Botulinum Toxin Blockade of Neuronal Signals to Immune Cells as a Novel Treatment for Hidradenitis Suppurativa
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- percent change from baseline in abscess and inflammatory nodule (AN) count and draining tunnel (dT) count
研究概览
简要总结
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..
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 13 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
placebo
Participants will be randomized 1:1 to receive placebo (saline) or botulinum toxin injections.
干预措施: Placebo (Drug)
botulinum toxin
Participants will be randomized 1:1 to receive placebo (saline) or botulinum toxin injections.
干预措施: Botulinum Toxin A (Allergan, Inc, Irvine CA) (Drug)
结局指标
主要结局
percent change from baseline in abscess and inflammatory nodule (AN) count and draining tunnel (dT) count
时间窗: 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
时间窗: 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
时间窗: 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).
次要结局
- Central sensitization Index(baseline and weeks 1, 12, 24)
- Hidradenitis Suppurativa Quality of Life(baseline and weeks 1, 12, 24)
- Dermatology Quality of Life Index(baseline and weeks 1, 12, 24)
- Numeric Rating Scale -30(baseline and weeks 1, 12, 24)
- Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA)(baseline and weeks 1, 12 ,24)
- Hidradenitis Suppurativa Clinical Response (HiSCR)-50(baseline and weeks 1, 12, 24)
- Hidradenitis Suppurativa Physician Global Assessment (HS-PGA)(baseline and weeks 1, 12, 24)
- International Hidradenitis Suppurativa Severity Score (IHS-4)(baseline and weeks 1, 12, 24)
- Hidradenitis Suppurativa Area and Severity Index Revised(baseline and weeks 1, 12, 24)
- Numeric Rating Scale - Itch(baseline and weeks 1, 12, 24)
- PainDETECT(baseline and weeks 1, 12, 24)
- Generalized Anxiety Disorder-7 (GAD-7)(baseline)
- Patient Health Questionnaire-9 (PHQ-9)(baseline and weeks 1, 12, 24)
- Central sensitization Index (CSI)(baseline and weeks 1, 12, 24)
- Hidradenitis Suppurativa Quality of Life (HiSQOL)(baseline and weeks 1, 12, 24)
研究者
Sarah Whitley
Assistant Professor of Dermatology
University of Massachusetts, Worcester