Study on the Effectiveness of Hypothermal Sulphurous Water in Wound Hygiene

NCT06725797 | Enrolling By Invitation

• 2 other identifiers: VULNOLOGIATERMALE1AR12419075FF92A2
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an interventional double arms pilot study on the effectiveness of hydrogen sulfide (H2S) rich and microbiologically pure spa sulphurous water, in the wound hygiene of hard-to heal wounds, set in an italian spa facility. At least 24 subjects enrolled according to selection criteria will be 1:1 randomized in two intervention groups: the former (A) undergoing pack of sulphurous water on soaked gauzes for 20 minutes, the latter (B) undergoing full limb immersion for 20 minutes. Differences among the two arms will be assessed as changes in wound microbiome, wound pH, Trans epidermal water loss (TEWL), 1000x ex-vivo microscope imaging, wound fluorescence imaging for bacterial colonization and longitudinal shifts in wound sizing and peculiar features according to the Bates-Jensen Wound Assessment Tool (BWAT). Time required for re-epithelization will be recorded together with any adverse reactions or events for both arms and compared. The study aims at assessing the effectiveness of hydrogen sulfide exogenous supply on infected or colonized hard to heal wounds and which way of administration (pack Vs immersion) could have prevailing effects.

Conditions

Ulcers; Wound - in Medical Care; Wounds and Injuries; Wound Healing; Wound Care; Venous Ulcers; Wound Cleansing

Keywords

wound hygiene; chronic wound; sulfurous water; spa thermal water; wound care

Outcome Measures

Primary Outcomes (4)

• wound healing rate

  Longitudinal Wound healing rate will be assessed at each dressing change by applying Bates Jansen Wound Tool Score (BWAT)., max score 65, min 13, The HIGHER the total score, the more severe the wound status.

  within 10 minutes after wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)

• Short term Wound bacteria critical colonization

  The fluorescence wound imaging using Moleculight device, assessing critical bacterial colonization (\>104UFC) of the wound before intervention will be compared to that obtained after intervention to determine whether 20 minutes exposure to sulphurous water could have exerted an antibacterial activity. The HIGHER the luminescence, the more severe the wound critical colonization

  within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)

• Short term Wound microbiome changes

  Wound microbiome changes will be determined before treatment, immediately after the wound hygiene in order to assess its variation related to sulfurous hypothermal water exposure .(analysis of 16S ribosomial rNa sub-unit)

  within 10 minutes before and within 10 minutes after wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)

• Short Term Wound bed pH changes

  Ph of the wound bed will be measured using a flat glass cleavable probe, before and after intervention in order to detect if 20 minutes exposure to soaked gauzes in H2S rich water are enough to determine a lowering in wound pH values.(according to pH scale 0 to 10)

  within 10 minutes before and within 10 minutes after wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)

Secondary Outcomes (5)

• Longitudinal Wound microbiome changes during treatment up to re-epithelization

  within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)

• Longitudinal Wound bacterial critical colonization control

  within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)

• Longitudinal Wound bed pH changes

  within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)

• Longitudinal Wound TEWL changes

  within 10 minutes before wound hygiene, each session, every 48 hours, from day 0 up to wound re-epithelialization (up to 1 year)

• Long term re-epithelization stability

  90 days after wound healing (Tf)

Other Outcomes (4)

• Microbiological wound sampling

  at enrollment, day 0

• Effects of H2S rich water on wound biofilm integrity

  within 10 minutes before and within 10 minutes after wound hygiene, each session, every 48 hours from day 0 up to wound re-epithelialization (up to 1 year)

• Short term differences among the two arms: administration of H2S could impact on the effectiveness of re-epithelization

  within 10 minutes before and within 10 minutes after wound hygiene, each session, every 48 hours from day 0 up to wound re-epithelialization (up to 1 year)

Study Arms (2)

GROUP A:wound hygiene with spa thermal sulphurous water delivered with pack on soaked gauzes

ACTIVE COMPARATOR

non woven gauzes will be soaked with sulphurous thermal water and positioned on the wound as packs for 20 minutes, at spring temperature (23°C).

Procedure: wound hygiene with hypothermal sulfurous water by packs

GROUP B: limb full immersion in spa thermal sulphurous water

ACTIVE COMPARATOR

full wound immersion: the limb hosting the wound is located in a limb-sized tube filled with sulphurous water for 20 minutes at spring temperature (23°C).

