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Pilot Study of Gut Commensals in Antiphospholipid Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01787305
Recruitment Status : Active, not recruiting
First Posted : February 8, 2013
Last Update Posted : April 26, 2022
Sponsor:
Collaborators:
Hospital for Special Surgery, New York
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Yale University

Study Description
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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.

Condition or disease
Antiphospholipid Syndrome (APS)

Detailed Description:

Antiphospholipid syndrome (APS) is an autoimmune disorder in which people are at risk to form blood clots. Having a positive antiphospholipid antibody (aPL) test does not mean the person has APS; but a small number of people do develop APS. These antibodies can also occur in otherwise healthy people. We believe certain bacteria in the gut may cause these antibodies to be produced.

Current treatments in APS target the blood clotting system and the goal is to prevent future blood clots. Many patients require this therapy for their entire life. If an persistent trigger can be found within the gut microbiota, it may help in developing other treatments. This study is being conducted at two centers, Yale University School of Medicine in New Haven, CT, and The Hospital for Special Surgery in Manhattan, New York. We expect to enroll a total of 40 subjects in this study at these study sites.

Visits will be as follows:

Visit 1: Initial screening visit: Review of medical records and questionnaire completion.

Visit 2 (one month after initial visit) & Visit 3 (2 months after initial visit): Questionnaire relating to any changes that may have taken place since recruitment. Brief physical examination by the study doctor.

Overall participation: Over a period of 8 weeks.

Sample Collection:

At each study visit, a sample of blood will be obtained (approximately 6.5 tablespoons of whole blood) via one needle stick.

A take-home stool sample collection kit will be provided. Stool samples will be obtained within 24 hours before or after blood collection and delivered (or mailed) to a study site. 2 kits will be provided at the initial visit, 1 kit will be provided at the follow up visit at month 1.

Study Design
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Study Type : Observational
Estimated Enrollment : 16 participants
Observational Model: Case-Control
Time Perspective: Other
Official Title: Longitudinal Study of the Fecal Microbiome in Persistently Anti-β2 Glycoprotein-I Positive Individuals and Patients With Antiphospholipid Syndrome
Study Start Date : February 2013
Actual Primary Completion Date : January 2017
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. Change in autoantibody levels [ Time Frame: Baseline ]
    Certain gut bacteria will correlate with anti-β2GPI autoantibody titers in anti-β2GPI-positive subjects that are lower or absent in aPL-negative subjects

  2. Change in autoantibody levels [ Time Frame: 4 weeks ]
    Certain gut bacteria will correlate with anti-β2GPI autoantibody titers in anti-β2GPI-positive subjects that are lower or absent in aPL-negative subjects

  3. Change in autoantibody levels [ Time Frame: 8 weeks ]
    Certain gut bacteria will correlate with anti-β2GPI autoantibody titers in anti-β2GPI-positive subjects that are lower or absent in aPL-negative subjects


Secondary Outcome Measures :
  1. Change in autoreactive T cell frequencies [ Time Frame: Baseline ]
    Certain gut bacteria will correlate with β2GPI-reactive CD4+ T-cells in anti-β2GPI-positive subjects that are lower or absent in aPL-negative subjects.

  2. Change in autoreactive T cell frequencies [ Time Frame: 4 weeks ]
    Certain gut bacteria will correlate with β2GPI-reactive CD4+ T-cells in anti-β2GPI-positive subjects that are lower or absent in aPL-negative subjects.

  3. Change in autoreactive T cell frequencies [ Time Frame: 8 weeks ]
    Certain gut bacteria will correlate with β2GPI-reactive CD4+ T-cells in anti-β2GPI-positive subjects that are lower or absent in aPL-negative subjects.


Biospecimen Retention:   Samples With DNA
Whole Blood Serum Stool DNA?

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Yale New Haven Hospital and affiliated outpatient clinics Hospital for Special Surgery and affiliated outpatient clinics
Criteria

Inclusion Criteria:

  • 18-70 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.

Exclusion Criteria:

  • 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)
  • Known alcohol abuse
  • Pregnancy
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01787305


Locations
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United States, Connecticut
Yale University School of Medicine; Yale-New Haven Hospital
New Haven, Connecticut, United States, 06511
Sponsors and Collaborators
Yale University
Hospital for Special Surgery, New York
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Martin A Kriegel, MD PhD Yale University
More Information
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Publications of Results:

Other Publications:

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01787305    
Other Study ID Numbers: 1210010962
U01AI101990 ( U.S. NIH Grant/Contract )
R01AI118855-01 ( U.S. NIH Grant/Contract )
First Posted: February 8, 2013    Key Record Dates
Last Update Posted: April 26, 2022
Last Verified: April 2022
Keywords provided by Yale University:
microbiome
commensals
autoantibodies
autoreactive T cells
Additional relevant MeSH terms:
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Antiphospholipid Syndrome
Syndrome
Disease
 Pathologic Processes
Autoimmune Diseases
Immune System Diseases