<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03013049</url>
  </required_header>
  <id_info>
    <org_study_id>INT/IEC/2016/2675</org_study_id>
    <nct_id>NCT03013049</nct_id>
  </id_info>
  <brief_title>A Novel Surgical Method in the Treatment of Unstable Vitiligo</brief_title>
  <official_title>A Comparative Study Between Autologous Non Cultured Epidermal Cell Suspension Versus Combination of Autologous Non Cultured Epidermal Cell Suspension and Non Cultured Dermal Cell Suspension in Stable Vitiligo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Postgraduate Institute of Medical Education and Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Postgraduate Institute of Medical Education and Research</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vitiligo is a complex disease causing a selective, often progressive, loss of functioning&#xD;
      melanocytes from epidermal basal layer resulting in white patches on the skin and&#xD;
      occasionally mucosae. Worldwide prevalence of vitiligo is around 1% whereas in India it is&#xD;
      around 3-4% ranging from 0.46% to 8.8%.&#xD;
&#xD;
      Etiopathogenesis of vitiligo is multifactorial consisting of genetic, immunological and&#xD;
      environmental factors. Environmental and genetic factors act in concert to destroy&#xD;
      melanocytes. Reactive oxygen species (ROS) play important roles in vitiligo pathology,but the&#xD;
      autoimmune pathogenesis has been proposed as one of the main causes of vitiligo.&#xD;
&#xD;
      Surgical methods, mainly transplantation of non cultured epidermal cell suspension are&#xD;
      effective treatment for stable vitiligo. Transplantation of autologous noncultured epidermal&#xD;
      cell suspension and non-cultured dermal cell suspension in combination (a mode of cellular&#xD;
      grafting technique) is a novel surgical method for the treatment of vitiligo. Cytotoxic CD8+&#xD;
      ( cluster of differentiation 8+) cells in vitiligo perilesions may dictate the fate of&#xD;
      transplantation, and strategies against CD8+ T cell activation might be beneficial for&#xD;
      patients undergoing melanocyte transplantation. Mesenchymal cells could inhibit T cell&#xD;
      proliferation and induce T cell apoptosis. Bartsch first identified and characterized dermal&#xD;
      mesenchymal cells (DMCs). They have a multi-lineage differentiation potential into&#xD;
      adipocytes, osteocytes and chondrocytes.Vitiligo patients' autologous melanocytes&#xD;
      transplantation efficiency may be predicted by perilesional skin-homing CD8+ T cell&#xD;
      activities, and the immunoregulatory DMCs might be used as auxiliary agent to improve the&#xD;
      efficacy.&#xD;
&#xD;
      This pilot study is planned to compare transplantation of autologous noncultured epidermal&#xD;
      cell suspension v/s its combination with non-cultured dermal cell suspension as a novel&#xD;
      method in vitiligo surgery in stability of vitiligo with regards to extent of repigmentation,&#xD;
      color matching of repigmented area, patient satisfaction and adverse events if any. This is&#xD;
      the first study using transplantation of autologous noncultured epidermal cell suspension and&#xD;
      non-cultured dermal cell suspension in combination as a new modality in vitiligo surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitiligo, the most common depigmenting disorder is an 'idiopathic', acquired pigmentary&#xD;
      disorder caused by the loss of functional melanocytes from the epidermis. The course of the&#xD;
      disease is unpredictable but is often progressive with phases of stabilized depigmentation.&#xD;
      It usually begins during childhood or young adulthood. Approximately one third to one half of&#xD;
      the patients develops the disease before the age of 20 years. The presence of vitiligo on&#xD;
      exposed areas of body leads to social embarrassment, psychological turmoil, and cosmetic&#xD;
      disfigurement in those affected.&#xD;
&#xD;
      Its prevalence is 1%, ranging from 0.1 to &gt; 8.8% in different countries of the globe. Both&#xD;
      sexes are equally affected although the greater number of reports among females is probably&#xD;
      due to the greater social consequences to women and girls affected by this condition.&#xD;
&#xD;
      Treatment options A number of therapeutic options for vitiligo are available but there is&#xD;
      still a need for a treatment that is promptly effective. There is no curative treatment for&#xD;
      this condition. Management of vitiligo is a real challenge for a dermatologist.&#xD;
&#xD;
      Medical therapies:&#xD;
&#xD;
      Corticosteroids (Topical, intralesional and systemic), Oral mini pulse, PUVA (topical and&#xD;
      systemic), NBUVB, calcipotriol and tacrolimus are used most widely. Some of the less commonly&#xD;
      used medical modalities include phenylalanine, khellin, topical minoxidil, levamisole and&#xD;
      melagenina. Recently oral minocycline was shown to be effective in treating vitiligo.&#xD;
&#xD;
      Most of these therapies aim to restore melanocyte function by their anti-inflammatory or&#xD;
      immunomodulatory action and by preventing melanocyte auto destruction so that normal skin&#xD;
      appearance and function is restored.&#xD;
&#xD;
      Surgical therapies:&#xD;
&#xD;
      All patients with vitiligo should be initially treated with medical methods. Surgical methods&#xD;
      are important solutions for stable vitiligo refractory to medical treatment. High&#xD;
      repigmentation rates are obtained with all procedures so far described in most anatomic&#xD;
      locations, but they are of little help for acral areas and bony prominences. Unilateral&#xD;
      vitiligo is the clinical form with the best response to grafting and transplant methods, and&#xD;
      a good proportion of patients with stable bilateral disease also respond adequately.&#xD;
      Nevertheless, appropriate patient selection is important to achieve maximal results.However&#xD;
      none of the surgical modalities developed so far is uniformly effective in all patients and&#xD;
      body sites and there is need for constant research and innovations for better surgical&#xD;
      therapeutic options for vitiligo.&#xD;
&#xD;
      Aims of various surgical procedures:&#xD;
&#xD;
      A) Camouflage Tattooing: Introduction of artificial pigments into the lesions for permanent&#xD;
      camouflage.&#xD;
&#xD;
      B) Excision: Removal of the depigmented areas, e.g. excision with primary closure and&#xD;
      covering with thin Thiersch's graft.&#xD;
&#xD;
      C) Melanocyte transplantation: commonly used methods of autologous transplant of melanocytes&#xD;
      are&#xD;
&#xD;
      Tissue grafts:&#xD;
&#xD;
        1. Thin and ultra-thin split thickness grafts (STSG)&#xD;
&#xD;
        2. Suction blister epidermal grafts(SBEG)&#xD;
&#xD;
        3. Mini punch grafts (MPG)&#xD;
&#xD;
        4. Hair follicular grafts (HFG)&#xD;
&#xD;
           Cellular grafts:&#xD;
&#xD;
        5. Noncultured epidermal cell suspension (NCES)&#xD;
&#xD;
        6. Cultured &quot;pure&quot; melanocytes (CM)&#xD;
&#xD;
        7. Cultured epithelial grafts (CE)&#xD;
&#xD;
        8. Autologous noncultured extracted hair follicle outer root sheath cell suspension also&#xD;
           called follicular cell suspension (FCS) D) Therapeutically wounding the lesion to&#xD;
           stimulate the melanocytes from the periphery and the black hair follicles to&#xD;
           proliferate, migrate and re-pigment the lesion, e.g. therapeutic dermabrasion, laser&#xD;
           ablation, cryosurgery (liquid nitrogen spraying), needling and local application of&#xD;
           phenol or trichloroacetic acid.&#xD;
&#xD;
      Every method has its own advantages and disadvantages. As there are no specific data&#xD;
      available from the prospective studies in this field, it is not easy to recommend which&#xD;
      surgical approach to vitiligo offers the best result.&#xD;
&#xD;
      'Vitiligo global issues consensus conference, 2011' convened by Vitiligo European Task Force&#xD;
      (VETF), concluded that assessment of 'overall' stability is inaccurate and unreliable,&#xD;
      whereas individual lesion stability is more reliable, especially when used in the context of&#xD;
      surgical intervention.&#xD;
&#xD;
      Methods and Size of Lesions:&#xD;
&#xD;
      Depending on the size of the treated area, the method may vary. Simple methods such as mini&#xD;
      punch grafting and suction epidermal grafting are useful for small or medium sized lesions.&#xD;
      On the contrary, for extensive depigmented defects, cellular transplants may be required.&#xD;
&#xD;
      Age:&#xD;
&#xD;
      Because of the invasive nature of surgical procedures, they are not recommended in children;&#xD;
      nevertheless, highly motivated adolescents can be treated under sedation or general&#xD;
      anesthesia. Also, it is not surprising to see patients beyond the age of 50 years who may be&#xD;
      interested in surgical repigmentation.&#xD;
&#xD;
      Psychological Aspects:&#xD;
&#xD;
      Some patients with high emotional trauma because of depigmentation may seek advice for&#xD;
      invasive procedures. However, a psychological evaluation may be needed to ascertain the real&#xD;
      need for surgical treatment.&#xD;
&#xD;
      Photographic Record:&#xD;
&#xD;
      Illustrations are recommended to help in determining the percentage of improvement, quality&#xD;
      of repigmentation and possible side effects.&#xD;
&#xD;
      Patient's Expectations:&#xD;
&#xD;
      Repigmentation is not always comparable with normally pigmented skin and the final results&#xD;
      vary considerably from patient to patient. However, most individuals are pleased with the&#xD;
