Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the efficacy and safety of ReCell grafting after CO2 laser abrasion with superficial full surface ablation, fractional laser treatment and conventional (deep) full surface CO2 laser ablation, to assess the practical aspects and the patient reported outcome and to assess the cellular composition of the graft.

Detailed Description
-----------------
Autologous epidermal cell suspension grafting is an effective method of surgical treatment in vitiligo, which is suitable for treating large areas with good cosmetic results. The ReCell Autologous Cell Harvesting Device (Avita Medical Europe Limited, Cambridge, UK) is a device which, compared to other forms of autologous epidermal cell suspension grafting, is easier in use showing similar results. With this device an epidermal cell suspension is created from a split skin graft, usually taken from the hip region. Currently, conventional ablative (full surface de-epidermisation) laser treatment in different laser settings is used as pre-treatment to prepare the acceptor site for transplantation. There is no evidence for the laser settings used and no studies are available on the use of a fractional laser as pre-treatment in autologous cell suspension grafting using ReCell (ReCell grafting). The investigators hypothesize that more superficial conventional ablative laser treatment and fractional ablative laser treatment are as effective as the current pre-treatment, whereas these treatments are less invasive, provide faster healing and prevent side effects like persisting erythema and scars. Furthermore, infiltration anaesthesia is not necessary with these less invasive treatments.

Official Title
-----------------
Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients: a Randomized Controlled Study on the Recipient Site Preparation

