The Human Microbiome in Immune-Mediated Diseases

Autoimmune Clinical Trial

Official title:

The Human Microbiome in Immune-Mediated Diseases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02394964
• Other study ID #: 1408014402
• Secondary ID: U01AI101990R01AI
• Status: Completed
• Start date: November 2014
• Est. completion date: December 2023

Study information

• Verified date: December 2023
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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 for pilot study (subjects enrolled in the exploratory mechanistic study arm will not be required to meet exclusion criteria and may be enrolled if the investigators believe that the subject can help address the scientific aim)..

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

Related Conditions & MeSH terms

• Autoimmune

Intervention

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

Locations

Country	Name	City	State
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Hospital for Special Surgery	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Yale University	Arthritis Foundation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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 autoa — View Citation

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 — View Citation

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 — View Citation

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. — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in Commensal bacteria	Difference in disease group vs. control commensal bacteria will be compared by looking at the relative abundances of the microbiota	8 weeks
Secondary	Immune Cross-reactivity with commensal bacteria	T and B cells in patients with immune-mediated diseases will cross react with specific microbial antigens	8 weeks