Hidradenitis Suppurativa (HS)
Conditions
Keywords
botulinum toxin, Botox, ultrasound, tunnel area, mechanistic
Brief summary
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..
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.
Interventions
50U per axilla in 10 injections of 0.1mL
DRUGPlacebo
10 injections of 0.1mL of normal saline vehicle per laterality
Sponsors
University of Massachusetts, Worcester
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Interventional, phase 2, randomized, placebo-controlled clinical trial of botulinum toxin (BoNT) in patients with moderate to severe hidradenitis suppurativa (HS).
Eligibility
Sex/Gender
ALL
Age
13 Years to 75 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| percent change from baseline in abscess and inflammatory nodule (AN) count and draining tunnel (dT) count | baseline and weeks 4, 12, and 24 | 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. |
| Microscopy Analyses of Skin Lesions | baseline and day 7 | The study team will perform punch biopsies of lesions and non-lesional skin and perform direct immunohistochemistry and immunofluoresce microscopy analysis |
| Ultrasound monitoring of skin lesions | baseline and weeks 1, 12, 24 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA) | baseline and weeks 1, 12 ,24 | Response is defined as at least a 2-point reduction in HS-IGA score relative to baseline. |
| Central sensitization Index (CSI) | baseline and weeks 1, 12, 24 | 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. |
| Numeric Rating Scale -30 | baseline and weeks 1, 12, 24 | 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. |
| Hidradenitis Suppurativa Clinical Response (HiSCR)-50 | baseline and weeks 1, 12, 24 | defined as a 50% reduction in inflammatory lesion count (abscesses + inflammatory nodules) with no increase in abscesses or draining fistulas when compared with baseline. |
| Hidradenitis Suppurativa Physician Global Assessment (HS-PGA) | baseline and weeks 1, 12, 24 | 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 |
| Hidradenitis Suppurativa Quality of Life (HiSQOL) | baseline and weeks 1, 12, 24 | 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. |
| Dermatology Quality of Life Index | baseline and weeks 1, 12, 24 | Assesses the degree of pain, the number of flares, and the impact on daily life . Dermatology disease agnostic, not specific for HS |
| International Hidradenitis Suppurativa Severity Score (IHS-4) | baseline and weeks 1, 12, 24 | 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. |
| Hidradenitis Suppurativa Area and Severity Index Revised | baseline and weeks 1, 12, 24 | 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. |
| Numeric Rating Scale - Itch | baseline and weeks 1, 12, 24 | rates itch score as 1-10, 10 indicating most severe itch. similar to NRS pain instrument |
| PainDETECT | baseline and weeks 1, 12, 24 | an assessment tool for neuropathic pain. Scores range from -1 to 38. A score of 19 or higher indicates neuropathic pain is likely. |
| Generalized Anxiety Disorder-7 (GAD-7) | baseline | 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. |
| Patient Health Questionnaire-9 (PHQ-9) | baseline and weeks 1, 12, 24 | 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. |
Countries
United States
Contacts
CONTACTSarah K Whitley, MD, PhD
CONTACTTerrie LaMarche
PRINCIPAL_INVESTIGATORSarah K Whitley, MD, PhD
UMass Chan Medical School
Outcome results
None listed