Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Translumbosacral Neuromodulation for FI (TNT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03899181
Recruitment Status : Not yet recruiting
First Posted : April 2, 2019
Last Update Posted : April 2, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Massachusetts General Hospital
Information provided by (Responsible Party):
Satish Rao, Augusta University

Tracking Information
First Submitted Date  ICMJE February 20, 2019
First Posted Date  ICMJE April 2, 2019
Last Update Posted Date April 2, 2019
Estimated Study Start Date  ICMJE April 2019
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
  • AIM 1:Change in weekly Fecal Incontinence (FI) episodes [ Time Frame: 6 weeks (short term) ]
    A responder will be defined as a patient who shows at least 50% reduction in FI episodes/week when compared to baseline.
  • AIM 2: Latencies for lumbo-anal Magnetic Evoked Potentials (MEP) responses [ Time Frame: 6 weeks ]
    The bilateral latencies, amplitudes and area under the curve (AUC) for the lumbo-anal MEP responses will be measured.
  • AIM 2: Latencies for sacro-anal MEP responses [ Time Frame: 6 weeks ]
    The bilateral latencies, amplitudes and area under the curve (AUC) for the sacro-anal MEP responses will be measured.
  • AIM 2: Latencies for the ano-cortical Cortical Evoked Potentials (CEP) response. [ Time Frame: 6 weeks ]
    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.
  • AIM 3:Change in weekly FI episodes [ Time Frame: 48 weeks (long term) ]
    A responder will be defined as a patient who shows at least 50% reduction in FI episodes/week when compared to baseline.
  • AIM 3: Latencies for lumbo-anal MEP responses [ Time Frame: 48 weeks ]
    The bilateral latencies, amplitudes and area under the curve (AUC) for the lumbo-anal MEP responses will be measured.
  • AIM 3: Latencies for sacro-anal MEP responses [ Time Frame: 48 weeks ]
    The bilateral latencies, amplitudes and area under the curve (AUC) for the sacro-anal MEP responses will be measured.
  • AIM 3: Latencies for the ano-cortical CEP response. [ Time Frame: 48 weeks ]
    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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
  • Stool Frequency [ Time Frame: 6 weeks, 48 weeks ]
    Stool frequency-how often subjects have a bowel movement.
  • Stool consistency [ Time Frame: 6 weeks, 48 weeks ]
    Stool consistency (Bristol Stool scale, 1-7). 1-very hard stool, 4-normal, smooth stool, and 7-watery stool
  • Bowel Urgency [ Time Frame: 6 weeks, 48 weeks ]
    Severity of Bowel urgency-Unable to postpone BM for more than 15 Minutes? YES/NO
  • Reduction of Fecal Incontinence (FI) episodes [ Time Frame: 6 weeks, 48 weeks ]
    Percentage of subjects with 100% and 75% reduction in FI episodes
  • Stool Leakage Characteristics [ Time Frame: 6 weeks, 48 weeks ]
    Leakage characteristics-amount 0. None
    1. Mild
    2. Moderate
    3. Excessive
  • Global Assessment of bowel satisfaction [ Time Frame: 6 weeks,, 48 weeks ]
    using 7 point Likert scale (1. Considerably relieved; 7-considerably worse)
  • Global Assessment of bowel satisfaction-Visual Analog Scale [ Time Frame: 6 weeks, 48 weeks ]
    0 (absent)-10 (very severe) point visual analog scale (VAS)
  • FI severity-Fecal Incontinence Severity Index (FISI) [ Time Frame: 6 weeks,4 8 weeks ]
    Fecal Incontinence Severity Index (FISI)-assessed on characteristics of accidental bowel leakage: 1: 2 or More times a day and 6: Never any symptom
  • FI severity-Fecal Incontinence Severity Score (FISS): [ Time Frame: 6 weeks, 48 weeks ]
    Fecal Incontinence Severity Score (FISS): 5 questions asking about severity of their fecal incontinence. Not a scale.
  • FI severity-International Consultation on Incontinence Questionnaire (IC-IQB): [ Time Frame: 6 weeks, 48 weeks ]
    International Consultation on Incontinence Questionnaire (IC-IQB): Questionnaire asking several questions about bowel symptoms. There are scales within each question: 0: never-4:always. How much does this (symptom) bother you? 0 (not at all) and 10 (a great deal).