Conditions
-----------------
Segmental Vitiligo, Piebaldism

Intervention / Treatment
-----------------
* Device: ReCell
* Device: Full surface CO2 laser 200 mJ
* Device: Full surface CO2 laser 150 mJ
* Device: Fractional CO2 laser 7.5 mJ, 20%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with, segmental vitiligo or piebaldism under medical treatment at the Netherlands Institute for Pigment Disorders Age ≥18 Patient is willing and able to give written informed consent Segmental vitiligo stable since 12 months without systemic therapy or 12 months without topical therapy as defined by the absence of new lesions and/or enlargement of existing lesions. At least four depigmented lesions on the proximal extremities or trunk larger than 3x3 cm or one depigmented lesion on the proximal extremities or trunk of at least 12x3 cm. Exclusion Criteria: UV therapy or systemic immunosuppressive treatment during the last 12 months Local treatment of vitiligo during the last 12 months Vitiligo lesions with follicular or non-follicular repigmentations Skin type I Recurrent HSV skin infections Hypertrophic scars Keloid Cardiac insufficiency Patients with a history of hypersensitivity to (UVB or UVA) light and/or allergy to local anaesthesia. Patients who are pregnant or breast-feeding Patients not competent to understand what the procedures involves Patients with a personal history of melanoma or non-melanoma skin cancer Patients with atypical nevi. Known allergy to clarithromycin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Full surface CO2 laser 200mJ + ReCell<br>This test region will receive full surface pretreatment with the CO2 laser (Ultrapulse, ActiveFX handpiece, Lumenis Inc., Santa Clara, CA, USA) at 200 mJ (depth 209 µm) and density 3. After pretreatment ReCell autologous epidermal cell suspension will be applied on this test region. | Device: ReCell<br>* A split-thickness skin biopsy will be taken from the hip region of the patient. The skin biopsy that is obtained will be treated in the ReCell kit (Avita Medical Europe Ltd, Cambridge, UK): it will be placed in the heated enzyme solution, containing trypsin, in the device for 15-20 minutes to allow cell disaggregation. After that period, the biopsy will be taken from the enzyme solution and will be dipped in sodium lactate buffer solution. The biopsy will then be scraped to disaggregate the cells from the dermal epidermal junction. The epidermal cells are drawn up in a syringe. The prepared suspension will be dripped on both donor and acceptor site.<br>* Other names: ReCell autologous cell suspension grafting;Device: Full surface CO2 laser 200 mJ<br>* Full surface pretreatment with the CO2 laser (Ultrapulse, ActiveFX handpiece, Lumenis Inc., Santa Clara, CA, USA) at 200 mJ (depth 144 µm) and density 3<br>|
| Experimental: Full surface CO2 laser 150mJ + ReCell<br>This test region will receive full surface pretreatment with the CO2 laser (Ultrapulse, ActiveFX handpiece, Lumenis Inc., Santa Clara, CA, USA) at 150 mJ (depth 144 µm) and density 3. After pretreatment ReCell autologous epidermal cell suspension will be applied on this test region. | Device: ReCell<br>* A split-thickness skin biopsy will be taken from the hip region of the patient. The skin biopsy that is obtained will be treated in the ReCell kit (Avita Medical Europe Ltd, Cambridge, UK): it will be placed in the heated enzyme solution, containing trypsin, in the device for 15-20 minutes to allow cell disaggregation. After that period, the biopsy will be taken from the enzyme solution and will be dipped in sodium lactate buffer solution. The biopsy will then be scraped to disaggregate the cells from the dermal epidermal junction. The epidermal cells are drawn up in a syringe. The prepared suspension will be dripped on both donor and acceptor site.<br>* Other names: ReCell autologous cell suspension grafting;Device: Full surface CO2 laser 150 mJ<br>* Full surface pretreatment with the CO2 laser (Ultrapulse, ActiveFX handpiece, Lumenis Inc., Santa Clara, CA, USA) at 150 mJ (depth 144 µm) and density 3<br>|
| Experimental: Fractional CO2 laser 7.5mJ 20% + ReCell<br>This test region will receive pretreatment with the fractional CO2 laser (Ultrapulse, DeepFX handpiece, Lumenis Inc., Santa Clara, CA, USA) at 7.5 mJ/microbeam (depth 225 µm) and 20% density. After pretreatment ReCell autologous epidermal cell suspension will be applied on this test region. | Device: ReCell<br>* A split-thickness skin biopsy will be taken from the hip region of the patient. The skin biopsy that is obtained will be treated in the ReCell kit (Avita Medical Europe Ltd, Cambridge, UK): it will be placed in the heated enzyme solution, containing trypsin, in the device for 15-20 minutes to allow cell disaggregation. After that period, the biopsy will be taken from the enzyme solution and will be dipped in sodium lactate buffer solution. The biopsy will then be scraped to disaggregate the cells from the dermal epidermal junction. The epidermal cells are drawn up in a syringe. The prepared suspension will be dripped on both donor and acceptor site.<br>* Other names: ReCell autologous cell suspension grafting;Device: Fractional CO2 laser 7.5 mJ, 20%<br>* Pretreatment with the fractional CO2 laser (Ultrapulse, DeepFX handpiece, Lumenis Inc., Santa Clara, CA, USA) at 7.5 mJ/microbeam (depth 225 µm) and 20% density.<br>|
| No Intervention: Control<br>No intervention | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Repigmentation | Assessment will be done by sheets and a digital image analysis system. To assess the pigmentation, the contours of pigmentation are copied on a transparent sheet before and six months after treatment, after which the sheets are scanned using a predefined resolution. By comparing pre- and post-treatment pictures, the relative surface showing repigmentation expressed as percentage of the selected treated patch are computed. | 6 months after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PhGA | Blinded physician's assessment of repigmentation. Repigmentation will be classified as follows: 0-25%, 26-50%, 51-75%, 76-95%, 96-100% six months. | 6 months after intervention | 
| Side effects | Visual assessment of side effects per treatment region (erythema, hyperpigmentation, hypopigmentation and scar on a scale from 0-3) will be done by a blinded investigator six months. | 6 months after intervention | 
| Reepithelialization | One week after grafting reepithelialization will be assessed by a blinded physician and estimated on a 0 to 100% scale. | 1 week after intervention | 
| Colour difference | Colour difference i.e. the difference between normal pigmentation, erythema, and hyperpigmentation will be assessed with a DermaSpectrometer (Cortex Technology ApS, Hadsund, Denmark) | 6 months after intervention | 
| PGA | General outcome will be assessed by the patient per treatment region on a scale from 0-3 (Poor, Moderate, Good, and Excellent). | 6 months after intervention | 
| Pain | One week after grafting, pain will be assessed after grafting on a 100 mm visual analogue scale (VAS) per treatment region | 1 week after intervention | 
| Cell count | The superfluous of the suspension will be used for flow cytometric analyses of the cellular composition of the graft. | up to six hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ablative laser, Fractional laser, Vitiligo, Piebaldism, Cell suspension grafting