The National Institute of Diabetes & Digestive & Kidney Diseases

The Interstitial Cystitis Clinical Trials Group, Randomized Clinical Trial of Elmiron® and Atarax®

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 Interstitial Cystitis (IC) Clinical Trials Group studied IC patients who had unremitting urinary frequency and pain or discomfort that lasted at least 24 weeks. The interventional trial tested oral drugs pentosan polysulfate sodium (Elmiron®) and hydroxyzine hydrochloride (Atarax®).

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.

"IC leaves many people unable to cope with basic daily functions," says Leroy M. Nyberg Jr., M.D., Ph.D., director of urology research at the National Institute of Diabetes and Digestive and Kidney Diseases, which is funding the clinical trial. "This is the first of a series of rigorous treatment trials. Our ultimate goal is to be able to recommend to physicians those therapies most likely to relieve symptoms in subgroups of patients."

Participants were divided into four groups to receive either (1) a placebo, (2) Elmiron®, (3) Atarax®, or (4) both active drugs for 6 to 16 months, depending on when they joined. The study required clinic visits, symptom questionnaires, medical history and physical exams, voiding diaries, and urine and blood samples. At the end of the study, doctors compared self-reported symptom improvement between the placebo and drug groups.

Results

The 18-month pilot study of the two commonly available treatments showed no significant benefit in patients with interstitial cystitis (IC). 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. The results are reported in the September 2003 issue of the Journal of Urology .

"We believe that IC may be caused by many different factors," said 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 ).

Interstitial Cystitis Clinical Trials Centers and Investigators