Cyclosporine in Interstitial Cystitis: Efficacy, Safety and Mechanism of Action
Condition: Interstitial Cystitis
MeSH terms: Cystitis; Cystitis, Interstitial
Intervention: Cyclosporine
Intervention description: Drug will be provided to patient's at study visit. Drug is to be taken twice daily. Dosage will be calculated at study visit and provided to patient.
Intervention MeSH terms: Cyclosporine; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This is a study for patients that have a condition called Interstitial Cystitis, also known
      as Painful Bladder Syndrome. Patients would have tried at least two different therapies,
      unsuccessfully,(eg. medications, pelvic floor physical therapy)

      The purpose of this research project is to study the immunosuppressive drug Cyclosporine in
      patients with Interstitial Cystitis to assess how well it works, what the side effects are
      and what is its mechanism of action. Cyclosporine is a drug that is FDA-approved to prevent
      organ rejection after kidney, liver, and heart transplant but is not approved by the FDA for
      Interstitial Cystitis. Several research studies have been published showing that Cyclosporine
      can improve the symptoms of Interstitial Cystitis, that it works better than a placebo
      ("sugar pill" or inert treatment) and that it works more effectively than Pentosan
      Polysulfate (Elmiron), which is an FDA approved therapy. The dose of Cyclosporine used in
      these studies on Interstitial Cystitis are much lower that the doses used to prevent
      rejection in transplant patients.

      Based on these studies, the American Urological Association has recently published treatment
      guidelines that recommend Cyclosporine therapy for Interstitial Cystitis after the failure of
      other more conservative therapies and medications. Nevertheless, much is not known about
      using Cyclosporine therapy for Interstitial Cystitis including the mechanism of action, the
      ideal dose, how best to monitor for side effects and in particular whether kidney damage can
      occur at the low doses used in these studies. In this study, to examine the mechanism of
      action, blood and urine samples will be collected before, during and after therapy to look at
      "biomarkers", chemical substances that can be associated with inflammation and tissue injury.
      We will also test effects of therapy on skin sensation and pain perception because the
      molecule which Cyclosporine binds to (calcineurin) is also found in nerves that conduct pain
      signals.

      This study is only being done at the Cleveland Clinic and will involve about 30 patients with
      Interstitial Cystitis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. age > 18

          2. able to give consent

          3. commitment to return for follow up appointments

          4. agree to all parts of the study, including pain sensation testing

          5. total Interstitial Cystitis Symptom Index (ICSI) score >9

        Exclusion Criteria:

          1. active cancer

          2. history of pelvic radiation

          3. history of previous urological malignancy

          4. serum Cr > 1.5 mg/dl

          5. diagnosis of diabetes mellitus types I or II

          6. untreated hypertension or blood pressure on treatment > 140/90

          7. proteinuria at enrollment

          8. current or previous urinary diversion or bladder augmentation

          9. chronic use of a medication class with significant impact on Cyclosporine A (CyA)
             blood levels (eg. macrolide antibiotics, phenytoin, oral antifungals, calcium channel
             blockers)

         10. untreated urinary tract infection

         11. pregnant or breast feeding

         12. neurological impairment or spinal cord injury

         13. known hypersensitivity to CyA

         14. concurrent use of another immunosuppressive drug (eg. oral corticosteroids,
             tacrolimus, mycophenolate mofetil)