A noninvasive translumbosacral neuromodulation therapy (TNT) significantly improved fecal incontinence (FI) symptoms compared with sham treatment in a multicenter randomized sham-controlled trial of patients with recurrent episodes of FI that was unresponsive to conservative therapy. Patients receiving active magnetic stimulation achieved responder rates ranging from 66% to 81% versus 32% with sham treatment after six weeks of therapy, according to a study published in Gastroenterology.
“Fecal incontinence is a very common problem affecting 9% of the U.S. population. There are limited treatment options with very few randomized controlled trials (RCTs), and there are no long-term RCTs,” said Satish SC Rao, MD, PhD, FRCP, J. Harold Harrison, MD, Distinguished University Chair in Gastroenterology, Professor of Medicine, Director, Neurogastroenterology and Motility, Director, Digestive Health Clinical Research Center, Wellstar MCG Health, Augusta University.
In the Phase 3 double-blind trial, the researchers enrolled 109 ambulatory adult patients at two U.S. academic centers between 2019 and 2024 to assess the efficacy and safety of TNT in patients with FI.
Eligible participants had at least one episode of solid or liquid FI weekly despite diet modification, fiber supplementation, antidiarrheals and Kegel exercises. Patients were randomly assigned to receive TNT with either 2,400 or 3,600 repetitive magnetic stimulations, or sham stimulation, delivered weekly for six weeks at four sites bilaterally — two lumbar and two sacral sites.
Active therapy improved responder rates
The primary endpoint was a 50% or greater reduction in weekly FI episodes recorded in prospective electronic stool diaries. Researchers reported responder rates of 66% in the 2,400-pulse group and 81% in the 3,600-pulse group compared with 32% in the sham group. Patients receiving 2,400 pulses had nearly four times the odds of response versus sham treatment, while patients receiving 3,600 pulses had more than eight times the odds of response. The difference between the two active-treatment groups was not statistically significant.
Secondary outcomes favored TNT
Secondary endpoints also favored active treatment. A 75% or greater reduction in FI episodes occurred more frequently in both translumbosacral neuromodulation groups than in the sham group.
Weekly FI episodes declined from 8.3 to 3.5 in the 2,400-pulse group and from 7.5 to 2.8 in the 3,600-pulse group, compared with a reduction from 6.6 to 4.6 in the sham group. Improvements emerged as early as week one.
Patients receiving active therapy also experienced reductions in stool frequency and urgency-related episodes. Weekly stool frequency decreased by about five bowel movements in the 3,600-pulse group and by about three in the 2,400-pulse group, compared with about two in the sham group. The proportion of FI episodes associated with strong urgency decreased by 15 percentage points in the 2,400-pulse group and 20 percentage points in the 3,600-pulse group, whereas urgency increased slightly in the sham group.
Fecal Incontinence Severity Index scores improved significantly with active therapy. Scores decreased by 8.6 points in the 2,400-pulse group and 5.6 points in the 3,600-pulse group compared with a 1.4-point reduction in the sham group. Quality-of-life measures improved from baseline across all four FI quality-of-life domains in the active-treatment groups, although between-group differences were not significant.
Neurophysiologic measures improved
The study also evaluated objective physiologic outcomes. Nearly 90% of patients had evidence of neuropathy at one or more lumbosacral sites with no differences between groups.
Baseline motor evoked potential latencies were prolonged across all groups compared with healthy controls, indicating lumbosacral neuropathy. Following TNT, patients in both active-treatment groups showed significant improvements in lumboanal, sacroanal and lumborectal nerve conduction measures compared with sham treatment and baseline values, except for the right lumboanal motor evoked potential. Anal maximal and sustained squeeze pressures also increased significantly in the 2,400- and 3,600-pulse groups but not in the sham group.
“This sham-controlled study met the primary outcome by demonstrating significant improvements in FI episodes in both the TNT groups when compared to sham group,” said Dr. Rao. “TNT, a novel, non-invasive, outpatient-based treatment, was safe, well tolerated and efficacious in improving FI symptoms, its severity and lumbosacral neuropathy in patients with moderately severe FI.”
Safety profile and limitations
The researchers reported no treatment-related serious adverse events. Serious adverse events requiring hospitalization included a fall, urosepsis and viral hepatitis, all of which were adjudicated as unrelated to study treatment. Back pain occurred in two patients in each study group. One patient each in the active-treatment groups reported tingling or numbness and urinary urgency. Two patients in the 3,600-pulse group had deep vein thrombosis, though both had preexisting risk factors.
The researchers noted several limitations, including underrepresentation of male patients, potential performance bias because the treatment administrators were not blinded and the possibility that the sham coil delivered low-level magnetic stimulation. They also stated that longer-term durability remains under investigation in an ongoing sham-controlled study. They also noted that the lower baseline FI frequency in the sham group may have contributed to lesser improvement, although they considered this unlikely.
After six weeks of short-term therapy
According to Dr. Rao, after the initial six weeks of short-term therapy there were 32% responders in the sham arm and 68% responders in the 2,400 magnetic stimulations arm and 84% responders in the 3,600 stimulations arm. Patients who received 2,400 or 3,600 stimulations were invited to participate in the long term (one-year) study and were re-randomized to either active treatment or sham treatment.
“The active treatment group showed a 91% responder rate at one-year, whereas those who received active treatment initially and sham treatment for long term showed a responder rate of 74% — i.e., there was some loss of efficacy but still a durable response,” Dr. Rao explained.
“TNT is safe and efficacious and shows a durable response after initial therapy and for those receiving monthly treatments there was a higher responder rate at one year,” Dr. Rao noted.
Potential clinical implications
Dr. Rao said that TNT is a novel, outpatient, one-hour treatment session that confers significant and superior clinical benefit in patients with FI when compared to sham treatment after one year, and reverses the underlying neuropathy.
“This is a significant advance over our current treatment modalities and targets a novel new pathway,” said Dr. Rao. “If adopted widely this could be a game changer in the management of FI patients and provide long-lasting relief, safely and inexpensively.”
Next steps
The equipment for magnetic stimulation and neurophysiology are not routinely available in GI labs but mostly available with neurologists and psychiatrists, noted Dr. Rao. “So, gastroenterologists will have to adopt this new technology and there is a short learning curve. Future research should test better methods of delivering this therapy [such as] more sessions per week or shorter duration, and further clinical trials in the community may provide additional support.”
Dr. Rao reported holding a patent for translumbosacral neuromodulation therapy.