A Randomized Multicenter Double-Blind CT to Evaluate the Efficacy and Safety of Mycophenolate Mofetil . . . - Full Text View

Sponsored by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00451867

Purpose

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	Intervention	Phase
Interstitial Cystitis Painful Bladder Syndrome	Drug: Mycophenolate Mofetil Drug: Mycofenolate Mofetil (MMF) Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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)

Resource links provided by NLM:

MedlinePlus related topics: Interstitial Cystitis

Drug Information available for: Mycophenolate mofetil hydrochloride Mycophenolate Mofetil

U.S. FDA Resources

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
To assess the safety profile of CellCept in the treatment of refractory PBS/IC. [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
To assess impact of study medication on pain medication use. [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
To assess the rate of detectable immune disorders in patients with PBS/IC refractory to standard treatment using CellCept. [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]

Enrollment:	210
Study Start Date:	March 2007
Estimated Study Completion Date:	April 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator 2000 mg per day of CellCept (MMF) divided into 2 equal doses.	Drug: Mycophenolate Mofetil Drug: Mycofenolate Mofetil (MMF) 2000 mg per day divided into 2 equal doses.
B: Placebo Comparator Placebo	Drug: Placebo Placebo

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00451867

Locations

United States, California
Stanford University Medical center
Stanford, California, United States, 94305
Univeristy of California San Diego
San Diego, California, United States, 92093
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
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
Henry Ford Hospital
Detroit, Michigan, United States, 48202
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 This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	NIDDK ( LeRoy M. Nyberg, PhD., MD )
Study ID Numbers:	DK765209-Cellcept
Study First Received:	March 23, 2007
Last Updated:	June 25, 2008
ClinicalTrials.gov Identifier:	NCT00451867 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board; Canada: Health Canada

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

Study placed in the following topic categories:

Cystocele
Immunologic Factors
Urinary Bladder Diseases
Mycophenolic Acid
Cystitis
Pain
Immunosuppressive Agents

Inflammation
Anti-Bacterial Agents
Cystitis, Interstitial
Pelvic Pain
Urologic Diseases
Mycophenolate mofetil

Additional relevant MeSH terms:

Disease
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Urinary Bladder Diseases
Physiological Effects of Drugs
Mycophenolic Acid
Cystitis
Enzyme Inhibitors

Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions
Cystitis, Interstitial
Pathologic Processes
Urologic Diseases
Therapeutic Uses
Syndrome
Mycophenolate mofetil

ClinicalTrials.gov processed this record on July 02, 2009