Evaluating the Efficacy of the Melanocyte Keratinocyte Transplantation Procedure in the Treatment of Vitiligo

Vitiligo is a dermatologic disease characterized by depigmentation of the skin. While the loss of melanocytes observed in vitiligo is driven by the immune system, repigmentation of the skin that occurs during UV light treatment is driven by melanocytes that migrate out of the hair follicle and into the epidermis or the activation of stem cells within the epidermis. Unfortunately, some skin areas affected by vitiligo have very few hair follicle melanocytes and an indeterminate number of epidermal melanocytes and therefore unable to respond to light therapy.

This pilot study seeks to examine the relative efficacy of different harvesting methods for the melanocyte keratinocyte transplant procedure (MKTP) in the treatment of vitiligo.

In addition, this study will analyze the tissue of excess tissue harvested during the procedure to identify distinct cellular and molecular features of chronic vitiligo.

Patients in Dr. Ganesan's clinic at the UCI (University of California, Irvine) Department of Dermatology will be approached for participation in the study. The study will include both men and women and will not be limited by race or ethnicity. The investigators will exclude individuals less than 18 years old for the study as the investigators believe it would be difficult for these subjects to tolerate the melanocyte keratinocyte transplant procedure. Participants will be offered a melanocyte keratinocyte transplant procedure with one of the three different tissue harvesting methods (a blade, suction blister) and the method without dissociation (Cellutome).

This study has three arms:

1. MKTP with Surgical Blade
2. MKTP with Negative Pressure Instrument (suction blistering device).
3. Suction blister grafting without cell dissociation utilizing Cellutome (a device used for treating chronic burn wounds)

Study Overview

• Status: Terminated
• Conditions: Vitiligo
• Intervention / Treatment: Procedure: MKTP with Surgical blade; Device: MKTP with Negative Pressure Instrument; Device: Suction blister grafting without cell dissociation

Detailed Description

In the first arm of the study, a normally pigmented area on the patient was anesthetized with 1% lidocaine with epinephrine. Using a surgical knife, the investigator removed a small portion of the epidermis that is unaffected by vitiligo from a small area (2cm2) on the patient's thigh to obtain donor cells. Epidermis that was harvested with the surgical knife was washed with Lactated Ringer's solution three times and then dissociated using trypsin to separate the cells into a single cell suspension. The recipient area to be grafted was ablated with an Erbium YAG(yttrium aluminum garnet)laser. Half of the dissociated single cells from the donor area (thigh)was then transplanted on to the area affected by vitiligo that the participant is interested in grafting (5 cm2 area).

The investigator then evaluated response to treatment in the transplanted areas at 1 day, 1 week, 1 month and 3 months, and 6 months by both photography and quantifying the VASI(Vitiligo Area Scoring Index) score.

VASI(Vitiligo Area Scoring Index)is the percentage of vitiligo involvement and is calculated in terms of hand units. One hand unit is approximately equivalent to 1% of the total body surface area.

In the second arm of the study, the investigator used a minimally invasive procedure (suction blister grafting) to sample the grafted skin and donor skin- this method can separate the epidermis from the dermis without inducing a scar. A normally pigmented area on the upper thigh was anesthetized with 1% lidocaine with epinephrine. Using a suction blister technique, the investigator removed a small portion of the epidermis that was unaffected by vitiligo from a small area (4 cm2 or 0.6 inch cm2) on the patient's thigh to obtain donor cells. Epidermis that was harvested was washed with Lactated Ringer's solution three times and then dissociated using trypsin to separate the cells into a single cell suspension. The recipient areas to be grafted were used to harvest epidermis using a suction blister device. Half of the dissociated single cells from the donor area (thigh) were then transplanted on to the area affected by vitiligo that the patient was interested in grafting (5 cm2 area or 0.7 inch2). The suction blister skin from the recipient sites was simultaneously dissociated into a single cell suspension. A portion of the remainder of the cells (from both the donor and recipient site) was subjected to flow sorting to quantify the populations of melanocytes and keratinocytes and to detailed molecular analysis (single-cell RNA sequencing and histology) to characterize the molecular features of chronic vitiligo. The investigator then evaluated response to treatment in the transplanted areas at 1 day, 1 week, 1 month and 3 months, and 6 months by both photography and quantifying the VASI score. This arm of the study is complete.

In the third arm of the study, the investigator uses a minimally invasive procedure (suction blister grafting without cell dissociation) to sample the grafted skin and donor skin- this method can separate the epidermis from the dermis without inducing a scar. A normally pigmented area on the upper thigh will be anesthetized with 1% lidocaine with epinephrine. Using an epidermal harvesting system which is a suction blister technique, the investigator will remove multiple small portions (about 128 blisters-1.8 mm in diameter) of the epidermis unaffected by vitiligo from a small normal area (5 cm2 ) on the patient's thigh to obtain donor cells and using a regular negative pressure instrument for removing four samples for histopathological study (two from the vitiligo area and two from the normal donor skin). The epidermis from the donor area (thigh) will then be transplanted on to the area affected by vitiligo that the patient is interested in grafting. Also, the four portions from the normal skin and the recipient site will be sent for the histopathological evaluation.

The investigator will then evaluate response to treatment in the transplanted areas at 1 day, 1 week, 1 month and 3 months, and 6 months by both photography, quantifying the change in depigmented surface area, and the VASI(Vitiligo Area Scoring Index) score. Also, the investigator will evaluate the two vitiligo samples and two normal skin samples through histopathology to assess where the unique populations of cells identified in their RNA-sequencing analysis are localized (obtained from arm 2). The investigator hypothesizes that his transplant procedure will yield excellent to good repigmentation, resulting in a mean of 60% reduction in surface area (SD=30%) from baseline to 6-month follow up. With a sample size of 5 patients, this study will achieve 90% power to test this hypothesis based on a two-sided paired t-test at p=0.05 significance level. In addition, the investigator will compare the results from the 7 patients harvested using the surgical blade technique (procedure already completed and follow up results pending) with the results from 7 patients harvested with the suction blisters (completed) and seven patients from the newly proposed experimental group (three completed to date).

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anand K Ganesan, MD, PhD; Phone Number: (949) 824-2926; Email: aganesan@hs.uci.edu
• Study Contact Backup: Name: Pezhman Mobasher, MD; Phone Number: (949) 824-0547; Email: pmobashe@hs.uci.edu

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Verified diagnosis of vitiligo by a board-certified dermatologist
• Candidate for vitiligo treatment as determined by lead researcher
• Has a 5 cm2 area of vitiligo and an area on the upper thigh that is not affected by the disease
• Over 18 years of age at the time of signing the informed consent form
• Ability to understand, abide by and participate in study procedures

Exclusion Criteria:

• Inability to understand or abide by instructions for participation in study and procedure
• Pregnant or lactating women
• Less than 18 years old at the time of signing the informed consent form
• Current use of tobacco products or within 1 month prior to procedure date
• History of coagulation disorder, platelet dysfunction disorder, platelet count less than <150,000 platelets per microliter
• History of poor wound healing or condition that would compromise optimal healing of graft site as deemed by lead researcher
• History of keloids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MKTP with Surgical Blade; The investigator harvested skin from the donor site and skin from the recipient site using a surgical blade in the first arm of the study.	Procedure: MKTP with Surgical blade; In this procedure, the donor skin will be harvested with a surgical blade and the donor skin will be dissociated
Experimental: MKTP with Negative Pressure Instrument; Blister grafting technique with dissociation of the cells was performed in the second arm of the study.	Device: MKTP with Negative Pressure Instrument; In this procedure, the investigator uses a negative pressure instrument to create a few blisters on the donor skin and use the blisters for grafting after cell dissociation.
Experimental: Suction blister grafting without cell dissociation; In this arm, transplanting the blisters without dissociation of the cells will be conducted.	Device: Suction blister grafting without cell dissociation; In this procedure, an automated suction blister device will be used to create micro domes and these micro domes will be used directly for grafting without dissociation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of change in the transplanted areas	Percentage of change in the transplanted areas will be evaluated by photography	6 months
Percentage of change in the transplanted areas in the transplanted areas	Percentage of change in the transplanted areas will be evaluated by VASI (Vitiligo Area Scoring Index). The minimum value is 0 and maximum value is 100. and higher scores mean worse outcome.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of healing	The investigator will evaluate how long it took the patient to heal at both the donor and graft site	6 months
Rate of Complication	The investigator will record the rate of complications of the procedure itself.	6 months

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Investigators: Principal Investigator: Anand K Ganesan, MD, PhD, University of California, Irvine

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2017
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: May 1, 2020
• First Posted (Actual): May 5, 2020

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 15, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Transplantation; Vitiligo; Procedure; Melanocyte; Keratinocyte
• Additional Relevant MeSH Terms: Skin Diseases; Pigmentation Disorders; Hypopigmentation; Vitiligo
• Other Study ID Numbers: HS#: 2017-3518

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes