Clinical trial NCT04734847: Motor Cortical Neuromodulation in Women With Interstitial Cystitis/Bladder Pain Syndrome
Official title: Motor Cortical Neuromodulation in Women With Interstitial Cystitis/Bladder Pain Syndrome: Reducing Pain by Improving Brain and Muscle Activity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Interstitial Cystitis
Bladder Pain Syndrome
Keywords: Chronic Pain
Transcranial Magnetic Stimulation
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2021-02-02
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Longer-term Pain
timeFrame: Before first treatment to 3 weeks after last treatment
measure: Shorter-term Pain
timeFrame: Before first treatment to 1 day later just before second treatment
measure: Global Response Assessment
timeFrame: 3 weeks after last treatment
Secondary outcomes:
measure: fALFF in Pelvic-SMA
timeFrame: One hour before and one hour after first treatment
measure: Pelvic floor muscle activity
timeFrame: Just before to between five and ten minutes after start of first treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
Study officials:
affiliation: University of Southern California
name: Jason J Kutch, PhD
role: PRINCIPAL_INVESTIGATOR
References: