The Human Microbiome in Immune-Mediated Diseases

NCT ID: NCT02394964

Last Updated: 2023-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

75 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-11-30

Study Completion Date

2023-12-31

Brief Summary

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The immune system is influenced by the commensal microbes that live in the gut and on the skin. This study aims to characterize the microbiota of subjects with autoimmune disease in order to determine whether certain microbial species may cause or worsen immune-mediated diseases

Detailed Description

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This is a combination of a defined pilot microbiome study as well as exploratory mechanistic research with candidate commensals identified based on known structures accessible in public databases. In the observational prospective two-center study, subjects will be followed for 8 weeks. The study will consist of a total of 3 study visits (0, 4 and 8 weeks). Screening and baseline visits (week 0) will take place at the same time. A study window period of +/- 7 days will be allowed for follow-up study visits. The mechanistic in vitro research with subjects' blood cells and candidate commensals will typically require between 2-4 visits for sampling, but will not be limited by the frequency of visits.

Conditions

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Autoimmune

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Systemic Lupus Erythematosus

Blood, stool, and swab samples will be collected at baseline, week 4, and week 8 and compared with control samples

Sample Collection

Intervention Type OTHER

Sample collection of blood, stool, and buccal and skin swab samples will be collected at baseline, week 4, and week 8

Subacute Cutaneous Lupus Erythematosus

Blood, stool, and swab samples will be collected at baseline, week 4, and week 8 and compared with control samples

Sample Collection

Intervention Type OTHER

Sample collection of blood, stool, and buccal and skin swab samples will be collected at baseline, week 4, and week 8

Control

Blood, stool, and swab samples will be collected for comparison to each disease group

Sample Collection

Intervention Type OTHER

Sample collection of blood, stool, and buccal and skin swab samples will be collected at baseline, week 4, and week 8

Cutaneous T-Cell Lymphoma

Blood and swab samples will be collected for comparison to each disease group

Sample Collection

Intervention Type OTHER

Sample collection of blood, stool, and buccal and skin swab samples will be collected at baseline, week 4, and week 8

Autoimmune Disorders

Blood, stool, and swab samples will be collected for comparison to each disease group

Sample Collection

Intervention Type OTHER

Sample collection of blood, stool, and buccal and skin swab samples will be collected at baseline, week 4, and week 8

Interventions

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Sample Collection

Sample collection of blood, stool, and buccal and skin swab samples will be collected at baseline, week 4, and week 8

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 18 years of age and older
* Diagnosis of an immune-mediated disease by a healthcare provider, including but not limited to: systemic lupus erythematosus, subacute cutaneous lupus erythematosus

Exclusion Criteria

* Ongoing chronic infection (viral, bacterial or fungal) including known HIV, Hepatitis B/C
* Acute infection receiving any antibiotics or any use of antibiotics within 90 days prior to screening
* For skin swab collection (see also appendix D):

* No use of topical antibiotics within 7-days prior to collection of swab, other than use in normal hand washing.
* No use of topical antimicrobial products (as outlined in appendix F) within 48 hours prior to collection of swab
* Subject must not have bathed within 8-hours of swab collection.
* For oral swab collection (see also appendix D):

* No use of antiseptic mouth washes (as outlined in appendix F) within 48 hours of swab collection
* Subjects must not have brushed teeth or flossed within 8-hours of swab collection
* Major gastrointestinal surgery less than 5 years prior to enrollment (with the exception of appendectomy)
* Any Gastrointestinal bleeding history
* Inflammatory Bowel Disease diagnosed by biopsy
* Bulimia or anorexia nervosa
* Probiotics (greater than estimated 109 cfu or organisms per day) within 90 days prior to enrollment (with the exception of fermented beverages, milks or yogurts).
* Morbid obesity (BMI ≥ 40)
* Type I Diabetes Mellitus
* Diabetes Mellitus type 2, poorly controlled defined as Hgb A1c greater than 8% on medical therapy
* Malignancy within one year prior to screening (with the exception of non-metastatic squamous or basal cell skin carcinomas and cervical carcinoma if received curative surgical treatment)
* Known illicit drug or alcohol abuse
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Arthritis Foundation

OTHER

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martin Kriegel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

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Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Hospital for Special Surgery

New York, New York, United States

Site Status

Countries

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United States

References

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Ruff WE, Greiling TM, Kriegel MA. Host-microbiota interactions in immune-mediated diseases. Nat Rev Microbiol. 2020 Sep;18(9):521-538. doi: 10.1038/s41579-020-0367-2. Epub 2020 May 26.

Reference Type BACKGROUND
PMID: 32457482 (View on PubMed)

Zegarra-Ruiz DF, El Beidaq A, Iniguez AJ, Lubrano Di Ricco M, Manfredo Vieira S, Ruff WE, Mubiru D, Fine RL, Sterpka J, Greiling TM, Dehner C, Kriegel MA. A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity. Cell Host Microbe. 2019 Jan 9;25(1):113-127.e6. doi: 10.1016/j.chom.2018.11.009. Epub 2018 Dec 20.

Reference Type RESULT
PMID: 30581114 (View on PubMed)

Ruff WE, Dehner C, Kim WJ, Pagovich O, Aguiar CL, Yu AT, Roth AS, Vieira SM, Kriegel C, Adeniyi O, Mulla MJ, Abrahams VM, Kwok WW, Nussinov R, Erkan D, Goodman AL, Kriegel MA. Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity. Cell Host Microbe. 2019 Jul 10;26(1):100-113.e8. doi: 10.1016/j.chom.2019.05.003. Epub 2019 Jun 18.

Reference Type RESULT
PMID: 31227334 (View on PubMed)

Greiling TM, Dehner C, Chen X, Hughes K, Iniguez AJ, Boccitto M, Ruiz DZ, Renfroe SC, Vieira SM, Ruff WE, Sim S, Kriegel C, Glanternik J, Chen X, Girardi M, Degnan P, Costenbader KH, Goodman AL, Wolin SL, Kriegel MA. Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Sci Transl Med. 2018 Mar 28;10(434):eaan2306. doi: 10.1126/scitranslmed.aan2306.

Reference Type RESULT
PMID: 29593104 (View on PubMed)

Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018 Mar 9;359(6380):1156-1161. doi: 10.1126/science.aar7201.

Reference Type RESULT
PMID: 29590047 (View on PubMed)

Zhou H, Balint D, Shi Q, Vartanian T, Kriegel MA, Brito I. Lupus and inflammatory bowel disease share a common set of microbiome features distinct from other autoimmune disorders. Ann Rheum Dis. 2025 Jan;84(1):93-105. doi: 10.1136/ard-2024-225829. Epub 2025 Jan 2.

Reference Type DERIVED
PMID: 39874239 (View on PubMed)

Other Identifiers

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U01AI101990

Identifier Type: NIH

Identifier Source: secondary_id

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R01AI118855-01

Identifier Type: NIH

Identifier Source: secondary_id

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1408014402

Identifier Type: -

Identifier Source: org_study_id