Neuromodulation Therapy for Fecal Incontinence

Our expected outcome include development of new treatment approaches for FI which are
mechanistically based, effective, safe, low cost, less invasive, low risk and less dependent
on patient compliance.

The impact of our project include a new non-invasive treatment modality for FI, a scientific
basis for the development of this treatment and improved understanding of the peripheral and
central neuroenteric axis in FI.

Aim 1: Test the hypothesis that neuromodulation therapy with combined repetitive translumbar
magnetic stimulation (rTLMS) and transsacral magnetic stimulation (rTSMS) improves symptoms
in FI patients. Investigators will evaluate the efficacy, safety and optimal frequency
setting of rTLMS and rTSMS for FI by investigating whether 6 sessions of weekly therapy with
1 Hz or 5Hz or 15 Hz magnetic stimulations of the lumbar and sacral regions provides
therapeutic response in FI patients. Investigators will randomize 48 patients with FI and
assess symptoms and anorectal function. The primary outcome measure will be the reduction in
number of episodes of FI. The secondary outcome measures will be i) bowel symptoms/severity
(FISI, FICA), ii) quality-of-life (FI-QOL), iii) psychosocial function, iv) anal sphincter
pressures, v) rectal sensation, vi) rectal compliance. A safety assessment will monitor
adverse effects.

Aim 2: Test the hypothesis that repetitive translumbar magnetic stimulation (rTLMS) and
transsacral magnetic stimulation (rTSMS) will improve FI symptoms and anorectal function
through modulation of ascending and descending signaling pathways in the neuroenteric axis.
Investigators will investigate the mechanistic basis for rTLMS/rTSMS therapy by examining the
neuroenteric axis. Investigators will examine rectal and anal motor evoked potentials (MEPs)
in 48 FI patients with transcranial, translumbar and transsacral magnetic stimulations
(descending signaling), before and after 6 sessions of therapy with 1 Hz or 5 Hz or 15 Hz
magnetic stimulations. Also, investigators will examine the cortical evoked potentials (CEP)
after anal and rectal stimulation (ascending signaling). investigators will determine whether
rTLMS and rTSMS therapy shortens latency and increases amplitude and area under curve (AUC)
of anal and rectal MEPs and ano-cortical and recto-cortical CEPs when compared to baseline.
Investigators will identify if the locus for improvement lies in the afferent signaling,
efferent signaling or both and whether the neuroplastic changes are central or peripheral.
The primary outcome measure for efferent signaling will be the latency of lumbo-anal and
sacro-anal MEP responses and for afferent signaling will be the latency of ano-cortical CEP.
Secondary outcome measures include anal and rectal electrical sensory thresholds,
lumbo-rectal and sacro-rectal MEPs and recto-cortical CEPs and correlations of FI episodes
and bowel symptoms with changes in latency and MEP measurements.

Participants will maintain a two week prospective fecal incontinence symptom diary. Baseline
questionnaires will be administered. Patients demonstrating at least one episode of fecal
incontinence per week, on average, will be eligible, pending all other eligibility criteria
is met. Patients will come for brain-gut assessment (as above) as well as baseline anorectal
manometry (if needed per protocol specifications). Patients will be randomized to one of the
three hertz groups and have treatment one within one week of baseline assessments. A total of
six weekly treatments (with a +7 day window allowed), will occur. After the six treatments,
patients will have all baseline assessments repeated (brain-gut assessments, anorectal
manometry and questionnaires).

Inclusion Criteria:

1. Recurrent episodes of FI for 6 months;

2. No mucosal disease (colonoscopy + biopsy); and

3. On a 2-week stool diary patients reported at least one episode of solid or liquid
FI/week.

Exclusion Criteria: Patients with

1. severe diarrhea (>6 liquid stools/day, Bristol scale >6);

2. on opioids, tricyclics (except on stable doses > 3months);

3. active depression;

4. comorbid illnesses, severe cardiac disease, chronic renal failure or previous
gastrointestinal surgery except cholecystectomy and appendectomy;

5. neurologic diseases (e.g. head injury, epilepsy, multiple sclerosis, strokes, spinal
cord injury);

6. impaired cognizance (mini mental score of < 15/25) and/or legally blind;

7. metal implants, pacemakers;

8. previous pelvic surgery, bladder repair, radical hysterectomy;

9. ulcerative and Crohn's colitis;

10. rectal prolapse, anal fissure, anal surgery or inflamed hemorrhoids;

11. pregnant women

12. nursing mothers.