Evaluating Cell Therapy as a Therapeutic Option for Chronic Fecal Incontinence
Key Findings
- A clinical trial across 25 sites worldwide is assessing the effectiveness of cell therapy to reinforce weakened tissue associated with fecal incontinence
- Autologous muscle-derived cell therapy involves harvesting and then transplanting a patient's own muscle cells to repair weakened muscle tissue
- The randomized, double-blind clinical trial is enrolling a large patient cohort to expand on smaller studies reporting the method's safety and efficacy
Physician-scientists at Massachusetts General Hospital are leading a clinical trial evaluating a new therapeutic approach for a stigmatizing and isolating condition. Members of the Center for Pelvic Floor Disorders at Mass General are marshaling their national and international reputation to identify effective treatment options for fecal incontinence (FI), a condition often overlooked in medical research.
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"We established the Center to promote research targeting conditions that are incredibly difficult to treat and leave many patients suffering in silence," says Liliana Bordeianou, MD, MPH, professor of surgery at Mass General and co-director of the Center for Pelvic Floor Disorders. "This trial reinforces our commitment to finding answers for conditions that shouldn't be ignored."
Addressing an Intractable Condition
FI is caused by structural damage to the muscles and nerves involved with bowel movements. Although several risk factors predispose FI, the most common in women is trauma associated with pregnancy, which can also adversely affect the pelvic floor. Most of the approaches to managing FI are not curative, and many available treatments fail to address the condition's underlying causes.
Also frustrating for both clinicians and patients is that each therapeutic approach — surgery, dietary modifications, medication, and physiotherapy — can result in unpredictable patient-specific outcomes.
"Most of our patients end up combining multiple treatments that may or may not additively result in a higher overall reduction of symptoms," says Dr. Bordeianou.
In the case of FI, Dr. Bordeianou explains that the landscape of treatment options is extremely limited for a condition that can result in otherwise healthy individuals experiencing a severely degraded quality of life and rarely leaving their homes.
"Therapeutic success using currently available treatments is defined as a 50% reduction in episode frequency or severity," she says.
That level of efficacy also represents the threshold used by the Food and Drug Administration to approve any treatment targeting FI.
Founded 15 years ago, the Center for Pelvic Floor Disorders seeks to solve these problems via increased awareness of and research into the multifactorial causes and symptoms associated with pelvic floor disorders and associated conditions in both men and women. As a multidisciplinary collaboration between colorectal surgeons, gastroenterologists, gynecologists, urologists, and physical therapists, the Center sees patients with disorders and conditions, including FI, that are among the most difficult to effectively treat.
"Unfortunately, current therapies rarely, if ever, translate to a complete cure, though they do usually offer improvements in a patient's quality of life," explains Dr. Bordeianou. "This underscores the need for innovative approaches that offer more effective and longer lasting options."
Answering the Challenge
The stigma surrounding FI can result in patients feeling isolated and reluctant to seek help. This isolation exacerbates both their challenges and those faced by researchers attempting to recruit statistically significant numbers of study participants. For the DigniFI clinical trial, the Center is addressing this through recruiting that targets a robust local patient contingent and an equally strong network of national and international collaborations.
The study's target population is women suffering from chronic FI as a consequence of obstetric anal sphincter injury (OASI). Eligibility criteria for the study include:
- Adult female (aged 18 years or older) demonstrating FI symptoms for at least 12 months
- Documented history of OASI (e.g., episiotomy or perineal tear)
- Failure of standard treatment regimens for at least six consecutive months
- Compliance with study procedures and willingness to provide written informed consent for study participation
Dr. Bordeianou says that these criteria match those of a previous cohort that showed a positive response to iltamiocel, a type of autologous muscle-derived cell therapy. This therapy requires collecting a small sample of a patient's muscle cells and isolating a particular cell subtype that plays a role in muscle repair.
"We collect muscle from the patient's thigh under local anesthesia," explains Dr. Bordeianou. "The cells are then extracted, processed, and concentrated into a formulation that can be injected back into the patient at the site of the damage."
Among the cells collected, muscle progenitor cells are isolated and expanded. Although normally inactive in healthy tissue, these cells proliferate and differentiate in response to damage, forming new muscle fibers that incorporate with surrounding tissue and vasculature. For DigniFI study participants, the hope is that these injected cells will engraft into damaged or weakened sphincter tissue and subsequently repair structure and function.
The demonstrated efficacy of the approach in a smaller study was sufficient motivation to move toward evaluating it in a much larger, randomized, double-blind clinical trial. Dr. Bordeianou and her collaborators are currently making progress in enrolling over 200 patients across 25 sites worldwide. The rationale for reinforcing elements of the pelvic floor as a treatment modality has previously been established using biological or synthetic materials. However, many of these treatments are no longer available due to safety concerns.
"By using the patient's own cells as the material, we've already addressed issues associated with other techniques attempting to address this condition," she says. "We're committed to revealing whether this method can offer patients an effective and potentially long-term treatment option."
Finding Answers in the Questions
Dr. Bordeianou emphasizes that the Center's track record of success is a direct reflection of the unique ecosystem of Mass General, its focus on collaborative research, and prioritizing patients as the beneficiaries of those efforts. The Center's reputation has resulted in a loyal and ever-growing population of patients grateful to have found a motivated collection of experts. That loyalty has paid dividends for the DigniFI trial.
"We're already approaching the maximum number of patients that we're allowed to recruit at our site," says Dr. Bordeianou.
A big reason for this is that many of the women have been cared for at the Center for over a decade. The clinicians know these patients and their conditions and have shared the ups and downs of different treatment courses.
"Our multidisciplinary meetings often involve discussions of what a given patient is facing and whether any new treatments might make a difference in the status of their condition," Dr. Bordeianou explains.
This process of asking hard questions and challenging each other to think beyond the confines of currently available therapies changes how they approach problems, which serves both their research and patients near and far.
"As colleagues and collaborators, we teach each other from what the patients teach us, which ultimately benefits everyone."