A Randomized Multicenter Double-Blind CT to Evaluate the Efficacy and Safety of Mycophenolate Mofetil . . . (ICCRN RCT2)

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Description

Brief Summary:

The purpose of this study is to investigate the safety and effectiveness of a medication called CellCept in treating refractory (has not responded to other treatments) interstitial cystitis.

CellCept belongs to a class of medications called immuno-suppressants. Immuno-suppressants work in the body by reducing the immune system's ability to produce certain reactions that can cause inflammation. In some people, the inflammation produced by their immune system can damage healthy tissues and cause symptoms of pain and discomfort. CellCept is approved by the U.S. Food and Drug Administration (FDA) for use in patients who have had an organ transplant. When used in combination with other drugs, CellCept helps to prevent the rejection of the transplanted organ and is used widely in patients who have received kidney, liver and heart transplants. CellCept is also frequently used but not FDA approved for the treatment of severe rheumatoid arthritis which is a disease caused when the body's immune system acts against healthy tissues in the joints.

Due to its special activity, CellCept may be useful in treating certain inflammatory diseases or conditions like interstitial cystitis.

Condition or disease	Intervention/treatment	Phase
Interstitial Cystitis; Painful Bladder Syndrome	Drug: Mycophenolate Mofetil; Drug: Mycofenolate Mofetil (MMF); Drug: Placebo	Phase 3

Detailed Description:

Interstitial Cystitis (IC) is a bladder syndrome characterized as painful, debilitating and chronic, with no universally successful treatment option currently available. Characteristic symptoms include pain with bladder filling, and marked urinary frequency (to relieve pain). The only FDA-approved oral medication for treatment of IC is pentosan polysulfate (Elmiron), recently demonstrated by our collaborative research network to perform with little more efficacy than placebo (ref), and which is expensive and has associated side effects. Current clinical treatment protocols are empiric and usually aimed at relieving pain. There is a pressing need for an effective oral medication for treatment of IC. The presentation of symptoms can be quite variable among patients, suggesting that IC is a multi-factorial syndrome with several proposed etiologies, some of which may be interrelated.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Multicenter Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Mycophenolate Mofetil (CellCept) for the Treatment of Refractory Interstitial Cystitis (IC)
• Study Start Date: March 2007
• Actual Primary Completion Date: February 2008
• Estimated Study Completion Date: April 2008

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: A; 2000 mg per day of CellCept (MMF) divided into 2 equal doses.	Drug: Mycophenolate Mofetil; Other Name: CellCept; Drug: Mycofenolate Mofetil (MMF); 2000 mg per day divided into 2 equal doses.; Other Name: CellCept
Placebo Comparator: B; Placebo	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. To compare CellCept 2 grams daily to placebo for effects on overall IC symptoms and well being in patients with refractory PBS/IC. [ Time Frame: 12 Weeks ]
2. To assess the safety profile of CellCept in the treatment of refractory PBS/IC. [ Time Frame: 12 Weeks ]

Secondary Outcome Measures :

1. To investigate the association between clinical subgroups, characterized by differences in baseline characteristics (such as presence of ulcers, duration of symptoms, significant co-morbid diseases, serological abnormalities), and efficacy of CellCept. [ Time Frame: 12 Weeks ]
2. To assess the patterns of patient expectations, associations with symptom severity, and the potential impact of patient expectations on response to treatment. [ Time Frame: 12 Weeks ]
3. To assess patterns of treatment goals and goal achievement in this study population, as well as baseline characteristics and factors related to goal selection and achievement. [ Time Frame: 12 Weeks ]
4. To assess impact of study medication on pain medication use. [ Time Frame: 12 Weeks ]
5. To assess the frequency and mechanism of un-blinding on study results and assess how the patient's perception of which treatment they received changes over time and influences ultimate outcome. [ Time Frame: 12 Weeks ]
6. To assess the rate of detectable immune disorders in patients with PBS/IC refractory to standard treatment using CellCept. [ Time Frame: 12 Weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Participant at least 18 years of age and received a diagnosis of PBS/IC, confirmed by cystoscopy and hydrodistention in the past with findings of glomerulations and/or ulceration.
• Participant has symptoms of urinary frequency and pain/discomfort (at least 4 on each 0-10 Likert scale) at entry.
• Participant failed at least 24 weeks of active treatment with a minimum of 3 standard forms of therapy (including hydrodistension) or combination of therapies for PBS/IC.
• Participant will receive cystoscopy to be performed in the office at baseline visit before randomization if none has been conducted within the previous 24 weeks. Cystoscopy results must show no unevaluated lesions.
• Female participants with a cervix are required to have Pap smear exam within the past 12 months prior to enrollment with normal results reported.
• Participant (female) with child-bearing potential must agree to use two reliable/medically approved methods of birth control.

Exclusion Criteria:

• History of cancer or known pre-malignant conditions, including skin cancer.
• History of bladder calculus, tuberculous cystitis; neurologic disease affecting bladder function.
• Current immunocompromised condition, including current or chronic treatment with immunosuppressive agents, or known positive for HIV (positive antibody confirmed by Western Blot or IFA); active tuberculosis requiring on-going therapy; current systemic steroid treatment at any dose.
• Liver function test or creatinine results greater than 2x the upper limit of normal at home institution laboratory.
• Any baseline leukopenia (an absolute neutrophil count <1,500/µL), thrombocytopenia (a platelet count less than 150,000/microL), or anemia - HGB < 12 or < 11 g/dLin men and in women respectively.
• Is seropositive for Hepatitis B surface antigen; or is seropositive for Hepatitis B surface antibody (if not previously vaccinated); is seropositive for Hepatitis C antibody or HIV antigen or antibody.
• Allergy or hypersensitivity to study medication.
• Unable to void spontaneously.
• Active urethral or ureteral calculi, urethral diverticulum.
• Any severe debilitating or urgent concurrent medical condition.
• Previous cytoxan/cyclophosphamide treatment, pelvic radiation therapy; augmentation cystoplasty, cystectomy, or cystolysis; neurectomy.
• Participants with history of treatment for genital tract dysplasia or genital warts or genital herpes.
• Patients with active or a history of peptic ulcer disease, inflammatory bowel disease or gastrointestinal bleeding.
• Patients with hypertension not adequately controlled with medication.
• Patient currently taking H2 blockers or proton pump inhibitors.
• Patients who cannot tolerate or refuse an office cystoscopy.

Exclusion criteria for men only:

• Currently being treated for chronic bacterial prostatitis, as documented by a positive urine culture or prior history of recurrent bacterial urinary infections.
• Unevaluated suspicious prostate exam.

Exclusion criteria for women only:

• Lactation, pregnancy, or refusal of two types of (medically approved/reliable) birth control in women of child-bearing potential.
• Pain, frequency, urgency symptoms present only during menses.

Contacts and Locations

Locations

United States, California

Univeristy of California San Diego

San Diego, California, United States, 92093

Stanford University Medical center

Stanford, California, United States, 94305

United States, Illinois

Loyola University Medical Center

Maywood, Illinois, United States, 60153

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States, 48202

William Beaumont Hospital

Royal Oak, Michigan, United States, 48073

United States, New York

University of Rochester

Rochester, New York, United States, 14642

United States, Pennsylvania

University of Pennsylvania Health System

Philadelphia, Pennsylvania, United States, 19104

United States, Washington

University of Washington

Seattle, Washington, United States, 98195

Canada, Ontario

Queen's University

Kingston, Ontario, Canada, K7L2V7

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Study Director: John Kusek, PhD; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Study Director: LeRoy Nyberg, MD, PhD; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Principal Investigator: Richard Landis, PhD; University of Pennsylnania
• Study Chair: David Burks, MD; Henry Ford Hospital
• Principal Investigator: Harris Foster, MD; Yale University

More Information

Additional Information:

Interstitial Cystitis Association 

• Responsible Party: LeRoy M. Nyberg, PhD., MD, NIDDK
• ClinicalTrials.gov Identifier: NCT00451867 History of Changes
• Other Study ID Numbers: DK765209-Cellcept (IND)
• First Posted: March 26, 2007
• Last Update Posted: January 14, 2010
• Last Verified: January 2010

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

interstitial cystitis research; painful bladder syndrome research; pelvic pain research; interstitial cystitis and autoimmune; interstitial cystitis and cellcept; interstitial cystitis and mycophenolate mofetil; interstitial cystitis and MMF; interstitial cystitis and inflammation; inflammatory diseases and immunosupression

Additional relevant MeSH terms:

Mycophenolic Acid; Cystitis; Cystitis, Interstitial; Urinary Bladder Diseases; Urologic Diseases; Antibiotics, Antineoplastic; Antineoplastic Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action