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

NCT ID: NCT01990898

Last Updated: 2017-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2016-04-30

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.

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.

Conditions

Interstitial Cystitis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cyclosporine

Drug: Cyclosporine, Pill form, dosage calculated upon patient study visit, frequency - twice daily, duration - 3 months.

Group Type: EXPERIMENTAL

Cyclosporine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Gengraf Cyclosporine

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Shoskes, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic - Main Campus Only

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

13-1271

Identifier Type: -

Identifier Source: org_study_id