Translumbosacral Neuromodulation for FI

NCT03899181 | Unknown DMC FDA Device

• 2 other identifiers: 1303352R01DK121003
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 2

Brief Summary

Fecal Incontinence (FI) affects 40 million Americans, predominantly women and elderly. It is a major health care burden, significantly impairs quality of life and psychosocial function. FI is characterized by multifactorial dysfunction including lumbosacral neuropathy, anorectal sensori-motor dysfunction, and abnormal pelvic floor-brain innervation. A critical barrier to progress in the treatment of FI is the lack of RCTs, absence of mechanistically based non-invasive therapies that modify disease, and a lack of understanding on how treatments affect pathophysiology of FI. Consequently, most current remedies remain ineffective. Our long-term goal is to address the problem of lack of effective treatments for FI by investigating treatments that modulate neuronal perturbations and thereby improve sensory and motor control, and to understand the neurobiologic basis of these treatments. Our central hypothesis is that a novel, non-invasive treatment consisting of Translumbosacral Neuromodulation Therapy (TNT), using repetitive magnetic stimulation, will significantly improve FI in the short-term and long-term, by enhancing neural excitability and inducing neuroplasticity. Our approach is based on compelling pilot study which showed that TNT at 1 Hz frequency, significantly improved FI, by enhancing bidirectional gut- brain signaling, anal sphincter strength and rectal sensation compared to 5 or 15 Hz. Our objectives are to 1) investigate the efficacy, safety and optimal dose of a new treatment, TNT, in a sham controlled, randomized dose-dependent study in 132 FI patients; 2) determine the mechanistic basis for TNT by assessing the efferent and afferent pelvic floor-brain signaling, and sensori-motor function; 3) identify the durability of treatment response and effects of TNT, and whether reinforcement TNT provides augmented improvement, by performing a long-term, sham controlled randomized trial. Our expected outcomes include the demonstration of TNT as a durable, efficacious, safe, mechanistically based, non-invasive, and low risk treatment for FI. The impact of our project includes a novel, disease modifying, non-invasive treatment, a scientific basis for this treatment, and improved understanding of the pathophysiology of FI and how TNT modifies bidirectional gut and brain axes and anorectal function. Ultimately, the knowledge generated by this project will provide new avenues for the development of innovative, evidence-based therapies for FI.

Conditions

Fecal Incontinence

Outcome Measures

Primary Outcomes (8)

• AIM 1 Primary Outcome measure is the proportion of patients achieving >50% of reduction in fecal incontinence episodes/weeks at the end of 6 weeks compared to baseline.

  A responder will be defined as a patient who shows at least 50% reduction in FI episodes/week when compared to baseline.

  6 weeks (short term)

• AIM 2: Latencies for lumbo-anal Magnetic Evoked Potentials (MEP) responses compared to baseline

  The bilateral latencies, amplitudes and area under the curve (AUC) for the lumbo-anal MEP responses will be measured.

  6 weeks

• AIM 2: Latencies for sacro-anal MEP responses compared to baseline

  The bilateral latencies, amplitudes and area under the curve (AUC) for the sacro-anal MEP responses will be measured.

  6 weeks

• AIM 2: Latencies for the ano-cortical Cortical Evoked Potentials (CEP) responsecompared to baseline.

  The bilateral latencies, amplitudes and area under the curve (AUC) for the anal CEPs will be averaged to measure the latency of each component, P1, N2, etc, and mean group data.

  6 weeks

• AIM 3:Primary Outcome measure is the proportion of patients achieving >50% of reduction in fecal incontinence episodes/weeks at the end of 48 weeks compared to baseline.

  A responder will be defined as a patient who shows \> 50% reduction in FI episodes/week at the end of 48 weeks compared to baseline

  48 weeks (long term)

• AIM 3: Latencies for lumbo-anal MEP responses

  The bilateral latencies, amplitudes and area under the curve (AUC) for the lumbo-anal MEP responses will be measured.

  48 weeks

• AIM 3: Latencies for sacro-anal MEP responses

  The bilateral latencies, amplitudes and area under the curve (AUC) for the sacro-anal MEP responses will be measured.

  48 weeks

• AIM 3: Latencies for the ano-cortical CEP response .

