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

• ClinicalTrials.gov Identifier: NCT01990898
• Recruitment Status: Completed
• First Posted: November 25, 2013
• Results First Posted: April 19, 2017
• Last Update Posted: April 19, 2017
• Sponsor: The Cleveland Clinic
• Information provided by (Responsible Party): The Cleveland Clinic

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Interstitial Cystitis	Drug: Cyclosporine	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cyclosporine in Interstitial Cystitis: Efficacy, Safety and Mechanism of Action
• Study Start Date: November 2013
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: April 2016

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Symptom Improvement of Interstitial Cystitis [ Time Frame: 3 Months ]
   Number of participants with > 30% Improved Interstitial Cystitis Symptoms Index (ICSI) which is measured on a scale from 0 - 19 where the higher numbers are worse. No additional analyses have been done.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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 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)

Contacts and Locations

Locations

United States, Ohio

Cleveland Clinic - Main Campus Only

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

The Cleveland Clinic

Investigators

• Principal Investigator: Daniel Shoskes, M.D.; The Cleveland Clinic

More Information

• Responsible Party: The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT01990898
• Other Study ID Numbers: 13-1271
• First Posted: November 25, 2013
• Results First Posted: April 19, 2017
• Last Update Posted: April 19, 2017
• Last Verified: October 2016

Additional relevant MeSH terms:

Cystitis; Cystitis, Interstitial; Urinary Bladder Diseases; Urologic Diseases; Cyclosporine; Cyclosporins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors