Botulinum Toxin Blockade of Neuronal Signals to Immune Cells as a Novel Treatment for Hidradenitis Suppurativa

Phase 2Not Yet RecruitingNCT07756346

University of Massachusetts, Worcester40 enrolled

Overview

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..

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hidradenitis Suppurativa (HS)

Interventions

Botulinum Toxin A (Allergan, Inc, Irvine CA)DRUG

50U per axilla in 10 injections of 0.1mL

PlaceboDRUG

10 injections of 0.1mL of normal saline vehicle per laterality

Eligibility

Sex: ALLMin age: 13 YearsMax age: 75 Years

Medical Language ↔ Plain English

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).

Locations (1)

UMass Chan Medical School

Worcester, Massachusetts, United States

Outcomes

Primary Outcomes

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.

Time frame: 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

Time frame: 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).

Time frame: baseline and weeks 1, 12, 24

Secondary Outcomes

Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA)

Response is defined as at least a 2-point reduction in HS-IGA score relative to baseline.

Time frame: 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.

Time frame: baseline and weeks 1, 12, 24

Numeric Rating Scale -30

Central Contacts

Sarah K Whitley, MD, PhD

CONTACT

508-856-4086 sarah.whitley@umassmed.edu

Terrie LaMarche

CONTACT

terrie.lamarche@umassmed.edu

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.