Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Piebaldism; Segmental Vitiligo
• 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%

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Netherlands Institute for Pigment Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; No intervention
Active Comparator: Full surface CO2 laser 200mJ + ReCell; 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; 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.; Other Names: ReCell autologous cell suspension grafting; Device: Full surface CO2 laser 200 mJ; 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
Experimental: Full surface CO2 laser 150mJ + ReCell; 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; 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.; Other Names: ReCell autologous cell suspension grafting; Device: Full surface CO2 laser 150 mJ; 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
Experimental: Fractional CO2 laser 7.5mJ 20% + ReCell; 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; 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.; Other Names: ReCell autologous cell suspension grafting; Device: Fractional CO2 laser 7.5 mJ, 20%; 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.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin type	Fitzpatrick skin type	week 0
VIDA score	Classification of disease activity according to VIDA scale	week 0
Duration of disease	Duration of disease	week 0

Collaborators and Investigators

• Sponsor: Netherlands Institute for Pigment Disorders
• Collaborators: Avita Medical
• Investigators: Principal Investigator: Albert Wolkerstorfer, MD, PhD, Netherlands Institute for Pigment Disorders, Department of Dermatology, Academic Medical Center, University of Amsterdam; Study Director: Menno A. De Rie, MD, PhD, Department of Dermatology, Academic Medical Center, University of Amsterdam

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: May 26, 2015
• First Submitted That Met QC Criteria: May 27, 2015
• First Posted (Estimate): June 1, 2015

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Fractional laser; Vitiligo; Ablative laser; Piebaldism; Cell suspension grafting
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Eye Diseases, Hereditary; Metabolism, Inborn Errors; Amino Acid Metabolism, Inborn Errors; Pigmentation Disorders; Hypopigmentation; Albinism; Vitiligo; Piebaldism
• Other Study ID Numbers: NL49720.018.14