It’s embarrassing. It’s frustrating. And it significantly impacts the quality of life for more than 15 million women in the United States. “It” is stress urinary incontinence (SUI).
SUI most commonly occurs from the loss of pelvic floor anatomic support of the bladder combined with dysfunction of the urinary sphincter. Those suffering from the condition know all too well that something as simple as a light sneeze can cause urine leakage. The contributing causes to SUI are multifactorial and include muscle weakening from childbirth, some medications, hormonal deficiencies, urethral injury, smoking, obesity, excess consumption of caffeine or alcohol over time, and years of high impact activities.
Current therapies range from Kegel exercises and bladder training to inserted devices, bulking agents, and surgical options. Vanderbilt University Medical Center hopes to add to that armamentarium by serving as the principal investigation site for a clinical trial evaluating a new biologic approach to SUI.
The Autologous Muscle-Derived Cells (AMDC) for Female Urinary Incontinence Sphincter Repair trial utilizes cells derived from a woman’s own muscle tissue to strengthen the sphincter muscle. The sixth study in the therapy’s development protocol, this Phase III clinical trial is available at 20 sites in the United States. The randomized, double-blind, placebo-controlled trial has begun enrolling qualified patients to assist investigators in efforts to obtain Food & Drug Administration approval to bring the promising cellular technology by Cook MyoSite to market.
Roger Dmochowski, MD, professor of Urologic Surgery at VUMC, serves as principal investigator for the Nashville site. Melissa Kaufman, MD, PhD, assistant professor of Urologic Surgery, serves as study co-investigator at Vanderbilt and as the national principal investigator for the entire trial.
“Stress incontinence really is an astonishingly common condition,” Kaufman said. She added the projected prevalence between 26-44 percent of adult females is probably substantially underestimated because of a hesitation by women to discuss the condition … even with their healthcare providers.
Previous trials were primarily focused on the safety of this new biologic therapy, which requires a biopsy of a participant’s leg to harvest starter cells that are then sent to a lab for expansion before being implanted in the woman’s urethral sphincter. From those earlier trials, Kaufman noted, “We haven’t seen any long term complications of concern – no tumorigenicity and complications from the injections and biopsy have all been transient.”
The results, though, have been very encouraging. “In these early trials, a high percentage of patients demonstrated a 50 percent reduction in stress leaks, and it has been maintained at 12 months,” she said. Kaufman added several Vanderbilt patients who participated in the Phase II trial still have complete continence four-five years out from the procedure.
To participate in this final phase of investigation, potential candidates must have had some stress incontinence symptoms for at least six months and have tried a more conservative therapy without resolution of the issue. All participants will undergo the leg biopsy to secure starter cells. Then, the women will either receive a reinjection of their own cells or the placebo control dose.
Kaufman noted, “We are looking to enroll 267 women in the United States with a 2:1 ratio of cells to placebo.” However, she continued, “Even women who are in the placebo arm can cross over and receive active agent at the 12-month time period.”
Using an electronic diary, study participants will record data on voids, leakage, fluid intake, and pad tests for a three-day period around follow-up appointments at one, three, six, 12 and 24 months. Researchers also hope to pinpoint optimal dosing. Compared to lower dose groups in previous studies, those in the 100 and 200x106 groups had the best results in stress leak reduction and pad weight at 12 months. However, all dose groups in the previous studies had statistically significant improvement in quality of life questionnaire scores at the one-year mark.
As for the science behind the results, Kaufman said there are several potential mechanisms that explain the improvement. “One can be actual regrowth and regeneration in the sphincter muscle,” she explained. Another might be a paracrine role where the deposited cells augment the muscle that is already in place, allowing for new growth.
Because both mechanisms rely on regenerative properties, Kaufman said patients typically begin to see improvement three to six months after the intrasphincteric injection. “It is reconstituting the sphincter so it’s an actual biologic effect rather than bulking,” she explained. “I truly believe this is a new paradigm in treatment for women with stress urinary incontinence.”
Kaufman pointed out, “Women need options and alternatives to surgical treatments. This entire therapy is office-based, which makes it very attractive.” In fact, she said, the FDA has given Cook MyoSite a special protocol leading to expedited approval pending outcomes meeting expectations in this Phase III trial. Assuming earlier findings are borne out in this final phase, she said the therapy could be widely available to women within the next few years.
Kaufman added there are numerous other potential applications for AMDC that Vanderbilt researchers hope to explore in the future as part of the quest to bring novel, minimally invasive treatments to patients that are truly disease modifying.
How to Enroll
If you have a female patient age 18 or older who might be a candidate for participation, please have them call 866-309-6066 or direct them to researchsui.com for eligibility criteria, more information on the study, and a national pre-screening survey.
