Pilot Study of Gut Commensals in Antiphospholipid Syndrome

NCT01787305 | Active Not Recruiting DMC

• 3 other identifiers: 1210010962U01AI101990R01AI118855-01
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to explore if certain commensals within the gut microbiota (the collection of all microbes that live inside the gut) correlate with autoantibodies in the autoimmune clotting disorder called antiphospholipid syndrome. The study hypothesis is that particular commensals induce the autoantibodies (immune molecules that bind to self structures) and thus correlate with the level of immune cells and antibodies that are self-reactive. Participants are patients with antiphospholipid syndrome and individuals who have tested positive on a prior blood test for anti-beta2-glycoprotein I antibodies or those that have tested negative for antiphospholipid antibodies in their blood, but had a clotting event or a health problem that puts them at risk to form blood clots.

Conditions

Antiphospholipid Syndrome (APS)

Keywords

microbiome; commensals; autoantibodies; autoreactive T cells

Outcome Measures

Primary Outcomes (3)

• Change in autoantibody levels

  Certain gut bacteria will correlate with anti-β2GPI autoantibody titers in anti-β2GPI-positive subjects that are lower or absent in aPL-negative subjects

  Baseline

• Change in autoantibody levels

  Certain gut bacteria will correlate with anti-β2GPI autoantibody titers in anti-β2GPI-positive subjects that are lower or absent in aPL-negative subjects

  4 weeks

• Change in autoantibody levels

  Certain gut bacteria will correlate with anti-β2GPI autoantibody titers in anti-β2GPI-positive subjects that are lower or absent in aPL-negative subjects

  8 weeks

Secondary Outcomes (3)

• Change in autoreactive T cell frequencies

  Baseline

• Change in autoreactive T cell frequencies

  4 weeks

• Change in autoreactive T cell frequencies

  8 weeks

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Yale New Haven Hospital and affiliated outpatient clinics Hospital for Special Surgery and affiliated outpatient clinics

You may qualify if:

• years of age
• One of the following groups below:
• Group 1a: Persistently positive anti-β2GPI on Coumadin (n: 10) Group 1b: Persistently positive anti-β2GPI not on Coumadin (n: 10) Group 2a: Negative aPL on Coumadin (n: 10) Group 2b: Negative aPL not on Coumadin (n: 10) Persistently positive aβ2GPI will be defined as anti-β2GPI immunoglobulin G (IgG)/IgM/IgA ≥ 40 SGU/SMU at two separate time points at least 12 weeks apart.
• Negative aPL will be defined as negative Lupus anticoagulant test, aCL IgG/IgM/IgA, and anti-β2GPI IgG/IgM/IgA within 12 months of the study entry.

You may not qualify if:

• Any autoimmune diseases including Rheumatoid Arthritis, Spondylarthropathy, Inflammatory Muscle Disease, and Sarcoidosis
• Steroid use greater than 10 mg/d prednisone or equivalent 30 days prior to enrollment
• Any immunosuppressive drug use within 3 months prior to screening (mycophenolate mofetil, azathioprine, methotrexate, leflunomide, rituximab, cyclophosphamide, intravenous immunoglobulin, plasmapheresis).
• Ongoing chronic infection (viral, bacterial or fungal) including known HIV, Hepatitis B/C
• Acute infection receiving any antibiotics within 30 days prior to screening
• Acute thrombosis within 2 days prior to screening
• 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
• Celiac Disease diagnosed by biopsy
• Bulimia or anorexia nervosa
• Probiotics (greater than estimated 10\^9 cfu or organisms per day) within 30 days prior to enrollment (with the exception of fermented beverages, milks or yogurts).
• Morbid obesity (BMI ≥ 40)
• Diabetes Mellitus Type I or II 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)

Sponsors & Collaborators

• Yale University: lead
• Hospital for Special Surgery, New York: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Yale University School of Medicine; Yale-New Haven Hospital

New Haven, Connecticut, 06511, United States

Location

Related Publications (2)

• 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.

  PMID: 32457482 BACKGROUND

• 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.

  PMID: 31227334 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood Serum Stool DNA?

MeSH Terms

Conditions

Antiphospholipid Syndrome

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases

Study Officials

• Martin A Kriegel, MD PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2013
• First Posted: February 8, 2013
• Study Start: February 1, 2013
• Primary Completion: January 1, 2017
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 13, 2025

Record last verified: 2025-08

Locations

US (1)