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Dendritic Cells in Patients With Acute or Chronic Skin Graft Versus Host Disease

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ClinicalTrials.gov Identifier: NCT02611180
Recruitment Status : Recruiting
First Posted : November 20, 2015
Last Update Posted : February 28, 2019
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:

Dendritic cells (DCs) serve as sentries for the immune system. DCs recognize foreign compounds (antigens) in the body, which they internalize and process. When DCs uptake foreign antigens, they migrate to secondary lymphoid organs, where the processed antigens are presented to T cells.

Various DC subsets with unique cell lineages, surface protein markers, and tissue localization determinants have been identified. For example, Langerhans cells (LCs) and interstitial dendritic cells (intDCs) are DCs found in stratified epithelia, such as the skin. Though both are expressed in the skin, they differ with respect to their origin and surface protein content and can activate distinct types of immune responses. They may also have different specificities for the capture of antigens and presentation to circulating T cells.

To date, it is unknown what role, if any, the different DC populations that reside or repopulate in the skin play in the development and progression of skin graft-versus-host disease (GVHD) following bone marrow transplant.


Condition or disease Intervention/treatment
Acute Graft-versus-host Disease Acute GVHD Chronic Graft-versus-host Disease Chronic GVHD Procedure: Skin punch biopsy Procedure: Peripheral blood draw

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Analysis of Dendritic Cells in Patients With Acute or Chronic Skin Graft Versus Host Disease
Actual Study Start Date : April 30, 2015
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : April 30, 2020


Group/Cohort Intervention/treatment
Arm 1: Acute skin GVHD
  • When clinically indicated, patients will undergo a skin biopsy to confirm a suspected diagnosis of acute or chronic GVHD, or to assess the status of their previously diagnosed acute or chronic GVHD. After the necessary samples are obtained for optimal medical care of the patient, two 6 mm punch biopsies (or four 4 mm punch biopsies) will be performed for research purposes, one (or two) of the affected area and one (or two) of a non-affected area (normal skin).
  • Patients who have clinical resolution of their acute or chronic GVHD will undergo one additional 6 mm punch biopsy (or two additional 4 mm punch biopsies) of the previously affected area. This additional biopsy should occur within 10 cm of the previous affected area sample.
  • With each skin biopsy, peripheral blood will be obtained by venipuncture or cannulation of an indwelling venous access device.
Procedure: Skin punch biopsy
Procedure: Peripheral blood draw
Arm 2: Chronic skin GVHD
  • When clinically indicated, patients will undergo a skin biopsy to confirm a suspected diagnosis of acute or chronic GVHD, or to assess the status of their previously diagnosed acute or chronic GVHD. After the necessary samples are obtained for optimal medical care of the patient, two 6 mm punch biopsies (or four 4 mm punch biopsies) will be performed for research purposes, one (or two) of the affected area and one (or two) of a non-affected area (normal skin).
  • Patients who have clinical resolution of their acute or chronic GVHD will undergo one additional 6 mm punch biopsy (or two additional 4 mm punch biopsies) of the previously affected area. This additional biopsy should occur within 10 cm of the previous affected area sample.
  • With each skin biopsy, peripheral blood will be obtained by venipuncture or cannulation of an indwelling venous access device.
Procedure: Skin punch biopsy
Procedure: Peripheral blood draw



Primary Outcome Measures :
  1. Dendritic cell characteristics [ Time Frame: Up to 2 years ]
    • Both GVHD affected and unaffected skin sections will be analyzed by immunostaining and the types of cells and strains of skin microbiota present will be analyzed
    • The different isolated DCs will be activated by different stimuli and will be characterized by gene (DNA, RNA sequencing or arrays) and multicolor flow cytometry analysis.

  2. Antigen specific lymphocyte subset characteristics [ Time Frame: Up to 2 years ]
    • Both GVHD affected and unaffected skin sections will be analyzed by immunostaining and the types of cells and strains of skin microbiota present will be analyzed
    • CD4+ and CD8+ T cells or other lymphocyte populations will be isolated from peripheral blood by fluorescence activated cell sorting. The DC subsets purified from the skin tissue will be used to stimulate these T cell populations. This will be followed by thorough characterization of the charged T cell populations by a variety of methods. These will include assays to measure proliferation, gene array analysis cytokine secretion and other functions of the charged T cells.

  3. Genes and skin microbiota that correlate with dendritic cell function [ Time Frame: Up to 2 years ]
  4. Potential treatment targets as measured by deep sequencing or microarray analysis [ Time Frame: Up to 2 years ]

Biospecimen Retention:   Samples With DNA
Skin samples and blood samples


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with current or suspected acute or chronic GVHD of the skin
Criteria

Inclusion Criteria:

  • At least 18 years of age at enrollment
  • Willing and able to sign the informed consent
  • Current diagnosis/suspected diagnosis of acute skin GVHD OR Current diagnosis/suspected diagnosis of chronic skin GVHD

Exclusion Criteria:

  • Known infection with Hepatitis B or C, HTLV, or HIV
  • Pregnant females

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02611180


Contacts
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Contact: Eynav Klechevsky, Ph.D. 314-286-0897 eklechevsky@wustl.edu
Contact: Caroline Bumb 314-362-7249 cbumb@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Eynav Klechevsky, Ph.D.    314-286-0897    eklechevsky@wustl.edu   
Contact: Caroline Bumb    314-362-7249    cbumb@wustl.edu   
Principal Investigator: Eynav Klechevsky, Ph.D.         
Sub-Investigator: Mark Schroeder, M.D.         
Sub-Investigator: Camille Abboud, M.D.         
Sub-Investigator: Milan Anadkat, M.D.         
Sub-Investigator: Amanda Cashen, M.D.         
Sub-Investigator: John F DiPersio, M.D., Ph.D.         
Sub-Investigator: Kyle Eash, M.D.         
Sub-Investigator: Todd Fehniger, M.D., Ph.D.         
Sub-Investigator: Armin Ghobadi, M.D.         
Sub-Investigator: Meagan Jacoby, M.D., Ph.D.         
Sub-Investigator: Caroline Mann, M.D.         
Sub-Investigator: Amy Musiek, M.D.         
Sub-Investigator: Iskra Pusic, M.D.         
Sub-Investigator: Rizwan Romee, M.D.         
Sub-Investigator: Keith Stockerl-Goldstein, M.D.         
Sub-Investigator: Michael Tomasson, M.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Ravi Vij, M.D.         
Sub-Investigator: Matthew Walter, M.D.         
Sub-Investigator: John Welch, M.D., Ph.D.         
Sub-Investigator: Peter Westervelt, M.D., Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Eynav Klechevsky, Ph.D. Washington University School of Medicine

Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02611180     History of Changes
Other Study ID Numbers: 201405065
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases