Clinical trial NCT04508374: Intralesional Diode Laser Treatment of Fistulas in Hidradenitis Suppurativa
Official title: Intralesional Diode Laser Treatment of Fistulas in Hidradenitis Suppurativa: Protocol for a Within-person Randomised Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hidradenitis Suppurativa
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
First posted: 2020-08-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study is designed as a randomised, contralaterally-controlled, within-person design, where HS patients are randomised to undergo intralesional laser fibre treatment of HS tunnels in either right or left side of the body, whereas the other tunnel is left as an untreated control.
Primary purpose: TREATMENT

Brief summary: Hidradenitis suppurativa (HS) is a common chronic skin disease where patients experience inflamed painful nodules and chronic suppurating tunnels under the skin that often leave mutilating scars. Symptoms typically begin during adolescence and patients struggle with pain, pruritus, malodor and purulent discharge compromising work life, physical exercise, and sexual habits. Consequently, the risk of social exclusion, anxiety, depression, and suicide is increased among patients suffering from HS.

Creams, tablets, and injections aim to gain disease control, yet are sometimes not sufficient. Once HS tunnels have formed, surgical intervention is often required.

Recently, emergence of flexible diode laser fibers has enabled treatment of tunnels from within. The technique has been tested for perianal tunnels and in few studies also for HS tunnels with promising results. Overall, the laser fiber technique is still new, and knowledge of optimal treatment settings is sparse. However, there is reason to believe that intralesional laser fiber treatment of HS tunnels may provide a new tissue-sparing alternative to conventional surgical techniques with a potential to produce fewer side effects, less scaring, shorter downtime after surgery and possibly, also improved inflammatory control.

This study aims to investigate the efficacy and safety of laser fiber treatment of HS tunnels.

Method The project is carried out at the Dermatological Department, Roskilde University Hospital under the leadership of principal investigator Professor DmSc Gregor Jemec.

A prospective cohort study of intralesional laser fiber treatment of HS fistulas is planned.

After signing informed consent, patients with two comparable HS tunnels in typical areas will draw lot to receive experimental laser fiber treatment of one tunnel while the other tunnel serve as control. Efficacy will be monitored by pain scores, ultrasound, clinical photos, clinical measures of disease activity, quality-of-life scores, and skin biopsies. Patients will be followed 2, 6, 12 weeks and if possible, also 52 weeks after treatment. After 12 weeks, patients will be offered laser fiber treatment or standard of care surgery to the untreated control tunnel.

Detailed description: Background and aim:

Hidradenitis suppurativa (HS) is a common chronic skin disease that manifests by intermittent flare-ups of inflamed painful nodules that often leave mutilating scars, chronic suppurating tunnels and a changed microbiome compared to normal skin. Symptoms typically begin during adolescence and patients struggle with pain, pruritus, malodor and purulent discharge compromising work life, physical exercise, and sexual habits. Consequently, the risk of social exclusion, anxiety, depression and suicide is increased among patients suffering from HS.

Topical and systemic medical treatments, e.g. in the form of antibiotics, vitamin A derivates, immune-modulatory drugs or biological therapies aim to control inflammation. Once fistulas have formed, surgical intervention is often required. Present surgical therapies comprise surgical deroofing where the fistulas are cut open and left to heal, removal of specific pathological structures by ablative laser surgery or complete surgical removal en bloc of affected HS skin followed by skin grafting.

Recently, emergence of flexible diode laser fibers has enabled intra-lesional laser treatments of fistulas and the technique has been applied for e.g. perianal fistulas. Two prospective and one retrospective cohort studies evaluated a total of 265 patients treated with 1470 nm laser fiber surgery for perianal fistulas, demonstrating primary healing with absence of symptoms after one treatment in 40% to 71% of patients, a median healing time of 5 weeks, and long-term closure beyond 12 months in 71% of patients6. Intralesional laser fiber treatment has also been tested in HS tunnels. One study of concomitant 630 nm laser fiber treatment and photodynamic therapy has demonstrated a significant reduction in hidradenitis severity score and complete response in 47 % of patients after one treatment session.

Intralesional flexible laser fibers have also been tested in the treatment of HS tunnels without concomitant photodynamic therapy. One study investigated four sessions of 1064 nm intralesional diode laser therapy performed in local anesthesia. In a total of 20 patients, a significant reduction of Sartorius score and improved quality of life was demonstrated. No patients experienced neither worsening of disease nor complete cure and adverse effects were mild and transient. It was proposed, that intralesional laser treatment may elicit a decontaminating as well as an denaturing effect. Histological evaluation of endo-venous 1470 nm laser fiber treatment have demonstrated uniform coagulation without carbonization. Overall, the intralesional laser fiber technique is still new, and knowledge of optimal laser wave lengths, energy levels, number of treatments and treatment intervals is sparse. In addition, little is known about laser-tissue interactions in vivo as well as in vitro. However, there is reason to believe that intralesional laser fiber treatment of HS tunnels may provide a new tissue-sparing alternative to conventional surgical techniques with a potential to produce fewer side effects, less scaring, shorter downtime after surgery and possibly, also improved inflammatory control.

This study aims to investigate the efficacy and safety of 1470 nm laser fiber treatment of HS tunnels and add new knowledge of the microbiota as well as of laser-tissue interactions by in vivo ultrasound and in vitro histology.

Methods:

Study execution:

The project will be carried out at the Dermatological Department, Roskilde University Hospital under the leadership of principal investigator Professor Gregor Jemec, MD, DMSc. Senior doctor Ditte Marie Lindhardt Saunte, MD, PhD and Medical Doctor Elisabeth Hjardem Taudorf MD, PhD will run the project in cooperation with the established research group at the department

Study design:

A prospective cohort study of intralesional laser fiber treatment of HS fistulas is planned. Demographic data and information regarding prior treatments for HS will be collected in standardized case-report forms.

After signing informed consent, patients with HS tunnels in typical areas will be enrolled. Patients who have at least two suitable tunnels in typical HS areas will be invited to participate in the randomised within-person design to receive experimental laser fibre treatment. Two comparable HS tunnels from each patient will be selected enabling a subsequent randomisation to receive treatment or to serve as an intra-individual control, respectively.

Intervention:

The experimental treatment consists of one session of thermal coagulation with intralesional 1470 nm diode laser fibre in the entire length of one HS tunnel after injection of local anaesthetics (Mepivacaine-adrenaline). Both ends of tunnels selected for laser treatment must be accessible from the skin surface to ensure treatment of the entire tunnel.

Eligibility criteria: Inclusion Criteria:

* Legally competent women and men
* aged 18 years or older
* Two appropriate HS fistulas

Exclusion Criteria:

* fistulas in areas that have previously received surgery
* Allergy to lidocaine or adrenaline
* Fragile physical health that cannot tolerate standard of care HS rescue therapy
* Pregnant or lactating women

Primary outcomes:
measure: VAS pain
timeFrame: At baseline, 2, 6, and 12 weeks from baseline
Secondary outcomes:
measure: ultrasound
timeFrame: At baseline, and 12 weeks from baseline
measure: Blinded evaluation of improvement of left/right tunnel (yes/no) in clinical photographs
timeFrame: At baseline, 2, 6 and 12 weeks post treatment
measure: Lesion count
timeFrame: At baseline, 2, 6 and 12 weeks post treatment
measure: Change in Patients global assessment (PtGA)
timeFrame: At baseline, 2, 6 and 12 weeks post treatment
measure: Change in Physician's global assessment (PGA)
timeFrame: At baseline, 2, 6 and 12 weeks post treatment
measure: Described number of flares
timeFrame: At baseline, 2, 6 and 12 weeks post treatment
measure: Number of treated and control tunnels acquiring rescue therapy
timeFrame: At baseline, 2, 6 and 12 weeks post treatment
measure: Suppuration
timeFrame: At baseline, 2, 6 and 12 weeks post treatment
Other outcomes:
measure: Changes in Microbiome by investigation of skin biopsies
timeFrame: At baseline and 6 weeks from baseline
measure: Thermography
timeFrame: At baseline, 2, 6, and 12 weeks from baseline
measure: Dermatology Life Quality index (DLQI) questionnaire
timeFrame: baseline
measure: Patient satisfaction: VAS
timeFrame: At 12 weeks from baseline
measure: Number of patient preferring the treatment tunnel over the control tunnel
timeFrame: At 12 weeks from baseline
measure: Descriptive histological appearance of HS-tunnels
timeFrame: At baseline and 6 weeks from baseline
Locations:
city: Roskilde
country: Denmark
facility: zealand University Hospital Roskilde
Study officials:
affiliation: Zealand University Hospital - Roskilde
name: Gregor BE Jemec, DmSc, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saunte DML, Jemec GBE. Hidradenitis Suppurativa: Advances in Diagnosis and Treatment. JAMA. 2017 Nov 28;318(20):2019-2032. doi: 10.1001/jama.2017.16691.
citation: Ring HC, Thorsen J, Saunte DM, Lilje B, Bay L, Riis PT, Larsen N, Andersen LO, Nielsen HV, Miller IM, Bjarnsholt T, Fuursted K, Jemec GB. The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls. JAMA Dermatol. 2017 Sep 1;153(9):897-905. doi: 10.1001/jamadermatol.2017.0904.
citation: Thorlacius L, Cohen AD, Gislason GH, Jemec GBE, Egeberg A. Increased Suicide Risk in Patients with Hidradenitis Suppurativa. J Invest Dermatol. 2018 Jan;138(1):52-57. doi: 10.1016/j.jid.2017.09.008. Epub 2017 Sep 20.
citation: Terzi MC, Agalar C, Habip S, Canda AE, Arslan NC, Obuz F. Closing Perianal Fistulas Using a Laser: Long-Term Results in 103 Patients. Dis Colon Rectum. 2018 May;61(5):599-603. doi: 10.1097/DCR.0000000000001038.
citation: Wilhelm A, Fiebig A, Krawczak M. Five years of experience with the FiLaC laser for fistula-in-ano management: long-term follow-up from a single institution. Tech Coloproctol. 2017 Apr;21(4):269-276. doi: 10.1007/s10151-017-1599-7. Epub 2017 Mar 7.
citation: Giamundo P, Esercizio L, Geraci M, Tibaldi L, Valente M. Fistula-tract Laser Closure (FiLaC): long-term results and new operative strategies. Tech Coloproctol. 2015 Aug;19(8):449-53. doi: 10.1007/s10151-015-1282-9. Epub 2015 Feb 28.
citation: Suarez Valladares MJ, Eiris Salvado N, Rodriguez Prieto MA. Treatment of hidradenitis suppurativa with intralesional photodynamic therapy with 5-aminolevulinic acid and 630nm laser beam. J Dermatol Sci. 2017 Mar;85(3):241-246. doi: 10.1016/j.jdermsci.2016.12.014. Epub 2016 Dec 19.
citation: Fabbrocini G, Franca K, Lotti T, Marasca C, Annunziata MC, Cacciapuoti S, Masara A, Romanelli M, Lotti J, Wollina U, Tchernev G, Zerbinati N. Intralesional Diode Laser 1064 nm for the Treatment of Hidradenitis Suppurativa: A Report of Twenty Patients. Open Access Maced J Med Sci. 2018 Jan 7;6(1):31-34. doi: 10.3889/oamjms.2018.045. eCollection 2018 Jan 25.