Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients

Piebaldism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02458417
• Other study ID #: NL49720.018.14
• Status: Completed
• Phase: Phase 4
• First received: May 26, 2015
• Last updated: March 31, 2017
• Start date: May 2015
• Est. completion date: January 2016

Study information

• Verified date: May 2015
• Source: Netherlands Institute for Pigment Disorders
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Piebaldism
• Segmental Vitiligo
• Vitiligo

Intervention

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.
• 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
• 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
• 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.

Locations

Country	Name	City	State
Netherlands	Netherlands Institute for Pigment disorders	Amsterdam

Sponsors (2)

Lead Sponsor	Collaborator
Netherlands Institute for Pigment Disorders	Avita Medical

Country where clinical trial is conducted

Netherlands, 

References & Publications (33)

Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011 Sep;65(3):473-91. doi: 10.1016/j.jaad.2010.11.061. Review. — View Citation

Boersma BR, Westerhof W, Bos JD. Repigmentation in vitiligo vulgaris by autologous minigrafting: results in nineteen patients. J Am Acad Dermatol. 1995 Dec;33(6):990-5. — View Citation

Brightman LA, Brauer JA, Anolik R, Weiss E, Karen J, Chapas A, Hale E, Bernstein L, Geronemus RG. Ablative and fractional ablative lasers. Dermatol Clin. 2009 Oct;27(4):479-89, vi-vii. doi: 10.1016/j.det.2009.08.009. Review. — View Citation

Cervelli V, De Angelis B, Balzani A, Colicchia G, Spallone D, Grimaldi M. Treatment of stable vitiligo by ReCell system. Acta Dermatovenerol Croat. 2009;17(4):273-8. — View Citation

Cervelli V, Spallone D, Lucarini L, Palla L, Brinci L, De Angelis B. Treatment of stable vitiligo hands by ReCell system: a preliminary report. Eur Rev Med Pharmacol Sci. 2010 Aug;14(8):691-4. — View Citation

Chernoff G, Slatkine M, Zair E, Mead D. SilkTouch: a new technology for skin resurfacing in aesthetic surgery. J Clin Laser Med Surg. 1995 Apr;13(2):97-100. — View Citation

Drake LA, Dinehart SM, Farmer ER, Goltz RW, Graham GF, Hordinsky MK, Lewis CW, Pariser DM, Skouge JW, Turner ML, Webster SB, Whitaker DC, Lowery BJ, Nordlund JJ, Grimes PE, Halder RM, Minus HR. Guidelines of care for vitiligo. American Academy of Dermatology. J Am Acad Dermatol. 1996 Oct;35(4):620-6. — View Citation

Falabella R. Grafting and transplantation of melanocytes for repigmenting vitiligo and other types of leukoderma. Int J Dermatol. 1989 Jul-Aug;28(6):363-9. Review. — View Citation

Fongers A, Wolkerstorfer A, Nieuweboer-Krobotova L, Krawczyk P, Tóth GG, van der Veen JP. Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo: effect of disease activity. Br J Dermatol. 2009 Nov;161(5):1105-11. doi: 10.1111/j.1365-2133.2009.09367.x. — View Citation

Gauthier Y, Surleve-Bazeille JE. Autologous grafting with noncultured melanocytes: a simplified method for treatment of depigmented lesions. J Am Acad Dermatol. 1992 Feb;26(2 Pt 1):191-4. — View Citation

Gawkrodger DJ, Ormerod AD, Shaw L, Mauri-Sole I, Whitton ME, Watts MJ, Anstey AV, Ingham J, Young K. Vitiligo: concise evidence based guidelines on diagnosis and management. Postgrad Med J. 2010 Aug;86(1018):466-71. doi: 10.1136/pgmj.2009.093278. Review. — View Citation

Gawkrodger DJ, Ormerod AD, Shaw L, Mauri-Sole I, Whitton ME, Watts MJ, Anstey AV, Ingham J, Young K; Therapy Guidelines and Audit Subcommittee, British Association of Dermatologists.; Clinical Standards Department, Royal College of Physicians of London.; Cochrane Skin Group.; Vitiligo Society.. Guideline for the diagnosis and management of vitiligo. Br J Dermatol. 2008 Nov;159(5):1051-76. doi: 10.1111/j.1365-2133.2008.08881.x. — View Citation

Gravante G, Di Fede MC, Araco A, Grimaldi M, De Angelis B, Arpino A, Cervelli V, Montone A. A randomized trial comparing ReCell system of epidermal cells delivery versus classic skin grafts for the treatment of deep partial thickness burns. Burns. 2007 Dec;33(8):966-72. — View Citation

Hann SK, Lee HJ. Segmental vitiligo: clinical findings in 208 patients. J Am Acad Dermatol. 1996 Nov;35(5 Pt 1):671-4. — View Citation

Hantash BM, Bedi VP, Chan KF, Zachary CB. Ex vivo histological characterization of a novel ablative fractional resurfacing device. Lasers Surg Med. 2007 Feb;39(2):87-95. — View Citation

Hunzeker CM, Weiss ET, Geronemus RG. Fractionated CO2 laser resurfacing: our experience with more than 2000 treatments. Aesthet Surg J. 2009 Jul-Aug;29(4):317-22. doi: 10.1016/j.asj.2009.05.004. Review. — View Citation

Linthorst Homan MW, Spuls PI, de Korte J, Bos JD, Sprangers MA, van der Veen JP. The burden of vitiligo: patient characteristics associated with quality of life. J Am Acad Dermatol. 2009 Sep;61(3):411-20. doi: 10.1016/j.jaad.2009.03.022. Epub 2009 Jul 3. — View Citation

Linthorst Homan MW, Wolkerstorfer A, Sprangers MA, van der Veen JP. Digital image analysis vs. clinical assessment to evaluate repigmentation after punch grafting in vitiligo. J Eur Acad Dermatol Venereol. 2013 Feb;27(2):e235-8. doi: 10.1111/j.1468-3083.2012.04568.x. — View Citation

Malakar S, Dhar S. Treatment of stable and recalcitrant vitiligo by autologous miniature punch grafting: a prospective study of 1,000 patients. Dermatology. 1999;198(2):133-9. — View Citation

Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR. Fractional photothermolysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med. 2004;34(5):426-38. — View Citation

Mulekar SV, Ghwish B, Al Issa A, Al Eisa A. Treatment of vitiligo lesions by ReCell vs. conventional melanocyte-keratinocyte transplantation: a pilot study. Br J Dermatol. 2008 Jan;158(1):45-9. — View Citation

Mulekar SV. Long-term follow-up study of segmental and focal vitiligo treated by autologous, noncultured melanocyte-keratinocyte cell transplantation. Arch Dermatol. 2004 Oct;140(10):1211-5. — View Citation

Murakami T, Fukai K, Oiso N, Hosomi N, Kato A, Garganta C, Barnicoat A, Poppelaars F, Aquaron R, Paller AS, Ishii M. New KIT mutations in patients with piebaldism. J Dermatol Sci. 2004 Jun;35(1):29-33. — View Citation

Navarro FA, Stoner ML, Lee HB, Park CS, Wood FM, Orgill DP. Melanocyte repopulation in full-thickness wounds using a cell spray apparatus. J Burn Care Rehabil. 2001 Jan-Feb;22(1):41-6. — View Citation

Njoo MD, Westerhof W. Vitiligo. Pathogenesis and treatment. Am J Clin Dermatol. 2001;2(3):167-81. Review. — View Citation

Olsson MJ, Juhlin L. Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension. Br J Dermatol. 2002 Nov;147(5):893-904. — View Citation

Ongenae K, Van Geel N, De Schepper S, Naeyaert JM. Effect of vitiligo on self-reported health-related quality of life. Br J Dermatol. 2005 Jun;152(6):1165-72. — View Citation

Ragland HP, McBurney E. Complications of resurfacing. Semin Cutan Med Surg. 1996 Sep;15(3):200-7. Review. — View Citation

Taïeb A, Picardo M. Clinical practice. Vitiligo. N Engl J Med. 2009 Jan 8;360(2):160-9. doi: 10.1056/NEJMcp0804388. Review. — View Citation

van Geel N, Ongenae K, Naeyaert JM. Surgical techniques for vitiligo: a review. Dermatology. 2001;202(2):162-6. Review. — View Citation

van Geel N, Wallaeys E, Goh BK, De Mil M, Lambert J. Long-term results of noncultured epidermal cellular grafting in vitiligo, halo naevi, piebaldism and naevus depigmentosus. Br J Dermatol. 2010 Dec;163(6):1186-93. doi: 10.1111/j.1365-2133.2010.10014.x. — View Citation

Wind BS, Meesters AA, Kroon MW, Beek JF, van der Veen JP, Nieuweboer-Krobotová L, Bos JD, Wolkerstorfer A. Punchgraft testing in vitiligo; effects of UVA, NB-UVB and 632.8 nm Helium-Neon laser on the outcome. J Eur Acad Dermatol Venereol. 2011 Oct;25(10):1236-7. doi: 10.1111/j.1468-3083.2010.03874.x. — View Citation

Wood FM, Giles N, Stevenson A, Rea S, Fear M. Characterisation of the cell suspension harvested from the dermal epidermal junction using a ReCell® kit. Burns. 2012 Feb;38(1):44-51. doi: 10.1016/j.burns.2011.03.001. — View Citation

* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Skin type	Fitzpatrick skin type	week 0
Other	VIDA score	Classification of disease activity according to VIDA scale	week 0
Other	Duration of disease	Duration of disease	week 0
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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