      achieved results; minor imperfections are far less important than the noticeable&#xD;
      repigmentation of vitiliginous skin, mainly in ethnic skin patients with a dark complexion;&#xD;
      sometimes surgical repigmentation may look even better than what is observed in many patients&#xD;
      after medical therapy.&#xD;
&#xD;
      Method and Donor Site:&#xD;
&#xD;
      Appropriate training with a specific method is an important prerequisite for surgical&#xD;
      therapy. Donor site should be as hidden as possible and the gluteal region may be suitable&#xD;
      for this purpose in most patients.&#xD;
&#xD;
      Success rates of different surgical options:&#xD;
&#xD;
      Among all procedures, suction blister epidermal grafts and thin and ultra-thin&#xD;
      split-thickness grafts seem to be the most effective procedures, with overall success rates&#xD;
      of 80.3% (CI 76.4-84.2%) and 77.9% (CI 72.2-83.6%) respectively. But, a recent randomized&#xD;
      study directly comparing NCES and SBEG showed NCES is significantly better than SBEG. Among&#xD;
      cellular grafts, all techniques seem to be equally effective with success rates of 61.1% (CI&#xD;
      56.1-66.1%), 63.6% (CI 57.2-70%), and 63.6% (CI 55.8-70.6%) for noncultured epidermal cell&#xD;
      suspension, cultured melanocytes and cultured epidermis respectively. The mean repigmentation&#xD;
      with noncultured extracted outer root sheath cell suspension is about 65.7%).&#xD;
&#xD;
      NONCULTURED EPIDERMAL CELL SUSPENSION The technique of noncultured epidermal suspension was&#xD;
      pioneered by Gauthier et al. The suspension was prepared by incubating the donor skin&#xD;
      obtained from the scalp in trypsin 0.25% for 18 hrs. The suspension was injected into&#xD;
      blisters raised by cryotherapy. Eight out of the 12 patients treated had &gt; 70% repigmentation&#xD;
      at the vitiligo site. It was proposed that the presence of keratinocytes in the suspension&#xD;
      supplies essential growth factors for melanocyte growth. They stated that this technique&#xD;
      could emerge as simple and effective alternative to the costly cultured melanocyte&#xD;
      transplantation technique.&#xD;
&#xD;
      NON-CULTURED DERMAL CELL SUSPENSION&#xD;
&#xD;
      Dermal mesenchymal cells were originally isolated from the dermis of juvenile and adult mice&#xD;
      by Toma et al., afterwards, same group identified such a cell population in human skin. Georg&#xD;
      Bartsch firstly identified and characterized dermal mesenchymal cells (DMCs). DMCs had&#xD;
      multi-lineage differentiation potential into adipocytes, osteocytes and chondrocytes. The&#xD;
      surface antigenic profile of DMCs was positive for CD90 but differs in regard to negativity&#xD;
      for CD34.&#xD;
&#xD;
      Zhou et al investigated the factors determining the efficiency of autologous melanocyte&#xD;
      transplantation of vitiligo patients by focusing on perilesional skin homing CD8+ T&#xD;
      lymphocytes, and studied the potential effects of dermal mesenchymal cells (DMCs) on CD8+ T&#xD;
      cell activities in vitro. The patients with high number of perilesional CD8+ T cells were&#xD;
      associated with poor repigmentation rate and a significant lesser number of CD8+ T cells was&#xD;
      infiltrating in patients with excellent or good re-pigmentation responses. Also, skin homing&#xD;
      CD8+ T cells proliferation was significantly inhibited when co-culture with DMCs at 1:1 ratio&#xD;
      as the percentage of proliferative CD8+ T cells dropped from 94.72% to 39.50% (p,0.05) after&#xD;
      DMCs co-culture. In the co-culture system, DMCs significantly inhibited skin homing CD8+ T&#xD;
      proliferation and induced those cells apoptosis. These data confirm that DMCs induces&#xD;
      significant immunosuppressive abilities against skin homing CD8+ T lymphocytes and may help&#xD;
      improve the efficacy of melanocytes transplantation. Non-cultured Dermal Cell Suspension&#xD;
      (NDCS) is a novel method to increase the efficacy of non-cultured epidermal cell suspension&#xD;
      (NCES).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2016</start_date>
  <completion_date type="Anticipated">June 2017</completion_date>
  <primary_completion_date type="Anticipated">June 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>extent of repigmentation</measure>
    <time_frame>6 months</time_frame>
    <description>Repigmentation will be assessed as follows -&#xD;
≤25% Minimal repigmentation 26-50% Mild repigmentation 51-75% Moderate repigmentation 76-90% Marked repigmentation &gt;90% Excellent repigmentation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pattern of repigmentation</measure>
    <time_frame>6 months</time_frame>
    <description>diffuse peri follicular migrating from the borders</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Vitiligo</condition>
  <arm_group>
    <arm_group_label>Non cultured epidermal cell suspension</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In 20 patients who have stable vitiligo with the duration of stability more than 3 months, non cultured epidermal cell suspension will be done. Patients will be divided into 2 subgroups of 10 patients each of stability duration of 3-6 months and more than 1 year respectively and non cultured epidermal cell suspension will be done.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non cultured dermal cell suspension</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In 20 patients who have stable vitiligo with the duration of stability more than 3 months, combination of non cultured epidermal cell suspension and non cultured dermal cell suspension will be done. Patients will be divided into 2 subgroups of 10 patients each of stability duration of 3-6 months and more than 1 year respectively and combination of non cultured epidermal cell suspension and non cultured dermal cell suspension will be done.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Non cultured epidermal cell suspension</intervention_name>
    <description>Non cultured epidermal cell suspension Split thickness skin specimen will be transferred under aseptic conditions to a container with normal salineand transferred to laboratory. There, the skin graft will be transferred to Trypsin-EDTA solution (0.25% trypsin and 0.02% EDTA) in a Petri dish and incubated overnight at 4°C in 5% CO2 to separate the epidermis from the dermis.Afterwards, the Trypsin-EDTA solution will be removed and PBS will be added and pipetted well so as to separate the cells from the tissue.The suspension will be centrifuged at 1000 rpm for 5 minutes.The supernatant will then be discarded and Phosphate buffer saline is added to make suspension of non-cultured epidermal cells.</description>
    <arm_group_label>Non cultured dermal cell suspension</arm_group_label>
    <arm_group_label>Non cultured epidermal cell suspension</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Non cultured dermal cell suspension</intervention_name>
    <description>Non-cultured Dermal Cell Suspension Skin punch will be collected in phosphate buffer saline (PBS) with antibiotics (penicillin and streptomycin). The epidermis will be cut off from dermis carefully using a surgical blade (Epidermal part will be used for the epidermal cell suspension). Dermis will be then cut into small pieces and incubated in collagenase (1mg/ml) overnight at room temperature. Next day content will be diluted with PBS and centrifuged at 1000rpm for 5 minutes. Pellet will be washed three times with PBS to remove collagenase activity. Phosphate buffer saline is added to make suspension of non-cultured dermal cells and will be used for the autologous transplantation.</description>
    <arm_group_label>Non cultured dermal cell suspension</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with clinical diagnosis of focal, segmental or generalized vitiligo which has&#xD;
             been stable for more than 3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age less than 18 years&#xD;
&#xD;
          2. Pregnancy&#xD;
&#xD;
          3. Patient with actively spreading vitiligo&#xD;
&#xD;
          4. Appearance of new lesions&#xD;
&#xD;
          5. History of Koebnerisation&#xD;
&#xD;
          6. History of hypertrophic scars or keloidal tendency&#xD;
&#xD;
          7. Bleeding disorders&#xD;
&#xD;
          8. Patients with unrealistic expectation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Davinder Parsad, MD</last_name>
    <phone>9736060361</phone>
    <phone_ext>+91</phone_ext>
    <email>parsad@me.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>PGIMER</name>
      <address>
        <city>Chandigarh</city>
        <zip>160012</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Davinder Parsad, MD</last_name>
      <phone>9876060361</phone>
      <email>parsad@me.com</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>December 27, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>January 5, 2017</last_update_submitted>
  <last_update_submitted_qc>January 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
    <investigator_full_name>Davinder Parsad</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitiligo</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>February 21, 2018</submitted>
    <returned>October 5, 2018</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03013049
org study id: INT/IEC/2016/2675
nct id: NCT03013049
lead sponsor: 
has dmc: Yes
Vitiligo is a complex disease causing a selective, often progressive, loss of functioning
      melanocytes from epidermal basal layer resulting in white patches on the skin and
      occasionally mucosae. Worldwide prevalence of vitiligo is around 1% whereas in India it is
      around 3-4% ranging from 0.46% to 8.8%.

