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

Interstitial Cystitis Clinical Trial

— IcBrainStim  

Official title:

Motor Cortical Neuromodulation in Women With Interstitial Cystitis/Bladder Pain Syndrome: Reducing Pain by Improving Brain and Muscle Activity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04734847
• Other study ID #: APP-20-05139
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2021
• Est. completion date: August 15, 2025

Study information

• Verified date: May 2024
• Source: University of Southern California
• Contact: Jason J Kutch, PhD
• Phone: 323-442-2932
• Email: kutch[@]pt.usc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 15, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Pain Syndrome
• Cystitis
• Cystitis, Interstitial
• Interstitial Cystitis
• Somatoform Disorders
• Syndrome

Intervention

Device:
• Repetitive Transcranial Magnetic Stimulation (rTMS)
Non-invasive magnetic stimulation of the brain
• 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.

Locations

Country	Name	City	State
United States	University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Longer-term Pain	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.	Before first treatment to 3 weeks after last treatment
Primary	Shorter-term Pain	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.	Before first treatment to 1 day later just before second treatment
Primary	Global Response Assessment	Global Response Assessment (GRA)	3 weeks after last treatment
Secondary	fALFF in Pelvic-SMA	Change in fractional amplitude of low-frequency fluctuations (fALFF) derived from functional magnetic resonance imaging (fMRI) in targeted region of the brain (pelvic-SMA)	One hour before and one hour after first treatment
Secondary	Pelvic floor muscle activity	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.	Just before to between five and ten minutes after start of first treatment