Clinical trial NCT06109844: FORCEREPAIR - A Wound Exudate Investigation
Official title: FORCEREPAIR - A Wound Exudate Investigation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Venous Leg Ulcer
Wound Healing
Non-healing Wound
Cytokines
Keywords: Venous Leg Ulcer
Varicose Ulcer
Cytokines
Wound Exudate
Wound Healing
Wound Inflammation
Wound Microbiome
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: Akribes Biomedical GmbH
name: Vascular Research Unit and Department of Vascular Surgery
First posted: 2023-10-31
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Twenty patients with venous leg ulcers, verified by a wound expert, will be included in this study.

Brief summary: The observational longitudinal study will collect wound exudate from twenty patients with venous leg ulcers. Wound exudate samples are collected using twenty-four-hour collection with polyurethane foam, bandages and the NovaSwab method. Each patient is seen four times where wound exudate and the bacteria microbiome are sampled and wound size is monitored with advanced planimetric tools.

Detailed description: This dual centre longitudinal observational study will run from January 2024 to January 2025. The investigation will include twenty patients over four weeks including four study visits. Sampling of wound exudate can take place on every visit and will be made with the polyurethane discs, the NovaSwab technique and waste bandages. The wound bacteria microbiome is sampled with routine bacterial swabs. Tape strips will be used to assess perilesional skin and control sites of normal skin and will primarily measure skin inflammation parameters. Clinical pictures are taken and analysed using advanced planimetric tools. Patients enrolled receive standard wound care; allowing all kinds of dressing. However when consenting to twenty-four-hour-collection patients will not be allowed to wear active bandages or receive antibiotic treatment for that period. Compression, wound dressings, and use of topical and oral antibiotics will be registered. For the storage of samples, a research biobank is used, and leftover material will be stored in a biobank for future research.

Eligibility criteria: Inclusion Criteria:

* Adults fulfilling all inclusion criteria
* Age \>18 years
* Venous leg ulcer diagnosis and classic characteristics (localisation, varicose veins, brown-orange hyperpigmentation, leg oedema, stasis dermatitis, atrophie blanche or lipodermatosclerosis) verified by a wound expert (if in doubt venous doppler will be used for verification)
* Wound Area equal to or above 1 cm2 (measured with a ruler length x width)
* Patient can understand Danish
* Patient can comply with protocol
* Patient is fully informed about the study and has given informed consent

Exclusion Criteria:

* Venous leg ulcer with communication to bone
* Known or suspected cancer in the wound
* Allergies towards products used in the study, e.g. polyurethane foam and tegaderm
* Dementia
* Judgement by the investigator that the patient is not suited for study participation

Primary outcomes:
measure: Wound Exudate Effects on Proliferation of Healthy Primary Human Fibroblasts
timeFrame: Four weeks
measure: Wound Exudate Effects on Matrix Formation by Healthy Primary Human Fibroblasts
timeFrame: Four weeks
measure: Wound Exudate Effects on Release of Pro-inflammatory Mediators
timeFrame: Four weeks
measure: Wound Exudate Effects on Cellular Gene Expression Profiles In Healthy Primary Human Fibroblasts
timeFrame: Four weeks
measure: Exploratory Wound Exudate Compound and Device Testing
timeFrame: Four weeks
Secondary outcomes:
measure: Wound Exudate Profile Relation to Percentage Area Reduction
timeFrame: Four Weeks
measure: Wound Exudate Profile Relation to Wound Microbiome Profile
timeFrame: Four Weeks
measure: Percentage Area Reduction Relation to Wound Microbiome Profile
timeFrame: Four Weeks
measure: Comparisson of Wound Exudate Sampling Techniques
timeFrame: Four Weeks
measure: Wound Microbiome 16 rRNA/18sRNA
timeFrame: Four Weeks
measure: Wound Perilesional Skin Inflammation
timeFrame: Four Weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Danish Wound Healing Center, Bispebjerg Hospital
state: Northwest
city: Viborg
country: Denmark
facility: Vascular Research Unit and Department of Vascular Surgery, Viborg Regional Hospital
Study officials:
affiliation: Bispebjerg Hospital
name: Frederik Plum, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wolff-Winiski, Barbara, Anton Stütz, and Petra Dörfler. "Methods for identifying a non-healing skin wound and for monitoring the healing of a skin wound." U.S. Patent 11,579,141, issued February 14, 2023
citation: Burian EA, Sabah L, Karlsmark T, Kirketerp-Moller K, Moffatt CJ, Thyssen JP, Agren MS. Cytokines and Venous Leg Ulcer Healing-A Systematic Review. Int J Mol Sci. 2022 Jun 10;23(12):6526. doi: 10.3390/ijms23126526.
citation: Serra R, Grande R, Buffone G, Molinari V, Perri P, Perri A, Amato B, Colosimo M, de Franciscis S. Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines. Int Wound J. 2016 Feb;13(1):53-8. doi: 10.1111/iwj.12225. Epub 2014 Feb 19.
citation: Tomic-Canic M, Burgess JL, O'Neill KE, Strbo N, Pastar I. Skin Microbiota and its Interplay with Wound Healing. Am J Clin Dermatol. 2020 Sep;21(Suppl 1):36-43. doi: 10.1007/s40257-020-00536-w.
citation: Versey Z, da Cruz Nizer WS, Russell E, Zigic S, DeZeeuw KG, Marek JE, Overhage J, Cassol E. Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation. Front Immunol. 2021 Apr 9;12:648554. doi: 10.3389/fimmu.2021.648554. eCollection 2021.
citation: Misic AM, Gardner SE, Grice EA. The Wound Microbiome: Modern Approaches to Examining the Role of Microorganisms in Impaired Chronic Wound Healing. Adv Wound Care (New Rochelle). 2014 Jul 1;3(7):502-510. doi: 10.1089/wound.2012.0397.
citation: Wolcott RD, Hanson JD, Rees EJ, Koenig LD, Phillips CD, Wolcott RA, Cox SB, White JS. Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing. Wound Repair Regen. 2016 Jan-Feb;24(1):163-74. doi: 10.1111/wrr.12370. Epub 2015 Dec 10.
citation: Loesche M, Gardner SE, Kalan L, Horwinski J, Zheng Q, Hodkinson BP, Tyldsley AS, Franciscus CL, Hillis SL, Mehta S, Margolis DJ, Grice EA. Temporal Stability in Chronic Wound Microbiota Is Associated With Poor Healing. J Invest Dermatol. 2017 Jan;137(1):237-244. doi: 10.1016/j.jid.2016.08.009. Epub 2016 Aug 24.
citation: Trengove NJ, Bielefeldt-Ohmann H, Stacey MC. Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen. 2000 Jan-Feb;8(1):13-25. doi: 10.1046/j.1524-475x.2000.00013.x.
citation: Wiegand C, Bittenger K, Galiano RD, Driver VR, Gibbons GW. Does noncontact low-frequency ultrasound therapy contribute to wound healing at the molecular level? Wound Repair Regen. 2017 Sep;25(5):871-882. doi: 10.1111/wrr.12595. Epub 2017 Dec 8.
citation: Ambrosch A, Lobmann R, Pott A, Preissler J. Interleukin-6 concentrations in wound fluids rather than serological markers are useful in assessing bacterial triggers of ulcer inflammation. Int Wound J. 2008 Mar;5(1):99-106. doi: 10.1111/j.1742-481X.2007.00347.x. Epub 2008 Jan 3.
citation: Burian EA, Enevold C, Karlsmark T, Agren MS. A simplified method for monitoring cytokines in wound fluid. Wound Repair Regen. 2023 Jan;31(1):47-55. doi: 10.1111/wrr.13053. Epub 2022 Oct 26.