	Drug: Placebo; 10 injections of 0.1mL of normal saline vehicle per laterality; Other Names: saline
Active Comparator: botulinum toxin; Participants will be randomized 1:1 to receive placebo (saline) or botulinum toxin injections.	Drug: Botulinum Toxin A (Allergan, Inc, Irvine CA); 50U per axilla in 10 injections of 0.1mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percent change from baseline in abscess and inflammatory nodule (AN) count and draining tunnel (dT) count	All subjects will receive 2 treatments with onabotulinum toxin A OR placebo (saline) 3 months apart, over a 6-month study period. At baseline and at week 12 each patient will receive 50 units of Botox per 100cm2 of skin, injected intradermally in 10 injections of 0.1mL spaced 1 cm apart to one HS-affected body site (ex. bilateral axillae, inguinal, medial thighs, inframammary chest) for a total of 100U per treatment.	baseline and weeks 4, 12, and 24
Microscopy Analyses of Skin Lesions	The study team will perform punch biopsies of lesions and non-lesional skin and perform direct immunohistochemistry and immunofluoresce microscopy analysis	baseline and day 7
Ultrasound monitoring of skin lesions	Ultra-high frequency ultrasound (UHFU): This non- invasive imaging technique will be used to quantify HS tunnel area and cutaneous blood flow rate in treatment areas using an established protocol as detailed in Oranges T Skin Res Technology 2020).	baseline and weeks 1, 12, 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dermatology Quality of Life Index	Assesses the degree of pain, the number of flares, and the impact on daily life . Dermatology disease agnostic, not specific for HS	baseline and weeks 1, 12, 24
Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA)	Response is defined as at least a 2-point reduction in HS-IGA score relative to baseline.	baseline and weeks 1, 12 ,24
Central sensitization Index (CSI)	measures centrally processed pain signals. The participant scores each answer on a scale of 0 (never) to 4 (always). A score of more than 40 indicates the presence of central sensitization.	baseline and weeks 1, 12, 24
Numeric Rating Scale -30	The numeric rating scale (NRS) is a pain scale that asks a patient to rate their pain on a scale of 0 to 10 where a higher score indicates a higher pain level. It's a common tool used in healthcare to assess pain severity.	baseline and weeks 1, 12, 24
Hidradenitis Suppurativa Clinical Response (HiSCR)-50	defined as a 50% reduction in inflammatory lesion count (abscesses + inflammatory nodules) with no increase in abscesses or draining fistulas when compared with baseline.	baseline and weeks 1, 12, 24
Hidradenitis Suppurativa Physician Global Assessment (HS-PGA)	The six-point Hidradenitis Suppurativa Physician Global Assessment (PGA) ranges from clear to very severe where a higher score indicates more severe disease. It is used in clinical trials to measure clinical improvement in inflammatory nodules,abscesses and draining fistulae	baseline and weeks 1, 12, 24
Hidradenitis Suppurativa Quality of Life (HiSQOL)	A 17-item questionnaire designed to measure quality of life for people with HS. Scores range from 0-68 where higher scores indicate a worse impact on quality of life.	baseline and weeks 1, 12, 24
International Hidradenitis Suppurativa Severity Score (IHS-4)	The International Hidradenitis Suppurativa Severity Score (IHS4) is a validated tool that measures the severity of hidradenitis suppurativa (HS). The IHS4 score is calculated by adding the number of nodules, abscesses, and draining tunnels, each multiplied by a weight A score of 3 or less indicates mild HS, 4-10 indicates moderate HS, and 11 or higher indicates severe HS. The IHS4 is used to assess the severity of HS and to measure inflammatory lesions, such as draining tunnels.	baseline and weeks 1, 12, 24
Hidradenitis Suppurativa Area and Severity Index Revised	The HASI-R method assesses HS severity in a manner that incorporates signs of inflammation and body surface area involved. Scores range from 0-720 where a higher score indicates worse disease.	baseline and weeks 1, 12, 24
Numeric Rating Scale - Itch	rates itch score as 1-10, 10 indicating most severe itch. similar to NRS pain instrument	baseline and weeks 1, 12, 24
PainDETECT	an assessment tool for neuropathic pain. Scores range from -1 to 38. A score of 19 or higher indicates neuropathic pain is likely.	baseline and weeks 1, 12, 24
Generalized Anxiety Disorder-7 (GAD-7)	The GAD-7 (General Anxiety Disorder-7) measures severity of anxiety over a 2 week period. Answers are scored from 0 to 3 ("not at all" = 0, "several days" = 1, "more than half the days" = 2, and "nearly every day"=3). A score of 10 or higher is considered positive for anxiety.	baseline
Patient Health Questionnaire-9 (PHQ-9)	The PHQ-9 (Patient Health Questionnaire-9) objectifies and assesses degree of depression severity via questionnaire. Nine questions indicate how often the symptom occurred over a 2-week period. A score of 10 or higher is considered clinically significant.	baseline and weeks 1, 12, 24