      Etiopathogenesis of vitiligo is multifactorial consisting of genetic, immunological and
      environmental factors. Environmental and genetic factors act in concert to destroy
      melanocytes. Reactive oxygen species (ROS) play important roles in vitiligo pathology,but the
      autoimmune pathogenesis has been proposed as one of the main causes of vitiligo.

      Surgical methods, mainly transplantation of non cultured epidermal cell suspension are
      effective treatment for stable vitiligo. Transplantation of autologous noncultured epidermal
      cell suspension and non-cultured dermal cell suspension in combination (a mode of cellular
      grafting technique) is a novel surgical method for the treatment of vitiligo. Cytotoxic CD8+
      ( cluster of differentiation 8+) cells in vitiligo perilesions may dictate the fate of
      transplantation, and strategies against CD8+ T cell activation might be beneficial for
      patients undergoing melanocyte transplantation. Mesenchymal cells could inhibit T cell
      proliferation and induce T cell apoptosis. Bartsch first identified and characterized dermal
      mesenchymal cells (DMCs). They have a multi-lineage differentiation potential into
      adipocytes, osteocytes and chondrocytes.Vitiligo patients' autologous melanocytes
      transplantation efficiency may be predicted by perilesional skin-homing CD8+ T cell
      activities, and the immunoregulatory DMCs might be used as auxiliary agent to improve the
      efficacy.

      This pilot study is planned to compare transplantation of autologous noncultured epidermal
      cell suspension v/s its combination with non-cultured dermal cell suspension as a novel
      method in vitiligo surgery in stability of vitiligo with regards to extent of repigmentation,
      color matching of repigmented area, patient satisfaction and adverse events if any. This is
      the first study using transplantation of autologous noncultured epidermal cell suspension and
      non-cultured dermal cell suspension in combination as a new modality in vitiligo surgery.
Vitiligo, the most common depigmenting disorder is an 'idiopathic', acquired pigmentary
      disorder caused by the loss of functional melanocytes from the epidermis. The course of the
      disease is unpredictable but is often progressive with phases of stabilized depigmentation.
      It usually begins during childhood or young adulthood. Approximately one third to one half of
      the patients develops the disease before the age of 20 years. The presence of vitiligo on
      exposed areas of body leads to social embarrassment, psychological turmoil, and cosmetic
      disfigurement in those affected.

      Its prevalence is 1%, ranging from 0.1 to > 8.8% in different countries of the globe. Both
      sexes are equally affected although the greater number of reports among females is probably
      due to the greater social consequences to women and girls affected by this condition.

      Treatment options A number of therapeutic options for vitiligo are available but there is
      still a need for a treatment that is promptly effective. There is no curative treatment for
      this condition. Management of vitiligo is a real challenge for a dermatologist.

      Medical therapies:

      Corticosteroids (Topical, intralesional and systemic), Oral mini pulse, PUVA (topical and
      systemic), NBUVB, calcipotriol and tacrolimus are used most widely. Some of the less commonly
      used medical modalities include phenylalanine, khellin, topical minoxidil, levamisole and
      melagenina. Recently oral minocycline was shown to be effective in treating vitiligo.

      Most of these therapies aim to restore melanocyte function by their anti-inflammatory or
      immunomodulatory action and by preventing melanocyte auto destruction so that normal skin
      appearance and function is restored.

      Surgical therapies:

      All patients with vitiligo should be initially treated with medical methods. Surgical methods
      are important solutions for stable vitiligo refractory to medical treatment. High
      repigmentation rates are obtained with all procedures so far described in most anatomic
      locations, but they are of little help for acral areas and bony prominences. Unilateral
      vitiligo is the clinical form with the best response to grafting and transplant methods, and
      a good proportion of patients with stable bilateral disease also respond adequately.
      Nevertheless, appropriate patient selection is important to achieve maximal results.However
      none of the surgical modalities developed so far is uniformly effective in all patients and
      body sites and there is need for constant research and innovations for better surgical
      therapeutic options for vitiligo.

      Aims of various surgical procedures:

      A) Camouflage Tattooing: Introduction of artificial pigments into the lesions for permanent
      camouflage.

      B) Excision: Removal of the depigmented areas, e.g. excision with primary closure and
      covering with thin Thiersch's graft.

      C) Melanocyte transplantation: commonly used methods of autologous transplant of melanocytes
      are

      Tissue grafts:

        1. Thin and ultra-thin split thickness grafts (STSG)

        2. Suction blister epidermal grafts(SBEG)

        3. Mini punch grafts (MPG)

        4. Hair follicular grafts (HFG)

           Cellular grafts:

        5. Noncultured epidermal cell suspension (NCES)

        6. Cultured "pure" melanocytes (CM)

        7. Cultured epithelial grafts (CE)

        8. Autologous noncultured extracted hair follicle outer root sheath cell suspension also
           called follicular cell suspension (FCS) D) Therapeutically wounding the lesion to
           stimulate the melanocytes from the periphery and the black hair follicles to
           proliferate, migrate and re-pigment the lesion, e.g. therapeutic dermabrasion, laser
           ablation, cryosurgery (liquid nitrogen spraying), needling and local application of
           phenol or trichloroacetic acid.

      Every method has its own advantages and disadvantages. As there are no specific data
      available from the prospective studies in this field, it is not easy to recommend which
      surgical approach to vitiligo offers the best result.

