The purpose of this research study is to learn if adding all-trans retinoic acid (tretinoin) to conventional treatment of Anti- Neutrophil Cytoplasmic Autoantibodies (ANCA) vasculitis can decrease the level of disease activity.
Neutrophils are white blood cells that are the target of the ANCA antibodies. T cells are white blood cells that are involved in regulating the immune system. Laboratory research studies suggest that all-trans retinoic acid (tretinoin) can affect the neutrophils and the T lymphocytes in such a way that could decrease the abnormal immune response directed against the body own neutrophils.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Patients will be started at half the recommended dose of retinoic acid for the treatment of acute promyelocytic leukemia (APL), i.e. 22.5mg/m2/day orally in two divided doses, to minimize the risk of adverse events. If there is no decrease in PR3/MPO gene expression to a fold change of \< 2 by quantitative polymerase chain reaction(QT-PCR) technique for PR3 at the end of 4 weeks, the dose will be increased to 45 mg/m2/day in two divided doses for an additional 8 weeks. If the patient shows a decrease in PR3/MPO gene expression to \< 2 at 4 weeks, the patient will remain on the same dose for the remainder of 12 weeks. All patients will be followed for a total of 12 months for safety evaluations and to assess changes in disease activity and the incidence of disease relapse.
maintenance therapy with azathioprine or mycophenolate mofetil with or without small dose prednisone. Dose, frequency and duration depend on disease activity (partial or complete remission).
UNC Kidney Center
Chapel Hill, North Carolina, United States
change in leukocyte Myeloperoxidase (MPO) and Proteinase 3 (PR3) message
normalization of PR3 and MPO message at the end of treatment.
Time frame: week 12
Birmingham Vasculitis Activity Score (BVAS)
(1) Change in BVAS at the end of treatment (week 12) and at week 52, compared to baseline (day 1); (2) Change in Treg and Th17 cells at weeks 12 and 52, compared to baseline (day 1); and (3) the frequency of relapse during the follow up period.
Time frame: 52 weeks
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