Procedure: wound hygiene with hypothermal sulfurous water by limb full immersion

Interventions

wound hygiene with hypothermal sulfurous water by packs PROCEDURE

GROUP A: After dressing removal, the wound is exposed. Sulphur thermal water at spring temperature (23°C) is applied for 20 minutes on the untreated wound by packs on non woven gauzes entirely covering the area. Eventually, if dried, gauzes are externally watered with additional sulphurous thermal water during the 20 minutes. After water application the wound follows the other 3 steps of the wound hygiene protocol: non viable tissue removal, edges reactivation and dressing. Non interactive dressings, just for wound moisture management, are used on cleaned wound/s. Dressing fixation, elastic bandages or off-load will be provided when required. the intervention will be repeated every 48 hours for both arms.

Also known as: wound hygiene by packs

GROUP A:wound hygiene with spa thermal sulphurous water delivered with pack on soaked gauzes

wound hygiene with hypothermal sulfurous water by limb full immersion PROCEDURE

GROUP B: After dressing removal, the wound is exposed. Sulphur thermal water at spring temperature (23°C) is applied for 20 minutes on the untreated wound by limb full immersion in a limb tub. After the immersion, the wound follows the other 3 steps of the wound hygiene protocol: non viable tissue removal, edges reactivation and dressing. Non interactive dressings, just for wound moisture management, are used on cleaned wound/s. Dressing fixation, elastic bandages or off-load will be provided when required. the intervention will be repeated every 48 hours for both arms.

Also known as: wound hygiene by limb full immersion

GROUP B: limb full immersion in spa thermal sulphurous water

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \>18 years old
• Any comorbidities (except very severe I, II immune deficiencies)
• Any systemic drug therapy
• Any associated dressing (except peroxides)
• Acute or chronic wounds requiring wound care treatment
• Genital/oral wounds
• Infected wounds, including MDR pathogens
• Biofilmed wounds

You may not qualify if:

• Unexplored fistula
• Enteric fistula
• Exposure of fascia, vessels, bones, organs
• Pyoderma Gangrenosum (monotherapy)
• Implanted or penetrating devices (CVC , Port-a-cath, drainages, peritoneal dialysis, external fixators....etc.)
• Exposed implants(nails, plates, internal defibrillator, Pace maker)
• Local antibiotic therapy (not supported by antibiogram)

Sponsors & Collaborators

• University of Roma La Sapienza: lead
• Università degli studi di Roma Foro Italico: collaborator

Study Sites (1)

Terme di Roma Acque Albiule

Bagni di Tivoli, Rome, 00019, Italy

Location

Related Publications (20)

• Tsuji, Hideo.

  BACKGROUND

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  PMID: 22344563 BACKGROUND

• Davidelli S, Bassetto F, Vitale M, Scapagnini G. Thermal Waters and the hormetic effects of hydrogen Sulfide on inflammatory arthritis and wound healing. Chapter 10 elsevier https://www.sciencedirect.com/science/article/pii/B9780128142530000103

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  PMID: 36982430 BACKGROUND

• Ahmad A, Druzhyna N, Szabo C. Effect of 3-mercaptopyruvate Sulfurtransferase Deficiency on the Development of Multiorgan Failure, Inflammation, and Wound Healing in Mice Subjected to Burn Injury. J Burn Care Res. 2019 Feb 20;40(2):148-156. doi: 10.1093/jbcr/irz007.

  PMID: 30649358 BACKGROUND

• Benedetti F, Curreli S, Krishnan S, Davinelli S, Cocchi F, Scapagnini G, Gallo RC, Zella D. Anti-inflammatory effects of H2S during acute bacterial infection: a review. J Transl Med. 2017 May 10;15(1):100. doi: 10.1186/s12967-017-1206-8.

  PMID: 28490346 BACKGROUND

• Sheng L, Zhang Z, Zhang Y, Wang E, Ma B, Xu Q, Ma L, Zhang M, Pei G, Chang J. A novel "hot spring"-mimetic hydrogel with excellent angiogenic properties for chronic wound healing. Biomaterials. 2021 Jan;264:120414. doi: 10.1016/j.biomaterials.2020.120414. Epub 2020 Sep 19.

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• Han X, Wang L, Shang Y, Liu X, Yuan J, Shen J. Hydrogen sulfide-releasing polyurethane/gelatin/keratin-TA conjugate mats for wound healing. J Mater Chem B. 2022 Nov 3;10(42):8672-8683. doi: 10.1039/d2tb01700h.

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• Wu J, Chen A, Zhou Y, Zheng S, Yang Y, An Y, Xu K, He H, Kang J, Luckanagul JA, Xian M, Xiao J, Wang Q. Novel H2S-Releasing hydrogel for wound repair via in situ polarization of M2 macrophages. Biomaterials. 2019 Nov;222:119398. doi: 10.1016/j.biomaterials.2019.119398. Epub 2019 Aug 16.

