Metabolic Profiling of Immune Responses in Immune-mediated Diseases

Psoriasis Clinical Trial

Official title:

Metabolic Profiling of Immune Responses in Immune-Mediated Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04864886
• Other study ID #: 10000392
• Secondary ID: 000392-I
• Status: Recruiting
• Start date: August 10, 2021
• Est. completion date: June 30, 2027

Study information

• Verified date: March 26, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Ashleigh A Sun
• Phone: (301) 605-2896
• Email: sunaa[@]niaid.nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background:

The immune system is the part of the body that fights infection. Some people have immune deficiencies that cause skin rashes, make them get sick often with infections, or make it difficult for their skin to heal. Researchers want to learn more to better treat conditions that affect immune response.

Objective:

To learn about how the immune system and skin healing are related to each other.

Eligibility:

People ages 18-75 with primary immune deficiency, eczema, or psoriasis. Healthy volunteers are also needed.

Design:

Participants will be screened with a medical and medicine history and a physical exam. They may take a pregnancy test.

Participants will discuss the medicines or supplements they take as well as skin products they use, such as soaps and lotions.

Participants will have up to 4 skin biopsies taken from the forearm. A needle will inject an anesthetic into the skin where the biopsy will be done. A sharp tool that looks like a tiny cookie cutter will be used to remove a round plug of skin a bit smaller than the tip of a pencil.

Participants will give at least 1 blood sample.

Participants may have optional skin swab collection. A cotton swab will be used to swab the skin on the arm.

Participants may have optional skin tape collection. A sticky strip of tape will be placed on the arm and then removed.

Participants may give leftover samples taken as part of their regular medical care.

Participation will last for about 4 days. Participants will have 2 visits that each last about 1 hour. They may be asked to repeat the study in the future.

Description:

Study Description:

This is an exploratory sample collection study enrolling adult healthy volunteers and patients with immune-mediated diseases to elucidate the metabolic signatures associated with immune-mediated diseases. We hypothesize that activation of, and responses to, specific immune pathways will require metabolic changes within cells, serum, and skin.

Following screening and baseline procedures, including blood draw, participants will undergo skin biopsies. The skin biopsies will involve up to 4 biopsies: 2 initial punch biopsies 2 mm in diameter, optionally followed by 1 or 2 punch biopsies 3 (+/-1) days later using a 3-mm punch to encompass the initial biopsy site(s), capturing the tissue at 3 days of healing. In addition, skin swabs and tape strips may be collected to assess for microbial or host markers of epithelial repair. Peripheral blood will be collected with the initial biopsies to compare metabolic signatures in peripheral blood cells and serum with those in the skin. After day 1 (or 3, if the participant has that optional visit), participation in the study will be complete. Samples and data will be stored for future research use.

Objectives:

Primary Objectives:

1. Evaluate metabolic profiles in immune activation associated with known or suspected immune-mediated disorders.

2. Determine whether there are abnormalities in specific tissue repair pathways, such as epithelial to mesenchymal transition (EMT), that are associated with immune-mediated disorders.

Secondary Objectives:

Not applicable.

Endpoints:

Primary Endpoints:

1. Fold differences in metabolic pathways associated with immune pathways.

2. Fold differences in metabolic pathways related to wound healing.

3. Change in relative abundance of microbial skin taxa and/or skin metabolites associated with wound healing or immune-mediated disorders.

Secondary Endpoints:

Not applicable.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Meets one of the following:

1. Has documentation of PID confirmed by genetic evaluation demonstrating a deleterious variant in the gene (or genes) known to be associated with immune deficiency (confirmed PID); or

2. Has documented variant of undetermined significance in a gene (or genes) that is predicted to be deleterious in immune function by the investigators AND a clinical history of infections which are more frequent, more chronic, or more severe than normal (suspected PID); or

3. Has physician-diagnosed psoriasis; or

4. Has physician-diagnosed AD; or

5. Does not have clinically apparent evidence of any monogenic or digenic immune defect, AD, or psoriasis (healthy volunteers).

2. Aged 18 to 75 years.

3. Willing to allow storage of blood, biopsy tissue, and bacterial and fungal cultures for future research.

4. Able to provide informed consent.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Current or prior (within 3 months) anticoagulant or anti-platelet therapy (other than aspirin or non-steroidal anti-inflammatory drugs).

2. Current or prior (within 3 months) use of immunomodulatory drugs (eg, chemotherapy, steroids), except if approved by the principal investigator.

3. History of keloid formation.

4. Pregnancy, lactating, or breastfeeding.

5. Any condition that, in the opinion of the investigator, contraindicates participation in the study.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema
• Immunologic Deficiency Syndromes
• Primary Immunodeficiency
• Primary Immunodeficiency Diseases
• Psoriasis

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Dmitrieva NI, Walts AD, Nguyen DP, Grubb A, Zhang X, Wang X, Ping X, Jin H, Yu Z, Yu ZX, Yang D, Schwartzbeck R, Dalgard CL, Kozel BA, Levin MD, Knutsen RH, Liu D, Milner JD, Lopez DB, O'Connell MP, Lee CR, Myles IA, Hsu AP, Freeman AF, Holland SM, Chen G, Boehm M. Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome. J Clin Invest. 2020 Aug 3;130(8):4167-4181. doi: 10.1172/JCI135490. — View Citation

McCann KJ, Yadav M, Alishahedani ME, Freeman AF, Myles IA. Differential responses to folic acid in an established keloid fibroblast cell line are mediated by JAK1/2 and STAT3. PLoS One. 2021 Mar 4;16(3):e0248011. doi: 10.1371/journal.pone.0248011. eCollection 2021. — View Citation

Myles IA, Castillo CR, Barbian KD, Kanakabandi K, Virtaneva K, Fitzmeyer E, Paneru M, Otaizo-Carrasquero F, Myers TG, Markowitz TE, Moore IN, Liu X, Ferrer M, Sakamachi Y, Garantziotis S, Swamydas M, Lionakis MS, Anderson ED, Earland NJ, Ganesan S, Sun AA, Bergerson JRE, Silverman RA, Petersen M, Martens CA, Datta SK. Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair. Sci Transl Med. 2020 Sep 9;12(560):eaaz8631. doi: 10.1126/scitranslmed.aaz8631. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in relative abundance of microbial skin taxa and/or skin metabolites associated with wound healing or immune mediated disorders.	Determine whether there are abnormalities in specific tissue repair pathways, such as epithelial to mesenchymal transition (EMT) are associated with immune-mediated disorders.	Throughout study
Primary	Fold difference in metabolic pathways associated with immune pathways.	Evaluate metabolic profiles in immune activation associated with known or suspected immune-mediated disorders.	Throughout study
Primary	Fold differences in metabolic pathways related to wound healing.	Determine whether there are abnormalities in specific tissue repair pathways, such as epithelial to mesenchymal transition (EMT) are associated with immune-mediated disorders.	Throughout study

External Links

•   NIH Clinical Center Detailed Web Page