      'Vitiligo global issues consensus conference, 2011' convened by Vitiligo European Task Force
      (VETF), concluded that assessment of 'overall' stability is inaccurate and unreliable,
      whereas individual lesion stability is more reliable, especially when used in the context of
      surgical intervention.

      Methods and Size of Lesions:

      Depending on the size of the treated area, the method may vary. Simple methods such as mini
      punch grafting and suction epidermal grafting are useful for small or medium sized lesions.
      On the contrary, for extensive depigmented defects, cellular transplants may be required.

      Age:

      Because of the invasive nature of surgical procedures, they are not recommended in children;
      nevertheless, highly motivated adolescents can be treated under sedation or general
      anesthesia. Also, it is not surprising to see patients beyond the age of 50 years who may be
      interested in surgical repigmentation.

      Psychological Aspects:

      Some patients with high emotional trauma because of depigmentation may seek advice for
      invasive procedures. However, a psychological evaluation may be needed to ascertain the real
      need for surgical treatment.

      Photographic Record:

      Illustrations are recommended to help in determining the percentage of improvement, quality
      of repigmentation and possible side effects.

      Patient's Expectations:

      Repigmentation is not always comparable with normally pigmented skin and the final results
      vary considerably from patient to patient. However, most individuals are pleased with the
      achieved results; minor imperfections are far less important than the noticeable
      repigmentation of vitiliginous skin, mainly in ethnic skin patients with a dark complexion;
      sometimes surgical repigmentation may look even better than what is observed in many patients
      after medical therapy.

      Method and Donor Site:

      Appropriate training with a specific method is an important prerequisite for surgical
      therapy. Donor site should be as hidden as possible and the gluteal region may be suitable
      for this purpose in most patients.

      Success rates of different surgical options:

      Among all procedures, suction blister epidermal grafts and thin and ultra-thin
      split-thickness grafts seem to be the most effective procedures, with overall success rates
      of 80.3% (CI 76.4-84.2%) and 77.9% (CI 72.2-83.6%) respectively. But, a recent randomized
      study directly comparing NCES and SBEG showed NCES is significantly better than SBEG. Among
      cellular grafts, all techniques seem to be equally effective with success rates of 61.1% (CI
      56.1-66.1%), 63.6% (CI 57.2-70%), and 63.6% (CI 55.8-70.6%) for noncultured epidermal cell
      suspension, cultured melanocytes and cultured epidermis respectively. The mean repigmentation
      with noncultured extracted outer root sheath cell suspension is about 65.7%).

      NONCULTURED EPIDERMAL CELL SUSPENSION The technique of noncultured epidermal suspension was
      pioneered by Gauthier et al. The suspension was prepared by incubating the donor skin
      obtained from the scalp in trypsin 0.25% for 18 hrs. The suspension was injected into
      blisters raised by cryotherapy. Eight out of the 12 patients treated had > 70% repigmentation
      at the vitiligo site. It was proposed that the presence of keratinocytes in the suspension
      supplies essential growth factors for melanocyte growth. They stated that this technique
      could emerge as simple and effective alternative to the costly cultured melanocyte
      transplantation technique.

      NON-CULTURED DERMAL CELL SUSPENSION

      Dermal mesenchymal cells were originally isolated from the dermis of juvenile and adult mice
      by Toma et al., afterwards, same group identified such a cell population in human skin. Georg
      Bartsch firstly identified and characterized dermal mesenchymal cells (DMCs). DMCs had
      multi-lineage differentiation potential into adipocytes, osteocytes and chondrocytes. The
      surface antigenic profile of DMCs was positive for CD90 but differs in regard to negativity
      for CD34.

      Zhou et al investigated the factors determining the efficiency of autologous melanocyte
      transplantation of vitiligo patients by focusing on perilesional skin homing CD8+ T
      lymphocytes, and studied the potential effects of dermal mesenchymal cells (DMCs) on CD8+ T
      cell activities in vitro. The patients with high number of perilesional CD8+ T cells were
      associated with poor repigmentation rate and a significant lesser number of CD8+ T cells was
      infiltrating in patients with excellent or good re-pigmentation responses. Also, skin homing
      CD8+ T cells proliferation was significantly inhibited when co-culture with DMCs at 1:1 ratio
      as the percentage of proliferative CD8+ T cells dropped from 94.72% to 39.50% (p,0.05) after
      DMCs co-culture. In the co-culture system, DMCs significantly inhibited skin homing CD8+ T
      proliferation and induced those cells apoptosis. These data confirm that DMCs induces
      significant immunosuppressive abilities against skin homing CD8+ T lymphocytes and may help
      improve the efficacy of melanocytes transplantation. Non-cultured Dermal Cell Suspension
      (NDCS) is a novel method to increase the efficacy of non-cultured epidermal cell suspension
      (NCES).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: extent of repigmentation
time frame: 6 months
description: Repigmentation will be assessed as follows -
≤25% Minimal repigmentation 26-50% Mild repigmentation 51-75% Moderate repigmentation 76-90% Marked repigmentation >90% Excellent repigmentation
measure: pattern of repigmentation
time frame: 6 months
description: diffuse peri follicular migrating from the borders
arm group label: Non cultured epidermal cell suspension
arm group type: Active Comparator
description: In 20 patients who have stable vitiligo with the duration of stability more than 3 months, non cultured epidermal cell suspension will be done. Patients will be divided into 2 subgroups of 10 patients each of stability duration of 3-6 months and more than 1 year respectively and non cultured epidermal cell suspension will be done.
arm group label: Non cultured dermal cell suspension
arm group type: Experimental
description: In 20 patients who have stable vitiligo with the duration of stability more than 3 months, combination of non cultured epidermal cell suspension and non cultured dermal cell suspension will be done. Patients will be divided into 2 subgroups of 10 patients each of stability duration of 3-6 months and more than 1 year respectively and combination of non cultured epidermal cell suspension and non cultured dermal cell suspension will be done.
intervention type: Procedure
intervention name: Non cultured epidermal cell suspension
description: Non cultured epidermal cell suspension Split thickness skin specimen will be transferred under aseptic conditions to a container with normal salineand transferred to laboratory. There, the skin graft will be transferred to Trypsin-EDTA solution (0.25% trypsin and 0.02% EDTA) in a Petri dish and incubated overnight at 4°C in 5% CO2 to separate the epidermis from the dermis.Afterwards, the Trypsin-EDTA solution will be removed and PBS will be added and pipetted well so as to separate the cells from the tissue.The suspension will be centrifuged at 1000 rpm for 5 minutes.The supernatant will then be discarded and Phosphate buffer saline is added to make suspension of non-cultured epidermal cells.
arm group label: Non cultured dermal cell suspension
arm group label: Non cultured epidermal cell suspension
intervention type: Procedure
intervention name: Non cultured dermal cell suspension
description: Non-cultured Dermal Cell Suspension Skin punch will be collected in phosphate buffer saline (PBS) with antibiotics (penicillin and streptomycin). The epidermis will be cut off from dermis carefully using a surgical blade (Epidermal part will be used for the epidermal cell suspension). Dermis will be then cut into small pieces and incubated in collagenase (1mg/ml) overnight at room temperature. Next day content will be diluted with PBS and centrifuged at 1000rpm for 5 minutes. Pellet will be washed three times with PBS to remove collagenase activity. Phosphate buffer saline is added to make suspension of non-cultured dermal cells and will be used for the autologous transplantation.
arm group label: Non cultured dermal cell suspension
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Davinder Parsad, MD
phone: 9736060361
phone ext: +91
email: parsad@me.com
facility: 
status: Recruiting
contact: 
country: India
responsible party type: Principal Investigator
investigator affiliation: Postgraduate Institute of Medical Education and Research
investigator full name: Davinder Parsad
investigator title: Professor
mesh term: Vitiligo
sharing ipd: No
submitted: February 21, 2018
returned: October 5, 2018