  The bilateral latencies, amplitudes and area under the curve (AUC) for the anal CEPs will be averaged to measure the latency of each component, P1, N2, etc, and mean group data

  48 weeks

Secondary Outcomes (27)

• Stool Frequency

  6 weeks, 48 weeks

• Stool consistency

  6 weeks, 48 weeks

• Bowel Urgency

  6 weeks, 48 weeks

• Reduction of Fecal Incontinence (FI) episodes

  6 weeks, 48 weeks

• Stool Leakage Characteristics

  6 weeks, 48 weeks

Study Arms (3)

1 Hz 2400 TNT Treatment

ACTIVE COMPARATOR

Intervention: TNT treatment intervention with 2400 total stimulations with the magnetic coil..

Device: Translumbosacral Neuromodulation Therapy (TNT)

1 Hz 3600 TNT Treatment

ACTIVE COMPARATOR

Intervention: TNT treatment intervention with 3600 total stimulations with the magnetic coil.

Device: Translumbosacral Neuromodulation Therapy (TNT)

Sham TNT Treatment

SHAM COMPARATOR

This arm will have the sham treatment session. First we will assess the motor threshold intensity described above. Next, a sham coil is placed on each of 4 regions (2 lumbar \& 2 sacral), and 600 stimulations will be given at each site in 2 trains, with a 5 minutes rest period between each site and 3 minutes between trains.

Other: Sham TNT Therapy

Interventions

Translumbosacral Neuromodulation Therapy (TNT) DEVICE

A probe with 2 pairs of bipolar steel ring electrodes, will be placed in the rectum. At each site a mapping procedure is performed with single stimulus coil to assess the motor threshold intensity, defined as the minimum level of magnetic stimulation intensity required to achieve an anal and rectal MEP response of 10 microvolts and an anterior tibialis MEP of 20 microvolts with 50% of trials.The intensity for TNT at each site is capped at a maximum of 150% above this threshold to comply with safety guidelines. Thus, intensity of magnetic stimulations will be individualized. Bilateral lumbar stimulations (rTLMS) are administered at L2/L3 disc space, and sacral stimulations (rTSMS) at S2/S3 level. Next a 70 mm double air film self-cooling coil is positioned randomly over one of the 4 sites, held in place by a coil fixator and 300 or 450 stimulations are delivered. After a 5 min rest the cycle is repeated (Total =600-900/site).The coil is moved to the opposite side and it is repeated.

1 Hz 2400 TNT Treatment; 1 Hz 3600 TNT Treatment

Sham TNT Therapy OTHER

This is the sham TNT treatment as mentioned in the different ARMs using the fake coil with no magnetic stimulations.

Sham TNT Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent episodes of FI for 6 months;
• No mucosal disease (colonoscopy + biopsy); and
• On a 2-week stool diary patients reported at least one episode of solid or liquid FI/week.

You may not qualify if:

• severe diarrhea (\>6 liquid stools/day, Bristol scale \>6);
• on opioids,);
• active depression;
• severe cardiac disease, chronic renal failure or previous GI surgery except cholecystectomy and appendectomy;
• neurologic diseases (e.g. head injury, epilepsy, multiple sclerosis, strokes, spinal cord injury) and increased intracranial pressure;
• metal implants (within 30 cm of magnetic coil placement), pacemakers;
• previous pelvic surgery/radiation, radical hysterectomy;
• Ulcerative and Crohn's colitis;
• rectal prolapse;
• active anal fissure, anal abscess, congenital anorectal malformation, fistulae or inflamed hemorrhoids;
• pregnant women

Sponsors & Collaborators

• Augusta University: lead
• National Institutes of Health (NIH): collaborator
• Massachusetts General Hospital: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Augusta University

Augusta, Georgia, 30912-4810, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114-2621, United States

RECRUITING

MeSH Terms

Conditions

Fecal Incontinence

Condition Hierarchy (Ancestors)

Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Satish Rao, MD,PhD

  Augusta University

  STUDY DIRECTOR

Central Study Contacts

Satish Rao, MD, PhD

CONTACT

7067212238; srao@augusta.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Director of Neurogastroenterology/Motility

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: April 2, 2019
• Study Start: June 5, 2019
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2025
• Last Updated: July 21, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)