Motor Cortical Neuromodulation in Women With Interstitial Cystitis/Bladder Pain Syndrome (IcBrainStim)

• ClinicalTrials.gov Identifier: NCT04734847
• Recruitment Status: Recruiting
• First Posted: February 2, 2021
• Last Update Posted: June 8, 2021
• Sponsor: University of Southern California
• Information provided by (Responsible Party): Jason Kutch, University of Southern California

Study Description

Brief Summary:

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a common, chronic, and debilitating condition in women. Preliminary evidence suggests that IC/BPS pain can be reduced applying non-invasive repetitive transcranial magnetic stimulation (rTMS) to areas of the brain that regulate pelvic floor muscle activity. However, prior studies have examined rTMS in a very limited sample and have not examined changes in brain or pelvic floor muscle activity to determine the mechanism of rTMS for IC/BPS. This study is designed to directly address these limitations.

Condition or disease	Intervention/treatment	Phase
Interstitial Cystitis; Bladder Pain Syndrome	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); Device: Sham Repetitive Transcranial Magnetic Stimulation (Sham-rTMS)	Not Applicable

Detailed Description:

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a common, chronic, and debilitating condition in women. The underlying cause of IC/BPS remains unknown. We recently published the first functional magnetic resonance imaging (fMRI) study comparing brain function in women with IC/BPS to healthy women. We found that women with IC/BPS have altered resting activity in supplementary motor area (SMA). Specifically, these changes appear in a part of SMA that we have shown to control pelvic floor muscle activity. We call this part of SMA "pelvic-SMA". Our results provide the first potential explanation for extensive published reports of increased pelvic floor muscle activity in women with IC/BPS. We hypothesize that we are observing evidence of an important theory of chronic pain: motor cortical changes occur that are initially beneficial to increase protective muscle activity but are ultimately maladaptive and perpetuate pain. If this theory is true, it should be possible to reduce pain and muscle activity by improving brain activity. The proposed work is to do exactly that. Using non-invasive repetitive transcranial magnetic stimulation (rTMS) directed at pelvic-SMA, we aim to determine if we can reduce pain (Aim 1), improve resting brain activity (fMRI) and resting pelvic floor muscle electromyographic (EMG) activity in IC/BPS (Aim 2), and to link the pain reductions to fMRI/EMG improvements to develop a causal mediation model of IC/BPS symptoms (Aim 3). We will recruit 50 women with IC/BPS to participate in the study, and participants will be randomized to 2 groups of 25: high-frequency (active) or sham (inert). Our preliminary data suggest that high-frequency stimulation is the best stimulation protocol for reducing pain and improving pelvic-SMA activity and resting pelvic floor muscle activity. Our preliminary results agree with a large body of literature suggesting that high-frequency rTMS applied to motor cortex is the best stimulus paradigm to reduce pain, but our proposed work has the potential to greatly innovate the field of non-invasive brain stimulation for pain by providing a mechanism by which the stimulation can improve deficiencies in motor function in chronic pain patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Motor Cortical Neuromodulation in Women With Interstitial Cystitis/Bladder Pain Syndrome: Reducing Pain by Improving Brain and Muscle Activity
• Actual Study Start Date: June 1, 2021
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: April 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: High-frequency rTMS; Intensity: rTMS treatment intensity determined using resting motor threshold (RMT). Treatment will be delivered at 80% of the RMT. Site of Stimulation: Region of supplementary motor area (SMA) that regulates pelvic floor muscle activity. This target is defined in Montreal Neurological Institute (MNI) Coordinates of X=-2, Y=-16, and Z=68 mm. Frequency: 10 Hz. Duration: 20 Trains, 10 second duration, 50 second inter-train interval. Total number of pulses per session: 2000. Total number of session: 5 (one session per day for 5 consecutive days).	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); Non-invasive magnetic stimulation of the brain
Sham Comparator: Sham rTMS; Identical to the High-frequency rTMS arm except delivered with an inert "sham" stimulation coil.	Device: Sham Repetitive Transcranial Magnetic Stimulation (Sham-rTMS); Device that appears identical to the active rTMS device, but does not produce any magnetic field and does not stimulate the brain.

Outcome Measures

Primary Outcome Measures :

1. Longer-term Pain [ Time Frame: Before first treatment to 3 weeks after last treatment ]
   Change in Visual Analog Scale of Pain. This scale ranges from 0 (no pain) to 10 (worst pain imaginable), so higher scores indicate more pain.
2. Shorter-term Pain [ Time Frame: Before first treatment to 1 day later just before second treatment ]
   Change in Visual Analog Scale of Pain. This scale ranges from 0 (no pain) to 10 (worst pain imaginable), so higher scores indicate more pain.
3. Global Response Assessment [ Time Frame: 3 weeks after last treatment ]
   Global Response Assessment (GRA)

Secondary Outcome Measures :

1. fALFF in Pelvic-SMA [ Time Frame: One hour before and one hour after first treatment ]
   Change in fractional amplitude of low-frequency fluctuations (fALFF) derived from functional magnetic resonance imaging (fMRI) in targeted region of the brain (pelvic-SMA)
2. Pelvic floor muscle activity [ Time Frame: Just before to between five and ten minutes after start of first treatment ]
   Change in activity of pelvic floor muscles as measured by electromyography (EMG). EMG is a physiological parameter measuring the electrical potential generated by a muscle, indicative of its activity. EMG is measured in micro-volts and then converted to percent change.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Be at least 18 years old.
2. Be female.
3. Have a diagnosis of IC/BPS by the referring physician, with urologic symptoms present a majority of the time during the most recent 3 months
4. Screen within standard limits for pelvic pain

Exclusion Criteria:

1. Symptomatic urethral stricture
2. On-going neurological conditions affecting the bladder or bowel
3. Active auto-immune or infectious disorders
4. History of cystitis caused by tuberculosis or radiation or chemotherapies
5. History of non-dermatologic cancer
6. Current major psychiatric disorders
7. Severe cardiac, pulmonary, renal, or hepatic disease
8. Conditions or the use of medical devices that are contraindications for either fMRI or rTMS procedures, including pregnancy, seizure disorders, or chronic headaches

Contacts and Locations

Contacts

Contact: Jason J Kutch, PhD; 323-442-2932; kutch@pt.usc.edu

Contact: Larissa V Rodriguez, MD; 310-601-3366; lrodriguez@med.usc.edu

Locations

United States, California

University of Southern California; Recruiting

Los Angeles, California, United States, 90049

Contact: Jason J Kutch, PhD 323-442-2932 kutch@usc.edu

Sponsors and Collaborators

University of Southern California

Investigators

• Principal Investigator: Jason J Kutch, PhD; University of Southern California

More Information

• Responsible Party: Jason Kutch, Associate Professor, University of Southern California
• ClinicalTrials.gov Identifier: NCT04734847
• Other Study ID Numbers: APP-20-05139
• First Posted: February 2, 2021
• Last Update Posted: June 8, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Jason Kutch, University of Southern California:

Chronic Pain; Transcranial Magnetic Stimulation

Additional relevant MeSH terms:

Cystitis; Cystitis, Interstitial; Syndrome; Somatoform Disorders; Disease; Pathologic Processes; Mental Disorders; Urinary Bladder Diseases; Urologic Diseases