  • Change in FI Quality of Life (FI-QOL) [ Time Frame: 6 weeks, 48 weeks ]
    A 4 question questionnaire that assesses the quality of life with FI symptoms. 2 questions have scaled questions: 1 (most of the time) 4 (none of the time) and 1(strongly agree) 4 (Strongly disagree)
  • Psychological Function PROMIS anxiety Questionnaire [ Time Frame: 6 weeks, 48 weeks ]
    Questionnaire that assesses anxiety symptoms. Asks questions on a scale of 1 (never) and 5 (always).
  • Psychological Function PROMIS Depression Questionnaire [ Time Frame: 6 weeks, 48 weeks ]
    Questionnaire that assesses Depression symptoms. Asks questions on a scale of 1 (never) and 5 (always).
  • Psychological Function PROMIS Efficacy Questionnaire [ Time Frame: 6 weeks, 48 weeks ]
    Questionnaire that assesses self-efficacy for managing symptoms. Asks questions on a scale of 1 (I am not at all confident) and 5 (I am very confident).
  • Amplitudes (Milivolts of the nerve) for lumbo-rectal MEP [ Time Frame: 6 weeks, 48 weeks ]
    of the lumbo-rectal MEP responses.
  • Amplitudes (Milivolts of the nerve) for sacro-rectal MEP [ Time Frame: 6 weeks, 48 weeks ]
    Milivolts of the nerve for the sacral-rectal MEP.
  • Amplitudes (Milivolts of the nerve) for recto-cortical CEP responses [ Time Frame: 6 weeks, 48 weeks ]
    Milivolts of the nerve for the recto-cortical CEP responses.
  • MEP Index The area under the curve of the MEP response [ Time Frame: 6 weeks, 48 weeks ]
    The area under the curve of the MEP response
  • Anal Sphincter Function-Sustained Squeeze Pressure [ Time Frame: 6 weeks, 48 weeks ]
    Anal sustained squeeze pressure (mm Hg) measure from Anal rectal manometry study.
  • Anal Sphincter Function-Anal Resting Pressure [ Time Frame: 6 weeks, 48 weeks ]
    Anal resting pressure (mm Hg) measure from Anal rectal manometry study.
  • Anal Sphincter Function-Squeeze Pressure [ Time Frame: 6 weeks, 48 weeks ]
    Anal squeeze pressure (mm Hg) measure from Anal rectal manometry study.
  • Rectal Sensation-First Sensation (volume of air) [ Time Frame: 6 weeks, 48 weeks ]
    During anal manometry test, subject tells investigator when they feel a first sensation of the balloon inside their rectum. (measure in mL of air).
  • Rectal Sensation- Desire to defecate [ Time Frame: 6 weeks, 48 weeks ]
    During anal manometry test, subject tells investigator when they feel a desire to defecate from the balloon that is blown up inside their rectum. (measure in mL of air).
  • Rectal Sensation-Urgency to Defecate [ Time Frame: 6 weeks, 48 weeks ]
    During anal manometry test, subject tells investigator when they feel an urgency to defecate from the balloon that is blown up inside their rectum. (measure in mL of air).
  • Rectal Sensation-Maximum tolerable volume [ Time Frame: 6 weeks, 48 weeks ]
    During anal manometry test, subject tells investigator when they feel have a maximum tolerable volume (as much as they can handle) from the balloon that is blown up inside their rectum. (measure in mL of air).
  • Rectal Compliance [ Time Frame: 6 weeks, 48 weeks ]
    Assessed by dv/dp
  • Symptoms correlation [ Time Frame: 6 weeks, 48 weeks ]
    Correlate bowel symptoms (FI episodes), severity and physiological changes with MEP and CEP latency.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Translumbosacral Neuromodulation for FI
Official Title  ICMJE Translumbosacral Neuromodulation Therapy For Fecal Incontinence: Randomized Trial
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 that includes lumbosacral neuropathy, anorectal sensori-motor dysfunction, and maladaptive pelvic floor-brain innervation. A critical barrier to progress in the treatment of FI is the lack of randomized controlled trials, absence of mechanistically based non-invasive therapies that modify disease, and a lack of understanding on how treatments affect pathophysiology of FI, as highlighted by experts at a recent NIDDK workshop. 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 peripheral and central neuronal perturbations and thereby improve sensory and visceromotor 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, and thereby provide a multidimensional therapeutic benefit. Our approach is based on compelling preliminary study which showed that TNT at 1 Hz frequency, significantly improved FI, by enhancing bidirectional gut and 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 spino-anorectal and afferent pelvic floor-brain signaling, and anorectal sensori-motor function; 3) identify the durability of treatment response and neuromodulatory effects of TNT, and whether reinforcement TNT provides augmented improvement through enhanced adaptive neuroplasticity, 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 for FI, a scientific basis for the development of this treatment, and improved understanding of the pathophysiology of FI and the neurobiologic mechanism(s) of 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.
Detailed Description

Fecal incontinence (FI), defined as the involuntary passage of either formed or liquid stool, affects 8-15% of ambulatory Americans, mostly women and elderly and 45% of nursing home residents. It occurs at least weekly in 3% of adults, and in 37% of patients attending primary care clinics. FI has a major impact on quality of life, causes significant distress including anxiety and depression, and carries a considerable health care burden. FI is characterized by multifactorial dysfunctions that include lumbosacral neuropathy, anorectal sensori-motor dysfunction, and decreased rectosigmoid reservoir capacity and maladaptive pelvic floor-brain innervation. Consequently, treatments that help a single dysfunction, for example, anal dextranomer injection or anal sphincteroplasty could improve FI by reinforcing the anal barrier, but unlikely to improve the multidimensional problem of FI. Also, anal sphincteroplasty felt to be effective initially, was disappointing long-term with only 30% remaining continent at 10 years. An-other surgical procedure, sacral nerve stimulation (SNS) has been shown to be useful in 54% of FI patients, but has significant complications (33%) and a failure rate of 15%, its mechanism of action is unknown, and lacks rigorous sham-controlled trial. Furthermore, a comparative assessment of the effectiveness of current treatments has not been performed, and none of the current therapies have been shown to improve the multifactorial pathophysiological dysfunction(s) in FI.

A critical barrier to progress in the treatment of FI is the lack of RCTs, and absence of mechanistically based non-invasive therapies that modify the pathophysiology of FI. Consequently, most current remedies have remained ineffective. These findings were highlighted by experts at a recent NIDDK workshop focused on research in FI. Our long-term goal is to address the problem of lack of effective treatments for FI by investigating therapies that modulate peripheral and central neuronal perturbations, and to understand the neurobiologic basis of these treatments. Translumbosacral Neuromodulation Therapy (TNT) is a novel, non-invasive technique that involves the focal delivery of magnetic energy through an insulated coil to the lumbo-sacral nerves that regulate anorectal function. The pulses generated are of the same strength as clin-ical MRI machines. It builds on the concept of neuromodulation therapies such as repetitive transcranial magnetic stimulation (rTMS) that uses a computerized electromechanical medical device to deliver brief pulses of magnetic energy and has been shown to be effective in major depression , refractory auditory hallucinations (AH), and visceral pain, and our studies in post-stroke dysphagia. Our central hypothesis is that TNT will significantly improve FI, both in the short-term and long-term, by enhancing neural excitability and inducing neuroplasticity, and thereby will provide a multidimensional thera-peutic benefit- improve neuropathy, enhance anal strength, improve rectal perception and capacity.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Fecal Incontinence
Intervention  ICMJE
  • Device: Translumbosacral Neuromodulation Therapy (TNT)
    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.
  • Other: Sham TNT Therapy
    This is the sham TNT treatment as mentioned in the different ARMs using the fake coil with no magnetic stimulations.
Study Arms  ICMJE
  • Active Comparator: 1 Hz 2400 TNT Treatment
    Intervention: TNT treatment intervention with 2400 total stimulations with the magnetic coil..
    Intervention: Device: Translumbosacral Neuromodulation Therapy (TNT)
  • Active Comparator: 1 Hz 3600 TNT Treatment
    Intervention: TNT treatment intervention with 3600 total stimulations with the magnetic coil.
    Intervention: Device: Translumbosacral Neuromodulation Therapy (TNT)
  • Sham Comparator: Sham TNT Treatment
    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.
    Intervention: Other: Sham TNT Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 29, 2019)
132
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2024
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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;
  • impaired cognizance as assessed by the Six-Item Screener.
  • metal implants, pacemakers;
  • previous pelvic surgery/radiation, bladder repair, radical hysterectomy;
  • Ulcerative and Crohn's colitis;
  • rectal prolapse;
  • anal fissure, anal surgery (abscess), congenital anorectal malformation, fistulae or inflamed hemorrhoids;
  • pregnant women
  • nursing mothers.
  • Previous anorectal surgery (STARR, FENIX) except sphincteroplasty.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Satish Rao, MD, PhD 7067212238 srao@augusta.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03899181
Other Study ID Numbers  ICMJE 1303352
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Satish Rao, Augusta University
Study Sponsor  ICMJE Augusta University
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • Massachusetts General Hospital
Investigators  ICMJE Not Provided
PRS Account Augusta University
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP