Neuromodulation Therapy for Fecal Incontinence
Condition: Fecal Incontinence
MeSH terms: Fecal Incontinence
Study type: Interventional

Summary: 
      Fecal Incontinence (FI) affects 8-15 % of the US population, predominantly women and elderly,
      and 45% of nursing home residents. It significantly impairs quality of life and poses a major
      health care burden. FI is characterized by significant neuromuscular dysfunction of the
      pelvic floor that includes bilateral lumbo-anorectal and sacro-anorectal neuropathy and
      sensori-motor dysfunction. This multifactorial etiology suggests that maladaptive
      neuroplastic changes in the neural innervation of lower gastrointestinal tract could play a
      significant role in the pathogenesis of FI. A critical barrier to progress in the treatment
      of FI is the lack of understanding of how treatments affect the core pathophysiological
      mechanisms of FI, and the absence of mechanistically based non-invasive therapies. Our goal
      is to address the problem of FI by developing therapies that modulate peripheral and central
      neuronal perturbations and thereby improve visceromotor control and sensori-motor
      dysfunctions, and to understand the neurobiologic basis of these treatments. Our central
      hypothesis is that a novel non-invasive treatment consisting of repetitive translumbar
      magnetic stimulation (rTLMS) and repetitive transsacral magnetic stimulation (rTSMS) will
      significantly improve FI by enhancing peripheral and central neural excitability and will
      provide a multidimensional therapeutic benefit- enhance anal muscle strength, improve stool
      perception and improve rectal capacity. Our approach is based on our preliminary studies
      which suggest that repetitive translumbar magnetic stimulation (rTLMS) and transsacral
      magnetic stimulation (rTSMS) improve anorectal pain and neuropathy and induce central
      neuroplastic changes.

      Our objectives are to:

        1. address the significant gap in our knowledge regarding the peripheral and central
           neuroenteric axis and how perturbations in the afferent and efferent neural signaling
           can affect FI;

        2. develop a new treatment for FI with repetitive magnetic stimulation and determine the
           feasibility, safety and optimal frequency setting of rTLMS and rTSMS;

        3. determine the mechanistic basis for this neuromodulation therapy;

        4. identify if the locus for improvement lies in the afferent or efferent signaling or
           both.
    

Detailed description: 
      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).
    

Intervention name(s): Repetitive lumbosacral magnetic stimulation (rTLSMS)
Intervention type(s): Procedure
Intervention description(s): Patients randomized to Six sessions of weekly therapy with either 1 HZ or 5 Hz or 15 Hz magnetic stimulations of the lumbar and sacral regions.
Other intervention name(s): rTLSMS
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment