Scar Formation
Conditions
Keywords
YAP1, Verteporfin, Scar, Fibrosis, Wound healing
Brief summary
When we get injured, our body naturally tries to heal. In adults, this healing often leads to scars - thick, stiff tissue known as fibrotic tissue. Unlike normal tissue, fibrotic tissue doesn't function properly and can cause serious health problems, depending on the affected organ. Once it forms, fibrosis is usually permanent. A good example of the fibrosis process is the healing of our skin: after a cut or surgery, the resulting scar is a type of fibrosis. Special cells called fibroblasts are key players in this process. Our study looks at a drug called verteporfin, which is already approved both in Europe and the U.S. Previous research on mice and human cells suggests it can reduce or even prevent fibrosis. We are now testing, clinically, histologically and by scRNA-seq, whether injecting verteporfin into the skin during wound healing, specifically after surgical procedures, can prevent thick, rigid scars from forming. Since the skin is easy to observe and sample, it offers a great model for studying this. Will verteporfin have an impact on how surgical wounds heal? That's what we aim to find out.
Interventions
DRUGNaCl (placebo)
During the safety margin excision, the placebo (NaCl) will be injected into the wound before suturing.
During the safety margin excision, the study drug (Verteporfin) will be injected into the wound before suturing.
Sponsors
University of Geneva, Switzerland
University Hospital, Geneva
Jöri Pünchera
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide informed consent as documented by signature * Age is \>/= 18 years and \< 56 years (differently said: starting from the 18th birthday to completion of their 55 years) * Indication for a safety margin excision (5 mm laterally) due to melanoma in situ or severe dysplastic nevi previously completely excised * Length of initial scar from 15 mm to 50 mm * The initial lesion was excised on the back (to ensure that all patients undergo their safety margin excision within the internationally accepted timeframe, we will also accept patients requiring the procedure at another anatomical site if a particular batch cannot be filled within 4 weeks of its first patient's enrollment)
Exclusion criteria
* Clinical adenopathy (cervical, axillar, inguinal) defined as a lymph node of more than 1 cm diameter * Melanoma in situ of lentigo maligna or acral lentiginous type * Head and neck location * Diameter of initial lesion above or equal to 3 cm * Known and documented hypersensitivity to Verteporfin or to any of its excipients: lactose monohydrate, egg phosphatidylglycerol (to simplify we will exclude patients with known and documented allergy to egg protein), dimyristoyl phosphatidylcholine, ascorbyl palmitate, butylated hydroxytoluene (E321) * Porphyria * Moderate hepatic dysfunction referred to as any of the following: AST \>1.2x upper normal range, ALT \>1.2x upper normal range, decreased albumin level, prolongation of PT * Biliary obstruction referred to as any of the following: ALP \>1.2x upper normal range, GGT \>1.2x upper normal range, anormal bilirubin level * Pregnancy referred to as: positive beta-hCG blood test * Breast-feeding * Planned pregnancy in the next 6 months * History of either one of the following: keloids, scleroderma, morphea, lupus erythematosus, nephrogenic systemic fibrosis, graft-versus-host disease, lichen sclerosus, eosinophilic fasciitis, Ehlers-Danlos syndrome, cutis laxa, Marfan syndrome, or pseudoxanthoma elasticum
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of the profibrotic mesenchymal fibroblast subpopulation in the study group compared to the placebo group. | There are 90 +/- 10 days between visit 1 and visit 4. | For comparison between groups, skin samples of the repaired tissue taken at visit 4 (Day 90 +/- 10) will be compared between the patients of both groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of pilosebaceous units and profibrotic activity (quantity of collagen I and III and its ratio, fibronectin, α-SMA, nuclear localization of YAP1 and En1-staining) and its change over time | There are 90 +/- 10 days between visit 1 and visit 4. | For comparison over time in both groups, skin samples of the repaired tissue taken at visit 4 (Day 90 +/- 10) will be compared to the scar sample of visit 1 (Day 0) in all patients of both groups. |
| Quantification of the different fibroblast subpopulations in unwounded, healthy skin. | The initial excision will take place 21 to 54 days before V1. | In all patients, 2 slices of the initial FFPE skin samples will be analyzed. |
| The changes of fibroblast subpopulations, clusters, and their different cell-cell interactions in both groups before and after the study intervention. | There are 90 +/- 10 days between visit 1 and visit 4. | For comparison over time in both groups, skin samples of the repaired tissue taken at visit 4 (Day 90 +/- 10) will be compared to the scar sample of visit 1 (Day 0) in all patients of both groups. |
| Comparison of the clinical outcomes of the scars in both groups. | There are a minimum of 154 and a maximum of 178 days between visit 3 and visit 5. | The clinical outcomes will be evaluated by VSS scoring at visit 3 (Day 14 +/- 2), visit 4 (Day 90 +/- 10) and visit 5 (Day 180 +/- 10). |
| The comparison of PROMs | There are a minimum of 154 and a maximum of 178 days between visit 3 and visit 5. | PROMs will be assessed in both groups by SCAR-Q scoring at Day 14 (+/- 2), Day 90 (+/- 10) and Day 180 (+/- 10). |
| The changes of different fibroblast subpopulations passing from unwounded skin to scarred, to repaired skin. | There are a maximum of 56 days + 90 +/- 10 days between the inital mole removal and visit 4. | Analysis of the initial FFPE skin samples compared to the analysis on Day 0 and Day 90 (+/- 10). |
Contacts
Primary ContactJöri Pünchera, M.D.
Backup ContactMichael Mühlstädt, M.D.
Outcome results
None listed