Collaborators and Investigators

• Sponsor: University of Massachusetts, Worcester
• Collaborators: Emory University
• Investigators: Principal Investigator: Sarah K Whitley, MD, PhD, UMASS Chan Medical School

Publications and helpful links

General Publications

• Kimball AB, Sobell JM, Zouboulis CC, Gu Y, Williams DA, Sundaram M, Teixeira HD, Jemec GB. HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study. J Eur Acad Dermatol Venereol. 2016 Jun;30(6):989-94. doi: 10.1111/jdv.13216. Epub 2015 Jul 22.
• Campanati A, Martina E, Giuliodori K, Bobyr I, Consales V, Offidani A. Two cases of Hidradenitis suppurativa and botulinum toxin type a therapy: A novel approach for a pathology that is still difficult to manage. Dermatol Ther. 2019 May;32(3):e12841. doi: 10.1111/dth.12841. Epub 2019 Feb 10.
• Grimstad O, Kvammen BO, Swartling C. Botulinum Toxin Type B for Hidradenitis Suppurativa: A Randomised, Double-Blind, Placebo-Controlled Pilot Study. Am J Clin Dermatol. 2020 Oct;21(5):741-748. doi: 10.1007/s40257-020-00537-9.
• Shih T, Lee K, Seivright JR, De DR, Shi VY, Hsiao JL. Hyperhidrosis treatments in hidradenitis suppurativa: A systematic review. Dermatol Ther. 2022 Jan;35(1):e15210. doi: 10.1111/dth.15210. Epub 2021 Nov 30.
• Campanati A, Martina E, Giuliodori K, Consales V, Bobyr I, Offidani A. Botulinum Toxin Off-Label Use in Dermatology: A Review. Skin Appendage Disord. 2017 Mar;3(1):39-56. doi: 10.1159/000452341. Epub 2017 Feb 1.
• Kim YS, Hong ES, Kim HS. Botulinum Toxin in the Field of Dermatology: Novel Indications. Toxins (Basel). 2017 Dec 16;9(12):403. doi: 10.3390/toxins9120403.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: August 4, 2026
• First Submitted That Met QC Criteria: August 4, 2026
• First Posted (Actual): August 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: ultrasound; botulinum toxin; Botox; tunnel area; mechanistic
• Additional Relevant MeSH Terms: Infections; Skin Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Sweat Gland Diseases; Skin Diseases, Bacterial; Skin Diseases, Infectious; Suppuration; Hidradenitis; Skin and Connective Tissue Diseases; Hidradenitis Suppurativa; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Hydrolases; Enzymes; Enzymes and Coenzymes; Inorganic Chemicals; Chlorine Compounds; Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Metalloproteases; Bacterial Proteins; Bacterial Toxins; Toxins, Biological; Sodium Compounds; Chlorides; Hydrochloric Acid; Botulinum Toxins, Type A; Sodium Chloride
• Other Study ID Numbers: STUDY00003339; 1R61AR087105-01A1 (Other Grant/Funding Number: NIAMS/NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Research team will share data and samples from this study with other investigators who are interested in skin diseases, but in that case no patient identifying information will be shared.
• IPD Sharing Time Frame: starting at time of publication of results, ending 7 years following study endpoint
• IPD Sharing Access Criteria: Proposals should be directed to sarah.whitley@umassmed.edu.To gain access to data, requesters will have to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No