Skin Immunity Sample Collection Involving Blisters and Biopsies

NCT03921515 | Withdrawn Early Phase 1

• 2 other identifiers: 19008419-I-0084
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The way the body heals and protects itself from getting sick is called the immune response. Some people with weak immune systems get sick often or get rashes and skin infections. Researchers want to find out how the immune system and skin problems are related so they can help these people. Objective: To learn about how immune response and skin healing are related to each other. Eligibility: People ages 18-65 with hyper IgE syndrome or Job syndrome or people ages 7-65 with chronic granulomatous disease. Healthy volunteers ages 18 65 are also needed. Design: Participants will be screened with: Medical history Physical exam Possible urine tests Participants will have 1 to 3 visits within about a week. Visits will include the following: Participants will have a wells device strapped to the inside of the forearm. It will suction the skin and pull the top layer away to form 8 blisters. The skin over the blisters and the liquid inside will be collected. Participants will have up to 4 skin biopsies. A sharp tool will remove a small plug of skin from the forearm. Participants may have blood and urine tests. The skin on participants skin will be rubbed with a cotton swab. Some participants will have an overnight visit. They will have the blister device placed back on the arm. The wells will be lined up over the blister wounds. The wells will be filled with either saline or the participant s blood serum. The device will be covered and left on the arm for up to 24 hours. Doctors will periodically remove some liquid from the wells.

Conditions

Hyper-Immunoglobulin E. Syndrome (HEIS); Chronic Granulomatous Disease (CGD)

Keywords

Hyper-Immunuglobulin E.Syndrome; Chronic Granulomatous Disease; Tumor Necrosis Factor Alpha; Staphylococcus Aureus

Outcome Measures

Primary Outcomes (3)

• Tumor necrosis factor alpha (TNFa) production by keratinocytes from patients with HIES versus healthy volunteers

  Evaluate epithelial cell responses to cutaneous wounds and infections of keratinocytes and other cutaneous epithelial cells in patients with HIES or CGD and healthy volunteers.

  Throughout study

• T-cell infiltration as percent of total cell infiltration in patients with CGD versus healthy volunteers.

  Identify cellular mediators that contribute to the inflammatory processthrough evaluation of infiltrating cell types.

  Throughout study

• Fold induction in genes related to wound healing.

  Determine whether there are abnormalities in specific tissue repair pathways, such as epithelial to mesenchymal transition (EMT).

  Throughout study

Study Arms (2)

1

OTHER

Blister Induction

Other: Blister induction

2

OTHER

Skin Biopsies

Other: Skin Biopsies

Interventions

Blister induction OTHER

Blister induction involves creating 8 blisters on the forearm and removing the tops of the blisters for primary cell culture derivation. After blister induction, subjects may have an optional overnight admission to assess cell infiltration in response to autologous serum and/or sterile saline solution.

1

Skin Biopsies OTHER

The skin biopsies will involve up to 4 biopsies: 2 initial punch biopsies 2 mm in diameter, followed by a punch biopsy 3 (plus or minus 1) and 7 (plus or minus 2) days later using a 3 mm punch to encompass the initial biopsy sites, capturing the tissue at 3 and 7 days of healing.

2

Eligibility Criteria

• Age: 7 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets one of the following:
• has documentation of HIES or CGD (patient populations); or
• does not have clinically apparent evidence of an immune defect or history of invasive or recurrent S. aureus infections (healthy volunteers).
• Between the following age limits (inclusive):
• and 65 years old for healthy volunteers;
• and 65 years old for patients with CGD;
• and 65 years old for patients with HIES.
• Willing to allow storage of blood, RNA, bacterial and fungal cultures, and other tissue samples for future research.
• Able to provide informed consent.

You may not qualify if:

• For individuals undergoing blister or skin biopsy procedures, history of keloid formation.
• Current or prior (within 3 months) anticoagulant or anti-platelet therapy (other than aspirin or non-steroidal anti-inflammatory drugs \[NSAIDs\]).
• Current or prior (within 3 months) use of immunomodulatory drugs (e.g., chemotherapy, steroids), except if approved by the principal investigator.
• Pregnancy.
• Any condition that, in the opinion of the investigator, contraindicates participation in the study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763-71. doi: 10.1001/jama.298.15.1763.

  PMID: 17940231 BACKGROUND

• Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J, Johnson SK, Vandenesch F, Fridkin S, O'Boyle C, Danila RN, Lynfield R. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003 Dec 10;290(22):2976-84. doi: 10.1001/jama.290.22.2976.

  PMID: 14665659 BACKGROUND

• Myles IA, Datta SK. Staphylococcus aureus: an introduction. Semin Immunopathol. 2012 Mar;34(2):181-4. doi: 10.1007/s00281-011-0301-9. Epub 2012 Jan 27. No abstract available.

  PMID: 22282052 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Granulomatous Disease, Chronic; Staphylococcal Infections

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Ian A Myles, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2019
• First Posted: April 19, 2019
• Study Start: December 9, 2024
• Primary Completion: December 10, 2024
• Study Completion: December 10, 2024
• Last Updated: December 13, 2024

Record last verified: 2024-12

Locations

US (1)