T and B Cell Responses in Autoimmune Diseases

Terminated

• Conditions: Psoriasis; Arthritis, Rheumatoid; Crohn's Disease; Type 1 Diabetes Mellitus; Multiple Sclerosis

• Registration Number: NCT01947036
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

The study aims to establish whether defects in immune cell function are shared across multiple autoimmune diseases and whether those problems match to similar genes in the cells.

Detailed Description

This is a non-randomized, multi-center clinical research study. Subjects who are healthy or have a confirmed or suspected diagnosis of type 1diabetes, multiple sclerosis, psoriasis, Crohn's disease, or rheumatoid arthritis will be asked to donate a blood sample. No follow-ups are planned.

Investigators will:

* evaluate immune cells from subjects enrolled in this study and match the differences to types of immune cells known to cause autoimmune diseases

* investigate a particular disease pathway: the IL23R signaling cascade.

Study Timeline

• Study First Submitted: 2013-09-16
• Study First Submitted QC: 2013-09-16
• Study First Posted: 2013-09-20
• Study Start: 2014-01
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-24
• Last Update Posted: 2016-10-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

-Subject or subject's parent or legal guardian has provided written informed consent

-For healthy donors: Healthy individuals between 18 and 60 years of age, inclusive

• For all subjects with an autoimmune disease:

  1. Adults between 18 and 60 years, inclusive, diagnosed with or suspected of having one of the following five diseases: adult forms of rheumatoid arthritis (RA), type 1 diabetes (T1D, T1DM), multiple sclerosis (MS), Crohn's disease (CD), Psoriasis (Ps)

  2. Or Children from 8 years up to 18 years inclusive, diagnosed with or suspected of having type 1 diabetes (TID) or Crohn's disease (CD)

  3. Treatment naïve except for prednisone (or equivalent corticosteroid) <\=10mg/day

     4. For subjects diagnosed with type 1 diabetes:
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  1. Clinical diagnosis or suspected diagnosis of T1D

  2. Positive per standard clinical titer levels for anti-insulin antibodies if within 10 days of diagnosis (new-onset T1D); and otherwise one of the following antibodies-anti-GAD65, anti-ICA512/IA2 or anti-ZnT8

  3. Minimum body weight 17kg (≥37.5 pounds)

  4. Disease duration within 1 year

     5. For subjects diagnosed with multiple sclerosis:

  a. EDSS (Expanded Disability Status Scale) 0-5 b. Diagnosis or suspected diagnosis of MS as per Dr. Polman et al. Annals of Neurology 2010 c. Disease duration within 1 year

  6. For subjects diagnosed with rheumatoid arthritis (RA):

  a. Diagnosis or suspected diagnosis of RA (2010 ACR criteria) b. Anti-CCP antibody positive c. Disease duration within 1 year

  7. For subjects diagnosed with Crohn's disease:

  a. Clinical diagnosis or suspected diagnosis of Crohn's confirmed by endoscopy b. Disease duration within 1 year c. Minimum body weight 17 kg (≥37.5 pounds)

  8. For subjects diagnosed with psoriasis:
  9. Psoriasis diagnosis by a dermatologist
  10. Disease duration within 1 year
  11. At least two psoriatic plaques or a single plaque occupying at least 1% of total body surface outside scalp

Exclusion Criteria

1. For healthy donors:

a. Individuals who are unable or unwilling to donate blood samples b. Individuals with self-reported chronic metabolic diseases such as type 2 diabetes, impaired glucose tolerance or morbid obesity c. Individuals with self-reported acute infection (respiratory or others) or chronic infection (such as HIV,hepatitis B or -C) d. Individuals with self-reported immune-mediated diseases such as multiple sclerosis, type 1 diabetes, primary immunodeficiency e. Individuals with self-reported current or prior history of malignancy f. Individuals who are currently pregnant (self-report) g. Corticosteroid therapy equivalent to >/= 10 mg/day of prednisone within the last 4 weeks h. Immunosuppressive therapy at any time prior to enrollment (such as Cyclophosphamide, Mitoxantrone, Imuran, Cellcept, Methotrexate, Rituximab, Alemtuzumab)

2. For all subjects with an autoimmune disease:

a. Pregnant patients b. Pediatric patients unable to donate at least 51 mL of blood per NIH guidelines (no more than 5 mL/kg in a single day and no more than 9.5 mL/kg over any 8 week period) c. Patients with current substance abuse or alcoholism (self-report) d. Patients diagnosed with more than one autoimmune and/or inflammatory disease, exception - asthma is permissible e. Corticosteroid therapy equivalent to > 10 mg/day of prednisone within the last 4 weeks f. Immunomodulatory therapies within the last 12 months (such as Interferon, Glatiramer Acetate, Natalizumab, Fingolimod) g. Immunosuppressive medication at any time prior to enrollment (such as Cyclophosphamide, Mitoxantrone, Imuran, Cellcept, Methotrexate, Rituximab, Alemtuzumab) h. Any prior or current Anti-tumor necrosis factor (anti-TNF) treatments i. Any prior or current use of experimental drugs tested in Phase I, II, or III clinical trials

3. Diagnosis of ulcerative colitis or indeterminate colitis

4. Pustular psoriasis, isolated palmoplantar psoriasis, isolated inverse psoriasis and isolated sebopsoriasis.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Identify shared defects in T and B cell function by disease classification	One-time blood draw	The study aims to establish whether defects in T and B cell function are shared across multiple immune-mediated diseases and whether these are driven by shared genetic risk variants.

Trial Locations

Locations (6)

Yale University; 🇺🇸 New Haven, Connecticut, United States

Baylor Institute of Immunology Research - Clinical Rheumatology; 🇺🇸 Dallas, Texas, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Oklahoma Medical Research Foundation; 🇺🇸 Oklahoma City,, Oklahoma, United States

Feinstein Institute for Medical Research; 🇺🇸 Manhasset, New York, United States