Clinical trial NCT01947036: T and B Cell Responses in Autoimmune Diseases
Official title: T and B Cell Responses Across Autoimmune Diseases
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Type 1 Diabetes Mellitus
Multiple Sclerosis
Arthritis, Rheumatoid
Crohn's Disease
Psoriasis
Keywords: autoimmune disease
immune-mediated disease
T and B cells immunophenotype
IL23 signaling
genetic risk variants
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Autoimmunity Centers of Excellence
First posted: 2013-09-20
Enrollment: 68
Sex: ALL
Minimum age (years): 8
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants who are healthy or have a confirmed or suspected diagnosis of type 1 diabetes (T1D, T1DM), multiple sclerosis (MS), psoriasis (Ps), Crohn's disease (CD), or rheumatoid arthritis (RA) will be invited to donate a blood sample. No follow-ups are planned.

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.

Eligibility criteria: 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:
  1. Psoriasis diagnosis by a dermatologist
  2. Disease duration within 1 year
  3. 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.

Primary outcomes:
measure: Identify shared defects in T and B cell function by disease classification
timeFrame: One-time blood draw
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Manhasset
country: United States
facility: Feinstein Institute for Medical Research
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Oklahoma City,
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Dallas
country: United States
facility: Baylor Institute of Immunology Research - Clinical Rheumatology
state: Texas
Study officials:
affiliation: Yale University
name: Chris Cotsapas, PhD
role: PRINCIPAL_INVESTIGATOR
References: