Retinoids in ANCA Small Vessel Vasculitis: Silencing Autoantigens
Retinoids in ANCA Small Vessel Vasculitis: Silencing Autoantigens
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.
Inclusion Criteria:

 -  Patients with ANCA disease and no more than mild activity as determined by a BVAS
 score of 1 to 4. These are patients who will have undergone induction with
 cyclophosphamide and corticosteroids in the past, and will be in partial remission on
 maintenance therapy with azathioprine or mycophenolate mofetil with or without small
 dose prednisone. We anticipated that most patients enrolled in the study will have low
 grade persistent ("grumbling") disease on stable immunosuppressants.

 -  Documented 6-fold or greater elevation in PR3 and/or MPO gene expression by the RT-PCR
 technique. We estimate that approximately 25% of patients with a BVAS <5 will have an
 elevation in PR3 and/or MPO gene expression based on our previous studies. 2 Patients
 must be on stable maintenance therapy with prednisone (<10 mg/day or equivalent),
 cyclosporine A, mycophenolate mofetil or azathioprine for at least 8 weeks.

 Exclusion Criteria:

 -  Patients with severe, active vasculitis requiring institution or an increase in dose
 of corticosteroids, cyclophosphamide, azathioprine, mycophenolate mofetil or any new
 immunosuppressive medication within the previous 8 weeks or at the time of enrollment.

 -  Pregnancy, breastfeeding, or unwillingness to use at least two contraceptive methods
 (at least one of which must be primary, including tubal ligation, partner vasectomy,
 oral contraceptives, implanted contraceptives, and intrauterine device). The rationale
 is that retinoids are teratogenic and are excreted in breast milk. Contraceptive
 methods must be instituted at least 1 month before starting tretinoin and continued at
 least 1 month after stopping the medication.

 -  History of hepatitis, cirrhosis or abnormal liver tests, including aspartate
 aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase,
 Gamma-glutamyl transpeptidase (GGT), total bilirubin, or prothrombin time; unless the
 abnormality is due to a specific hepatotoxic medication, AND the liver test levels are
 l< 2 times the upper limit of the normal AND normalize upon holding the offending
 drug.

 -  Hypertriglyceridemia (>500 mg/dL) despite statin/fibrate therapy.

 -  Any medical conditions requiring concurrent use of tetracycline, minocycline, or
 doxycycline, due to enhanced risk of increased intracranial pressure.

 -  Any medical conditions requiring concurrent use of rifampin, phenobarbital,
 pentobarbital, ketoconazole, cimetidine, erythromycin, verapamil, diltiazem, vitamin A
 and antithrombotic agents (Tranexamic Acid, Aminocaproic Acid or Aprotinin)due to the
 potential for interactions with tretinoin therapy.

 -  Presence of unstable cardiovascular disease, uncontrolled diabetes with hemoglobin A1c
 > 8% g/dL, or chronic inflammatory or infectious conditions.

 -  Glomerular Filtration Rate (GFR) <25 ml/min/1.73m^2 as estimated by the MDRD equation,
 as the metabolites of retinoids are excreted in part in urine, and there is a concern
 for increased toxicity.

 -  Untreated depression, as retinoids have been associated with depression, suicidal
 ideation, and aggressive behavior.

 -  Neutropenia (neutrophil count < 1000 cell/mm^3).

 -  Known osteoporosis.