  PMID: 31487582 BACKGROUND

• Wu J, Li Y, He C, Kang J, Ye J, Xiao Z, Zhu J, Chen A, Feng S, Li X, Xiao J, Xian M, Wang Q. Novel H2S Releasing Nanofibrous Coating for In Vivo Dermal Wound Regeneration. ACS Appl Mater Interfaces. 2016 Oct 19;8(41):27474-27481. doi: 10.1021/acsami.6b06466. Epub 2016 Oct 7.

  PMID: 27504858 BACKGROUND

• Zhang Y, Yue T, Gu W, Liu A, Cheng M, Zheng H, Bao D, Li F, Piao JG. pH-responsive hierarchical H2S-releasing nano-disinfectant with deep-penetrating and anti-inflammatory properties for synergistically enhanced eradication of bacterial biofilms and wound infection. J Nanobiotechnology. 2022 Jan 29;20(1):55. doi: 10.1186/s12951-022-01262-7.

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• Cremonini, V., Giuliani, R., Fusaroli, P., & Rubbi, I. Valutazione e monitoraggio delle ferite difficili con l'utilizzo della scala Bates-Jensen Assessment Tool: studio osservazionale. - DERMATOLOGICAL EXPERIENCES 2017;19:1-2. DOI: 10.23736/S1128-9155.17.00446-0

  BACKGROUND

• Pinnagoda J, Tupker RA, Agner T, Serup J. Guidelines for transepidermal water loss (TEWL) measurement. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis. 1990 Mar;22(3):164-78. doi: 10.1111/j.1600-0536.1990.tb01553.x.

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• Schneider LA, Korber A, Grabbe S, Dissemond J. Influence of pH on wound-healing: a new perspective for wound-therapy? Arch Dermatol Res. 2007 Feb;298(9):413-20. doi: 10.1007/s00403-006-0713-x. Epub 2006 Nov 8.

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• Wilson IA, Henry M, Quill RD, Byrne PJ. The pH of varicose ulcer surfaces and its relationship to healing. Vasa. 1979;8(4):339-42. No abstract available.

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• Toriyama T, Kumada Y, Matsubara T, Murata A, Ogino A, Hayashi H, Nakashima H, Takahashi H, Matsuo H, Kawahara H. Effect of artificial carbon dioxide foot bathing on critical limb ischemia (Fontaine IV) in peripheral arterial disease patients. Int Angiol. 2002 Dec;21(4):367-73.

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• Zhao H, Lu S, Chai J, Zhang Y, Ma X, Chen J, Guan Q, Wan M, Liu Y. Hydrogen sulfide improves diabetic wound healing in ob/ob mice via attenuating inflammation. J Diabetes Complications. 2017 Sep;31(9):1363-1369. doi: 10.1016/j.jdiacomp.2017.06.011. Epub 2017 Jun 30.

  PMID: 28720320 BACKGROUND

• Crucianelli, S., Fontana, M., Moretti, F., Cocomello, N., Mariano, A., & DEL BEN, M. (2024). PILOT STUDY ON THE EFFECTIVENESS OF SULFUROUS THERMAL WATER IN WOUND HYGIENE: SPA WOUND CARE. In The 24th Annual Meeting of the European Pressure Ulcer Advisory Panel Abstract book (pp. 81-81).

  RESULT

MeSH Terms

Conditions

Ulcer; Wounds and Injuries; Varicose Ulcer

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Varicose Veins; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Serena Crucianelli, MD

  La Sapienza University of Rome

  PRINCIPAL INVESTIGATOR

• Mario Fontana, MD, PhD

  La Sapienza University of Rome

  STUDY DIRECTOR

• Vincenzo Romano Spica, MD, PhD

  Foro Italico University of Rome

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Microbiological and microbiome assessors are blinded to subjects' treatment or arm randomization list. Epidemiological and statistic assessors are blinded to arm randomization list as well.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Associate Professor

Model Details: The study is an interventional pilot trial assessing the efficacy of hypothermal sulphurous thermal water (STW) in the wound hygiene of patients affected by hard to heal, chronic, infected wounds. The eligible subjects will be 1:1 randomized in two arms and treated with pure sulfurous spa water, already authorized for medical drinking therapy, on soaked gauzes (GROUP A) or for full limb immersion (GROUP B) for 20 minutes. Ph, Trans epidermal water loss (TEWL), healing rate (Bates-Jensen Wound Assessment Tool) wound fluorescence imaging for bacterial colonization and wound microbiome will be tested at 3 timepoints: T0 (prior treatment), T1 (just after treatment) , Tf (complete wound re-epithelization).

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: December 10, 2024
• Study Start: October 20, 2024
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)