Mycophenolate Mofetil to Treat Wegener’s Granulomatosis and Related Vascular Inflammatory Conditions

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Brief Title

Mycophenolate Mofetil to Treat Wegener's Granulomatosis and Related Vascular Inflammatory Conditions

Official Title

Mycophenolate Mofetil in the Treatment of Wegener's Granulomatosis and Related Vasculitides

Brief Summary

      This study will examine the safety and effectiveness of the drug mycophenolate mofetil (MPM)
      in treating Wegener's granulomatosis and related inflammatory vessel diseases. Blood vessel
      inflammation in these patients may involve different parts of the body, including the brain,
      nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and other
      sites. The more severe the involvement, the more likely the disease will be life-threatening.
      Standard treatment consists of combination drug therapy with prednisone and a cytotoxic
      agent-usually cyclophosphamide or methotrexate. However, some patients in whom this treatment
      is initially successful have a disease relapse; other patients cannot take the medications
      because of other health problems or because of severe side effects of the drugs.

      MPM is approved by the Food and Drug Administration to prevent kidney transplant rejection.
      It is chemically similar to another cytotoxic drug called azathioprine, which has been
      beneficial in maintaining remission in patients with Wegener's granulomatosis who have been
      treated successfully with cyclophosphamide. Because MPM is more effective than azathioprine
      in preventing organ rejection, it may also prove beneficial as a second-line treatment for
      Wegener's granulomatosis.

      Patients with Wegener's granulomatosis or related inflammatory vessel diseases who have had a
      relapse following treatment with cyclophosphamide and methotrexate or who cannot take one or
      both of these drugs may be eligible for this study. Only patients who have been treated at
      NIH in the methotrexate protocol or the cyclophosphamide switching to methotrexate protocol,
      or who have received the exact same treatment from their own physician may participate.

      Participants will have a complete medical evaluation including laboratory studies.
      Consultations, X-rays and biopsies of affected organs may also be done if indicated for
      diagnosis or treatment. Patients with active disease will be given MPM and prednisone, both
      in tablet form. Patients with inactive disease will receive only prednisone if they are
      already taking it. In both cases, the prednisone will be reduced gradually and discontinued
      if the disease improves significantly. MPM therapy will continue for at least 2 years. If
      after 2 years the disease remains in remission, the MPM dose will be gradually reduced and
      then stopped. If active disease recurs while on MPM therapy, the treatment plan will likely
      be changed. The new regimen will be determined by the severity of disease, other medical
      conditions, and history of side effects to previous medications.

      Patients will be followed at the NIH clinic every month for the first 3 months on MPM and
      then every 3 months for another 18 months. Those whose disease has remained in remission and
      have stopped all medications will then be followed every 6 months for 4 visits. The follow-up
      visits will include a physical examination, blood draws, and, if needed, X-rays. Visits may
      be scheduled more frequently if medically indicated.
    

Detailed Description

      The purpose of this study is to assess the efficacy and safety of mycophenolate mofetil in
      the treatment of Wegener's granulomatosis and related vasculitides in patients who have
      contraindications to methotrexate or cyclophosphamide or have experienced disease relapse
      while on these agents. Mycophenolate mofetil is a novel immunosuppressive agent which has
      been approved by the FDA for renal transplantation. It is chemically similar to and has a
      potentially greater efficacy in preventing acute transplant rejection than azathioprine, a
      drug which has been previously used as an alternative treatment for vasculitis. In this
      study, patients who have had disease relapse or contraindications to methotrexate will
      initially receive cyclophosphamide and glucocorticoids and then switch from cyclophosphamide
      to mycophenolate mofetil upon disease remission. If at the end of two years of mycophenolate
      mofetil therapy there is continued evidence of disease remission, the drug will be tapered
      and discontinued. Patients with contraindications to both cyclophosphamide and methotrexate
      will be treated initially with prednisone and mycophenolate mofetil with mycophenolate
      mofetil being continued for two full years after disease remission and then tapered and
      discontinued. For patients who develop intolerance to methotrexate or cyclophosphamide while
      their disease is in remission, mycophenolate mofetil will be started and continued for two
      years after which time it will be tapered and discontinued. Patients will be prospectively
      monitored for evidence of disease activity and drug toxicity. Specific parameters that will
      be obtained include the time to disease remission, the rate and time of disease relapse, and
      the incidence of drug related adverse effects.
    

Study Phase

Phase 1

Study Type

Interventional




Condition

Vasculitis

Intervention

Mycophenolate Mofetil


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

50

Start Date

April 1998

Completion Date

June 2004


Eligibility Criteria

        INCLUSION CRITERIA:

        Documentation of Wegener's Granulomatosis (WG) based on clinical characteristics and
        histopathological evidence of vasculitis.

        Patient with a positive C- or P-ANCA and glomerulonephritis as evidenced by the presence of
        red blood cell casts and proteinuria or renal biopsy showing necrotizing glomerulonephritis
        in the absence of positive immunofluorescence for immunoglobulin and complement will also
        be eligible.

        Patients must be of the ages of 18-80 years.

        Patients on the CYC to MTX protocol (#95-I-0091) who experience a relapse of disease while
        on MTX maintenance therapy. Relapse is defined by a Vasculitis Disease Activity Index of
        greater than or equal to 3. Patients from outside the NIH will also be eligible if they
        have been treated with a CYC to MTX regimen identical to that used in #95-I-0091 and
        experience a relapse of disease while on MTX maintenance therapy. If treatment for this
        relapse has already been commenced at the outside institution with daily CYC and
        glucocorticoid, patients will still be eligible if there is a history of a Vasculitis
        Disease Activity Index greater than or equal to 3 at the time of CYC and glucocorticoid
        initiation. Patients who experience a relapse of disease after MTX has been stopped or
        while tapering the MTX dose (following 2 years of maintenance therapy) will not be
        eligible.

        Patients with active disease who have a contraindication to MTX therapy will be eligible.
        Evidence of active disease as defined by a Vasculitis Disease Activity Index of greater
        than or equal to 3.

        Patients with inactive disease who have a contraindication to CYC and. Evidence of active
        disease as defined by a Vasculitis Disease Activity Index of greater than or equal to 3.

        Patients with inactive disease on MTX while on the CYC to MTX protocol (95-I-0091) or the
        MTX protocol (90-I-0086) who develop an contraindication necessitating discontinuation of
        MTX. Patients from outside the NIH will also be eligible if they similarly develop a
        contraindication to MTX while on treatment.

        Patients with inactive disease on the CYC protocol (#76-I-0041 or 76-I-0042) who develop a
        contraindication necessitating CYC discontinuation and also have a contraindication to
        receiving MTX. Patients from outside the NIH will also be eligible if they similarly
        develop a contraindication to CYC while on treatment and cannot receive MTX.

        Patients with inactive disease who are receiving treatment with CYC and prednisone in a
        manner similar to #76-I-0042 will be eligible if they have a contraindication to receiving
        MTX and have been in remission for less 3 months.

        EXCLUSION CRITERIA:

        Evidence of active infection which, in the judgment of the investigator, is of greater
        danger to the patient than the underlying vasculitis. In those instances in which infection
        cannot be ruled out by gram stain and culture of secretions or collections of fluid in
        involved organs, it may be necessary to obtain a biopsy of the affected tissue for
        microbiological and histopathological studies.

        Patients who are pregnant or who are nursing infants will not be eligible. Fertile women
        must have a negative pregnancy test within one week prior to study entry and must be using
        an effective means of birth control.

        Patients with active disease who are eligible for the CYC to MTX protocol (#95-I-0091) or
        the MTX protocol (#90-I-0086).

        Active peptic ulcer disease.

        Serological evidence of infection with human immunodeficiency virus. A serological
        determination will be performed within two weeks of beginning study participation.

        Inability to comply with study guidelines.

        Creatinine clearance less than 25ml/min.
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00001764

Organization ID

980092

Secondary IDs

98-I-0092


Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

, , 


Verification Date

June 2004