The University of Pittsburgh and Magee-Womens Research Institute were one of nine participating sites of an National Institutes of Health (NIH)-sponsored Pelvic Floor Disorders Network study that compared an implantation of a neuromodulation unit to bladder injections of Botox to help women suffering from bladder incontinence.
Dr. Halina Zyczynski, medical director of Magee-Womens Hospital of UPMC’s Center for Continence and Pelvic Floor Disorders, answers questions about the study and its important findings.
What is bladder incontinence and what are some traditional therapies women opt for?
A: Urinary incontinence is the involuntary leakage of urine. There are different reasons for loss of bladder control. One of the most bothersome reasons is unexpected bladder muscle spasms, which usually cause a sense of bladder pressure and urgency to urinate. We refer to this as urgency urinary incontinence. First- and second- line therapies offered to improve the symptoms of urgency urinary incontinence include reducing the amount of liquid drunk each day to reducing dietary bladder irritants such as caffeine and artificial sweeteners. People can also benefit from pelvic floor muscle training (a very specific form of physical therapy) and medication.
You were recently the principal investigator for Magee-Womens Hospital of UPMC for a multi-site trial that compared third-line therapies of Botox and sacral neuromodulation. How do these treatments help with bladder incontinence?
A: One of the major causes for urgency urinary incontinence is a malfunctioning of the nerve signals between the central nervous system, the brain and the bladder muscle. The brain through the spinal cord is constantly delivering a message for the bladder muscles to relax, stretch and accommodate or hold the urine made by the kidneys. When there is a “hiccup” or “static” in the message to keep the bladder muscle relaxed, it can contract or cramp. Unfortunately, the commonly prescribed oral medications for urgency incontinence are insufficient or poorly tolerated by some patients. It’s they who are offered “third” line therapies of Botox injection or implantation of a neuromodulation unit. An injection of Botox into the bladder muscle works by relaxing the twitchy or overactive bladder muscles. A sacral neuromodulation works like a pacemaker for the bladder muscle. The electrical stimulator suppresses the spasms by sending electrical pulses to nerves in the spine that control the bladder muscle. Up to this point, doctors and patients did not know if one of the third-line treatments was better than the other, and for whom.
How was the research conducted?
A: The ROSETTA study involved 381 women from nine U.S. medical centers, including Magee. These women reported having at least six urgency incontinence episodes per day, and also reported that they had not improved with other treatments, such as oral medication. The participants were randomly assigned to either receive sacral neuromodulation or a Botox injection. After a trial period to test their responsiveness to the therapies, 364 women were enrolled and followed for six months after treatment. The study team analyzed the number of urgency incontinent episodes in monthly “bladder diaries” along with other measures of symptom bother and satisfaction with the treatment.
What were the results from the study?
A: Participants who received botulinum toxin saw their number of daily urgency incontinent episodes decrease by 3.9 leaking episodes on average versus 3.3 in the sacral neuromodulation group. The difference was statistically significant. Botox participants also reported a greater reduction in bothersome symptoms, higher satisfaction with treatment, and a greater likelihood of endorsing the treatment. Additionally, among participants who completed at least four monthly diaries, a higher percentage of Botox participants saw at least a 75-percent reduction in or complete resolution of urgency incontinent symptoms. However, we also found that when compared to the neuromodulation group, participants in the Botox group reported a higher number of urinary tract infections. Botox also caused temporary inability to empty the bladder completely, which required the use of a catheter.
What is the significance of these findings?
A: This was a valuable study to participate in because it’s the first randomized trial comparing the efficacy of two U.S. Food and Drug Administration-approved, third-line therapies in a severely affected population. This information should help guide care for women suffering from bladder incontinence, helping patients and providers choose between the two treatments.