Sacral Nerve Stimulation Can Relieve Interstitial Cystitis, Studies Suggest

ANAHEIM, Calif. - June 4, 2001 - Results from three new studies being presented here this week at the annual meeting of the American Urological Association (AUA) may provide new hope for patients suffering from a painful bladder condition called interstitial cystitis (IC). The findings of two separate pre-clinical trials both suggest that a therapy involving mild electrical stimulation of the sacral nerves may prove to be an effective new treatment for patients with severe IC. In addition, the results of new laboratory research may help to explain the method by which sacral nerve stimulation works in the body. The independent studies each investigated the treatment, also known as sacral neuromodulation. The sacral nerves, which are located near the base of the spinal cord in the lower back, control the bladder, bowel and pelvic organs. By stimulating the nerves, physicians can often control bladder function. Interstitial cystitis is a chronic, inflammatory condition of the bladder wall that affects an estimated one million Americans. It primary strikes women around the age of 40, although 25 percent of women with IC are under the age of 30 and the condition can affect children and men as well. Its cause is unknown, and at present there is no cure nor is there a universally effective treatment. Symptoms of IC include bladder pain, urinary urgency, day and night urinary frequency (up to 60 times per 24-hour period), suprapubic (lower abdominal) or perineal (the area between scrotum and anus in men; vagina and anus in women) pain and pressure. IC can also lead to pain during sexual intercourse.

The first study, titled “Sacral Neuromodulation in Patients with Interstitial Cystitis: A Multi-Center Clinical Trial,” was conducted at three sites within the United States and involved a total of 22 women with IC. All of the patients experienced urinary frequency, urgency and pelvic pain and each had previously been treated unsuccessfully with standard therapies such as oral medications and medications placed directly into the bladder. The clinical trial sites included Stanford University Medical Center, Stanford, Calif.; William Beaumont Hospital, Royal Oak, Mich.; and Graduate Hospital, Philadelphia, Pa.

Patients underwent a three- to seven-day test of sacral nerve stimulation on an outpatient basis. Among the patients in the study, sacral nerve stimulation was shown to significantly reduce urinary urgency and frequency, and in some patients, pain as well.Sacral neuromodulation also led to a significant increase in the force of the urinary stream. Although the improvement in the average degree of urinary urgency was not statistically significant, indirect measures of urgency (such as average volume and maximum volume voided, and feeling of bladder emptiness) did show a statistically significant improvement.

“Our results suggest that sacral neuromodulation may represent a new therapeutic option for IC patients with severe IC who are refractory to other standard forms of therapy,” said Christopher K. Payne, M.D., assistant professor of urology at the Stanford University School of Medicine and co-chair of the study. "Acute testing clearly demonstrated an overall improvement in essentially all symptoms associated with this common and debilitating condition. Naturally, these short-term results will require confirmation with long-term follow-up after implantation of a permanent device.”

The findings of the second study, titled “Neuromodulation Treatment for Refractory Severe Interstitial Cystitis,” was conducted at the University of Oklahoma Health Science Center in Oklahoma City, and involved 17 patients - 15 women; two men - with documented severe refractory IC.

Of the nine patients who experienced successful test stimulation (±75 percent improvement in symptoms), eight underwent surgery to receive the neuromodulation device. Due to surgical complications, two patients later opted to have the devices removed; but among the remaining six, all continued to receive relief for an average of 18 months. Five of the patients experienced such good responses that they were able to stop taking their medications altogether.

“Interstitial cystitis that is refractory and severe appears to have an effective treatment with sacral neuromodulation,” said Daniel J. Culkin, M.D., professor and chair of urology at Oklahoma University Health Science Center and principal investigator in the study. “We observed a positive response to the therapy. Of the patients who successfully used the devices for at least 18 months, all showed results that continued to last throughout the full three years of the study. Although additional large clinical trials will need to be conducted in the future, neuromodulation may offer a chance for a more normal life for patients who fail to respond to other forms of treatment.”

Results from a laboratory research project titled “Neuromodulation Reduces Spinal Cord Expression of Nitric Oxide Synthase in Rats with Interstitial Cystitis,” conducted by investigators from Toronto Hospital in Ontario, Canada, help shed light on the method of action of sacral neuromodulation in IC. Previous studies have shown that chronic noxious stimulation of the bladder lining - essentially what occurs in patients with IC - can cause cells in the spinal cord to overproduce an enzyme called nitric oxide synthase (NOS).

The investigators studied laboratory rats with a condition that mimicked IC to determine whether the over expression of NOS was affected by neuromodulation. The animals were divided into three groups: the first had the condition and were treated with neuromodulation; the second had the condition but received no treatment; and the rats in the last group, which were healthy and untreated, served as the control. Among the group with the IC-like condition that received neuromodulation, the researchers noted a significant reduction in NOS when compared to the group with the untreated condition.

“According to our findings, sacral neuromodulation in an animal model reduces spinal cord expression of NOS in interstitial cystitis,” said Magdy Hassouna, M.D., Ph.D., senior scientist, Division of Applied and Interventional Research, Toronto Western Research Institute, and the study’s principal investigator. “This is important because for the first time, it provides an understanding of how neuromodulation may work.” With this knowledge, researchers may someday be able to refine current neuromodulation techniques so that more patients with IC can receive effective treatment.

The ICA is committed to promoting and providing research funding to find effective treatments - and, eventually, a cure - for IC,” said Vicki Ratner, M.D., founder, president and chief medical officer of ICA. “And at the core of our mission is a commitment to provide patients with the most comprehensive and up-to-date information available about interstitial cystitis. To this end, we are encouraged by ongoing research such as these studies presented at the AUA Annual Meeting. Sacral neuromodulation may be a valuable therapeutic option for patients suffering from severe IC who have not found relief using standard IC therapies. Our hope is that these findings will provide encouragement for people suffering with IC, and motivate scientists around the globe to continue the quest for safe and effective therapies.”

Sacral nerve stimulation (SNS) is delivered via an implantable system that includes a thin insulated wire called a lead, a neurostimulator similar to a cardiac pacemaker, and an extension. It is known that sacral neuromodulation is effective for the treatment of several bladder control problems. This knowledge led researchers to investigate whether SNS could also provide relief for the symptoms of IC. Sacral nerve stimulation is currently approved by the U.S. Food and Drug Administration (FDA) to treat three bladder control problems: urinary urge incontinence; nonobstructive urinary retention; and urgency-frequency. Sacral neuromodulation is investigational for the treatment of IC.

First-line treatments that can provide relief for some patients include behavioral techniques (healthy lifestyle habits, diet modification, biofeedback, bladder retraining, pelvic muscle exercises), oral medications (Elmiron, anticholinergics, antispasmodics, or tricyclic antidepressants), and intravesical medications. There are also several FDA-approved surgical procedures to treat IC; but unlike sacral neuromodulation, they are irreversible. These procedures, which are seldom effective and are usually considered a last resort, include bladder augmentation, bladder denervation, and bladder removal.

The Interstitial Cystitis Association (ICA), based in Rockville, Maryland, is a not-for-profit voluntary health agency, dedicated to providing support and information to patients, education of the lay and medical communities, and promotion and funding for IC research. In existence since 1984, the ICA has funded more than $1,000,000 in research. The ICA’s leadership includes founder, president and chief medical officer Vicki Ratner, M.D., and a medical advisory board of distinguished physicians and researchers. The ICA provides quarterly publications for researchers and clinicians, as well as patients and their families. These publications, as well as the ICA’s comprehensive Web site (www.ichelp.org), feature the most current information on IC, including the most effective treatments available, as well as those currently undergoing clinical trials. The ICA works closely with the National Institutes of Health (NIH) and Congress to ensure funding for interstitial cystitis research.