Cyclosporine in Interstitial Cystitis: Efficacy, Safety and Mechanism of Action (CIC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by The Cleveland Clinic
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT01990898
First received: November 18, 2013
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Interstitial Cystitis
Drug: Cyclosporine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cyclosporine in Interstitial Cystitis: Efficacy, Safety and Mechanism of Action

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • To measure the effects of cyclosporine treatment on current perception and pain threshold using a Neurometer before, during and after treatment [ Time Frame: 3 Months ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: November 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cyclosporine
Drug: Cyclosporine, Pill form, dosage calculated upon patient study visit, frequency - twice daily, duration - 3 months.
Drug: Cyclosporine
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.
Other Name: Gengraf Cyclosporine

Detailed Description:

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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. chronic use of opiod therapy
  9. current or previous urinary diversion or bladder augmentation
  10. chronic use of a medication class with significant impact on CyA blood levels (eg. macrolide antibiotics, phenytoin, oral antifungals, calcium channel blockers)
  11. untreated urinary tract infection
  12. pregnant or breast feeding
  13. neurological impairment or spinal cord injury
  14. known hypersensitiviy to CyA
  15. concurrent use of another immunosuppressive drug (eg. oral corticosteroids, tacrolimus, mycophenolate mofetil)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01990898

Contacts
Contact: Daniel Shoskes, M.D. 216-445-4757 shosked@ccf.org

Locations
United States, Ohio
Cleveland Clinic - Main Campus Only Recruiting
Cleveland, Ohio, United States, 44195
Contact: Daniel Shoskes, M.D.    216-445-4757    shosked@ccf.org   
Principal Investigator: Daniel Shoskes, M.D.         
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Principal Investigator: Daniel Shoskes, M.D. The Cleveland Clinic
  More Information

No publications provided

Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01990898     History of Changes
Other Study ID Numbers: 13-1271
Study First Received: November 18, 2013
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cystitis, Interstitial
Cystitis
Urinary Bladder Diseases
Urologic Diseases
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 24, 2014