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Defining Immune Tolerance in ANCA-associated Vasculitis (AAV)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01934504
First received: August 29, 2013
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

The goal of the study is to find biological markers (certain proteins or cellular markers found in a blood test) that will inform doctors which AAV patients are most likely to be able to stop their medications suppressing their immune systems and remain in remission.


Condition
ANCA-associated Vasculitis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Tolerance Biomarker Identification [ Time Frame: Difference from baseline to week 26 ] [ Designated as safety issue: No ]
    Identification of biomarkers associated with clinical tolerance in patients with ANCA-associated vasculitis by comparative immunophenotyping of individual leukocyte subsets from tolerant and non-tolerant patients with AAV.


Secondary Outcome Measures:
  • Tolerance Signature Stability [ Time Frame: Baseline to Week 26 ] [ Designated as safety issue: No ]
    Measurement of the stability of a tolerance immune signature in patients with AAV over time.

  • Tolerance Signature vs. Clinical Status [ Time Frame: Baseline to Week 26 ] [ Designated as safety issue: No ]
    Correlation of possible changes in the tolerance signature with changes in clinical status.

  • Immunosuppression Associated Signature [ Time Frame: Baseline to 8 Weeks Post-Immunosuppression Withdrawal ] [ Designated as safety issue: No ]
    Definition of an immune signature associated with maintenance immunosuppression.


Estimated Enrollment: 105
Study Start Date: December 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Non-Tolerant
Non-Tolerant participants with AAV
Healthy Control Participants
Tolerant
Tolerant participants with AAV

Detailed Description:

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are small vessel vasculitides that typically follow a chronic course and are associated with death and serious illness. Three clinical conditions are recognized: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (Wegener's, GPA) and eosinophilic granulomatosis with polyangiitis (EPA, formerly Churg Strauss Syndrome). These have different clinical features but can have some overlapping immunological characteristics.

The precise cause of AAV is not understood, but there are clear genetic associations which, in the context of predisposing environmental factors, such as infections, may lead to development of disease. There are no diagnostic criteria for AAV, but there are validated classification criteria and disease definitions. There is a need to find biological markers that define immunological tolerance so that immunotherapy medicines may be correctly changed and safely withdrawn in some people.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Non-tolerant: Patients who have persistently active disease. Tolerant: Those patients who have become ANCA negative, having been ANCA positive at the time of their acute presentation but have been in prolonged disease- free remission off all immunotherapy for at least two years.

Criteria

Inclusion Criteria:

Tolerant AAV participants

  • Age 18 years or older.
  • Diagnosis of granulomatosis with polyangiitis (Wegener's, GPA) or microscopic polyangiitis, MPA according to the definitions of the CHCC.
  • History of being MPO-ANCA positive during a disease flare.
  • In clinical remission with BVAS/WG = 0 and off all immunosuppression for ≥ 2 years.
  • Negative MPO-ANCA and PR3-ANCA by ELISA at screening.
  • For women of child-bearing potential, a negative urine or serum pregnancy test at the time of screening.
  • Ability to sign and understand informed consent.
  • Willingness to comply with study procedures.

Non-Tolerant AAV participants

  • Age 18 years or older.
  • Diagnosis of granulomatosis with polyangiitis (Wegener's), GPA or microscopic polyangiitis, MPA according to the definitions of the CHCC.
  • History of being MPO-ANCA positive during a disease flare.
  • Within the past 5 years must have had a disease exacerbation, defined as an increase in the BVAS/WG score and re-institution of immunosuppressive therapy after therapy had been reduced or completely discontinued.
  • In clinical remission with BVAS/WG = 0 and on minimal maintenance therapy for ≥ 3 months prior to the screening visit. Minimal maintenance therapy is defined as:

    • Low-dose glucocorticoids (≤ 10 mg of prednisone or prednisilone daily) and/or:

      • Azathioprine≤150mgdailyor
      • Mycophenolate mofetil ≤ 1 gram daily or mycophenolate sodium ≤ 720 mg daily.
  • Positive MPO-ANCA by ELISA on at least 2 occasions within the last 52 weeks, the most recent result being within 8 weeks of visit -1.
  • For women of child-bearing potential, a negative urine or serum pregnancy test at the time of screening.
  • Ability to sign and understand informed consent.
  • Willingness to comply with study procedures.

Healthy Controls

  • Healthy participant age 18 years or older.
  • For women of child-bearing potential, a negative urine or serum pregnancy test at the time of screening.
  • Ability to sign and understand informed consent.
  • Willingness to comply with study procedures.

Exclusion Criteria:

Tolerant AAV Participants

  • Use of systemic IV or oral glucocorticoids for ˃ 1 month for any non-vasculitis indication within 8 weeks of the screening visit.
  • Any prior treatment with rituximab.
  • Presence of known chronic viral infections or autoimmune diseases.
  • History of malignancy, excluding non-melanomatous skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit.

Non-Tolerant AAV participants

  • Use of IV pulse glucocorticoids (methylprednisolone or other) or cyclophosphamide within the year prior to the screening visit.
  • Use of IV or oral glucocorticoids for > 1 month for any non- vasculitis indication within 8 weeks of screening visit.
  • Any prior treatment with rituximab.
  • Maintenance therapy with methotrexate within 3 months of the screening visit.
  • Presence of known chronic viral infections or other autoimmune diseases.
  • History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit.

Healthy Controls

  • Use of IV or oral glucocorticoids for > 1 month for any non-vasculitis indication within 8 weeks of the screening visit.
  • Presence of known chronic viral infections or other autoimmune diseases.
  • History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit.

AAV Participants Discontinuing Immunosuppression

  • Any prior treatment with rituximab.
  • Maintenance therapy with methotrexate within 3 months of the screening visit.
  • Presence of known chronic viral infections or other autoimmune diseases.
  • History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ, within 5 years of the screening visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01934504

Contacts
Contact: Alan Salama, MD a.salama@.ucl.ac.uk

Locations
United Kingdom
School of Immunity and Infection, Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham Not yet recruiting
Birmingham, England, United Kingdom
Principal Investigator: Lorraine Harper, MD         
Addenbrooke's Hospital Recruiting
Cambridge, England, United Kingdom, CB2 0QQ
Principal Investigator: David Jayne, MD         
Hammersmith Hospital Recruiting
London, England, United Kingdom, W12 0HS
Principal Investigator: Charles Pusey, MD         
University College London, Centre for Nephrology Recruiting
London, England, United Kingdom, NW32PF
Contact: Cindy Bhagwandin    44 2077940500 ext 34914    c.bhagwandin@ucl.ac.uk   
Principal Investigator: Alan Salama, MD         
Sponsors and Collaborators
Investigators
Study Chair: Alan Salama, MD University College London, Centre for Nephrology
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01934504     History of Changes
Other Study ID Numbers: DAIT ITN051AI, AVATARS
Study First Received: August 29, 2013
Last Updated: February 6, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vascular Diseases
Cardiovascular Diseases
Systemic Vasculitis
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 28, 2014