The first in a series of treatment studies planned by the IC Clinical Trials Group tested the effectiveness of pentosan polysulfate sodium (Elmiron®) and hydroxyzine hydrochloride (Atarax®) in 121 patients with IC. Most volunteers reported experiencing moderate pain, discomfort, and urinary frequency for at least a year before entering the study.
IC is a chronic, debilitating condition that affects about a million people, most of them women. Patients suffer pelvic, bladder, or perineal pain and the urge to urinate as often as 18 times a day. Available treatments are limited and not effective for everyone. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) initiated the Clinical Trials Group in 1998 to identify useful therapies for this devitalizing and difficult disease with no known cause and no cure. The Group is also supported by the NIH Office of Research on Women's > Health.
Elmiron® and Atarax® were chosen for early testing because patients prefer oral drugs and each drug has different mechanisms of action. Elmiron® is the only oral drug approved by the Food and Drug Administration for IC. Doctors do not know exactly how it works, but one theory is that it may repair defects in the lining of the bladder. In some patients, mast cells are present in the tissue of the bladder wall, possibly a sign of an allergic or autoimmune reaction. Atarax®, an antihistamine previously untested in a randomized, placebo-controlled trial for IC, reduces mast cell activity. Mast cell activity can cause bladder inflammation and pain and may play a part in IC.
Patients in the randomized trial received either Elmiron® or Atarax®, a combination of the two, or a placebo. Researchers hoped that a combination treatment might result in faster, more effective symptom relief. However, neither of the drugs nor the combination therapy produced a statistically significant benefit in patients. Forty percent of volunteers who took the combined treatment benefited. Elmiron® alone helped 28 percent of patients in the trial, while 23 percent had a positive response to Atarax®. Side effects were minimal.
"We believe that IC may be caused by many different factors," says Leroy M. Nyberg, M.D., NIDDK's Urology Program Director. "That would explain why some treatments work for certain patients but not others. It's also possible that these treatments might work better for IC patients with less severe symptoms than those seen in the volunteers," Nyberg adds.
Because these treatments proved ineffective for the majority of patients, researchers do not plan to expand the trial, ordinarily the next step if a pilot study is successful. They say, however, that they have gained useful information for future clinical trials in IC. In fact, the group has already recruited patients for its second treatment study, which is testing whether the bacterium Bacillus Calmette-Guérin (BCG), directly instilled in the bladder, relieves the pelvic pain and frequent urination that are hallmarks of IC (see http://www.niddk.nih.gov/welcome/releases/10-25-01.htm).
For a fact sheet on IC, see http://kidney.niddk.nih.gov/kudiseases/pubs/interstitialcystitis/index.htm#2
A list of IC Clinical Trials Group centers and doctors follows, or see http://www.niddk.nih.gov/patient/ic.htm.
Interstitial Cystitis Clinical Trials Group
CALIFORNIA, Stanford
Stanford University Medical Center
Christopher K. Payne, M.D.
Kathryn Azevedo, Ph.D.
Gilbert Rigaud, M.D.
Debra Clay, R.N., B.S.N.
650-724-1753
CANADA, Kingston, Ontario
Queen's University
Alvaro Morales, M.D.
J. Curtis Nickel, M.D.
Joe Downey, B.Sc., M.Sc.
Laurel Emerson, R.N.
613-548-6033
MARYLAND, Baltimore
University of Maryland
Toby Chai, M.D.
Susan Keay, M.D.
Richard Marvel, M.D.
John Warren, M.D.
Linda Horne
Theresa Jackson
410-706-7560
MASSACHUSETTS, Boston
New England Medical Center
Erol Onel, M.D.
Grannum R. Sant, M.D.
T.C. Theoharides, Ph.D., M.D.
Patricia Radgowski
Carolyn Shea-O'Malley, R.N.
617-636-6317
MICHIGAN, Detroit
Henry Ford Hospital
David Burks, M.D.
Rifaat Dagher, M.D.
Michelle Peabody, R.N.
Jill Sullivan, R.N., B.S.N.
313-916-8972
MICHIGAN, Royal Oak
William Beaumont Hospital
Ananias C. Diokno, M.D.
Kenneth Peters, M.D.
Eleanor Anton, R.N.
Loni Lampkins
248-551-0885
NEW YORK, Rochester
University of Rochester
Robert Mayer, M.D.
Edward M. Messing, M.D.
Kay Rust, R.N., M.S.N., F.N.P.
Elizabeth Smith, B.S.
716-275-0133
OKLAHOMA, Oklahoma City
University of Oklahoma
Daniel J. Culkin, M.D.
James F. Donovan Jr., M.D.
Lynda Kelsey, R.N., M.S.
Karen Mataranglo, R.N.
405-271-6900
PENNSYLVANIA, Philadelphia
University of Pennsylvania
George W. Drach, M.D.
Philip Hanno, M.D.
Eric Rovner, M.D.
Alan J. Wein, M.D.
Marilou Foy, R.N.
Gloria McNamara, R.N
215-349-5874
DATA COORDINATING CENTER
University of Pennsylvania, Philadelphia
J. Richard Landis, Ph.D.
Kathleen J. Propert, ScD
Journal
The Journal of Urology