Budesonide for Liver Transplant Immune Suppression
Condition: Acute Cellular Graft Rejection; New Onset Diabetes After Transplant
Intervention: Budesonide 3Mg Capsule; Standard of Care Prednisone
Intervention description: Budesonide capsule in place of prednisone (standard of care); Prednisone taper (Standard of Care)
Intervention MeSH terms: Prednisone; Budesonide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: 20 subjects will receive open label Budesonide along with standard immune suppression and their outcomes will be compared to 20 matched controls receiving standard of care treatment including prednisone plus standard immune suppression
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 21 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is a pilot study that investigates the efficacy and safety of budesonide as an immune
      suppressing agent for liver transplant recipients in the early post-transplant period.

      The primary end-point is rates of acute cellular rejection within first 24 weeks post-liver
      transplant. Secondary end points include rates of new onset diabetes after transplant and
      safety of budesonide.

      The study is structured as a prospective clinical trial. After receiving 4 days of
      intravenous corticosteroids on liver transplant post-operative days 0 through 3, subjects
      will be started on standard immunosuppression plus enteric coated budesonide (study drug) in
      place of standard immune suppression plus prednisone (standard of care). Study drug will be
      tapered over 12 weeks in accordance with the existing standard of care immune suppression
      protocol. Subjects will be followed in outpatient transplant clinic for 24 weeks. The purpose
      of the study is to conduct a pilot study to generate rates and effect size that can be used
      in a subsequent equivalent trial. A total of 20 subjects will be enrolled to receive the
      standard immunosuppression plus budesonide and their outcomes will be compared to 20 controls
      receiving standard immunosuppression plus prednisone (standard of care). The use of controls
      is to generate rate and variability that can be compared with the rate obtained from patients
      that receive study drug by examining the 95% confidence band.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female or male subjects aged 21-75 years old

          -  Received a primary liver transplant within 4 days of enrollment

        Exclusion Criteria:

          -  Received previous organ transplants

          -  Undergoing multiple organ transplants

          -  Recipients with advanced fibrosis in graft

          -  Treatment plan for subject includes receiving immunosuppressant therapy other than
             standard immune suppression (SIS) as per University of Cincinnati LT immune
             suppression protocol (UC-ISP).

          -  Inability to take enteral (orally or by tube feed) medications by day 4
             post-transplant

          -  Subjects with diabetes mellitus prior to transplant (diabetes mellitus defined as use
             of hypoglycemic agents or HbA1c > 6.4 prior to transplant)

          -  Subjects who have any severe medical condition requiring acute or chronic treatment
             that in the investigator's opinion would interfere with study participation.

          -  Subjects who have been exposed to an investigational therapy within 30 days prior to
             enrollment or 5 half-lives on the investigational product, whichever is greater.

          -  Subjects in which concomitant use of medications which are inhibitors of CYP3A4 (such
             as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin) cannot
             be avoided during the study period.

          -  Pregnant females

          -  Diminished mental capacity to consent for the study as determined by attending on the
             record.