Clinical trial NCT01990898: Cyclosporine in Interstitial Cystitis: Efficacy, Safety and Mechanism of Action
Official title: Cyclosporine in Interstitial Cystitis: Efficacy, Safety and Mechanism of Action
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Interstitial Cystitis
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2013-11-25
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Symptom Improvement of Interstitial Cystitis
timeFrame: 3 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic - Main Campus Only
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Daniel Shoskes, M.D.
role: PRINCIPAL_INVESTIGATOR
References: