Effect of YAP1-inhibition in Surgical Wounds.
ConditionScar Formation
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-55
SponsorJöri Pünchera
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
NaCl (placebo)
DrugDuring the safety margin excision, the placebo (NaCl) will be injected into the wound before suturing.
Verteporfin Injection
DrugDuring the safety margin excision, the study drug (Verteporfin) will be injected into the wound before suturing.
Treatment groups
24 Participants
are divided into 2 treatment groupsGroup A: Study arm (verteporfin)Experimental treatment 1 intervention
Group B: Placebo armPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Quantification of the profibrotic mesenchymal fibroblast subpopulation in the study group compared to the placebo group.
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.
Time frame
There are 90 +/- 10 days between visit 1 and visit 4.Secondary outcomes
1
The changes of fibroblast subpopulations, clusters, and their different cell-cell interactions in both groups before and after the study intervention.
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.
Time frame
There are 90 +/- 10 days between visit 1 and visit 4.2
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
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.
Time frame
There are 90 +/- 10 days between visit 1 and visit 4.3
Quantification of the different fibroblast subpopulations in unwounded, healthy skin.
In all patients, 2 slices of the initial FFPE skin samples will be analyzed.
Time frame
The initial excision will take place 21 to 54 days before V1.4
The changes of different fibroblast subpopulations passing from unwounded skin to scarred, to repaired skin.
Analysis of the initial FFPE skin samples compared to the analysis on Day 0 and Day 90 (+/- 10).
Time frame
There are a maximum of 56 days + 90 +/- 10 days between the inital mole removal and visit 4.Locations
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Jöri Pünchera
Lead sponsor
University Hospital, Geneva
Sponsor institution
University of Geneva, Switzerland
Collaborator
University Hospital, Geneva
Collaborator
Source ClinicalTrials.gov
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