Investigation of Potential Therapeutic Effects of Pulsed Electromagnetic Field for the Treatment of Symptoms Associated With Interstitial Cystitis/Bladder Pain Syndrome
Phase: NA
Conditions: Interstitial Cystitis, Chronic Interstitial Cystitis, Bladder Pain Syndrome
Sponsor: Wake Forest University Health Sciences

 
 
Revised 08-13-2020 
 
 
 
Study Title: Investigation of Potential Therapeutic Effects of Pulsed 
Electromagnetic Field for the Treatment of Symptoms Associated with Interstitial 
Cystitis/Bladder Pain Syndrome 
 
 
IRB00068066 
 
 
 
NCT04540887 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Revised 08-13-2020 
 
Study Title: Investigation of Potential Therapeutic Effects of Pulsed Electromagnetic Field 
for the Treatment of Symptoms Associated with Interstitial Cystitis/Bladder Pain 
Syndrome 
 
Background, Rationale and Context 
 
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a clinical diagnosis based primarily on 
chronic symptoms of pain perceived by the patient to emanate from the bladder and/or pelvis 
associated with urinary urgency or frequency in the absence of another identified cause for the 
symptoms1. Although it is not a life-threatening disease, the chronicity and severity of pain, 
along with urinary symptoms, causes great impairment in a patient’s quality of life2. IC/BPS 
poses as a significant clinical challenge for many reasons. For one, the pathophysiology 
described in the literature is incompletely determined and likely multi-factorial, including factors 
such as inflammation, neurovascular dysfunction, ion imbalance, and impaired urothelial cell 
integrity3,4,5. Consequently, there are many options for IC/BPS therapy, many of which are 
driven primarily by patient-reported symptoms. In this regard, IC/BPS patients with moderate to 
severe pain typically require multi-modal therapy, often resulting in incomplete or no resolution 
of symptoms. Another clinical challenge is the heterogeneity of the symptoms. While pelvic pain 
is the distinguishing characteristic, patients with IC/BPS also routinely present with additional 
urological and non-urological medical symptoms and syndromes6,7. This has led to the 
description of two specific sub-phenotypes in IC/BPS based on anesthetized bladder capacity 
(BC), in which patients with BC < 400 cc are more likely to experience severe pain, urgency and 
frequency (bladder centric sub-phenotype), and patients with BC > 400 cc (non-bladder centric 
sub-phenotype) have a higher prevalence of non-urological associated syndromes (NUAS) such 
as fibromyalgia, chronic fatigue symptoms, irritable bowel syndrome, endometriosis and sicca 
syndrome8,9. 
 
The current landscape of IC/BPS therapies is vast and imperfect, with the level of invasiveness 
ranging broadly from lifestyle and behavioral changes to total cystectomy (for refractory end-
stage disease). Current non-invasive treatments, including behavioral changes, dietary 
restrictions, and pelvic floor physical therapy have shown benefits in pain mitigation, but may 
not demonstrate consistent efficacy in more severe cases10. Pharmacologic strategies, such as 
NSAIDs and opiates, have also shown little evidence demonstrating consistent efficacy for 
treating the chronic pain state, and certainly are not without adverse effect profiles11. More 
invasive modalities such as cystoscopy with hydrodistention, botulinum toxin injections, or total 
cystectomies carry morbidity and procedural risk. Furthermore, there is a clear need for a new 
therapeutic strategy for IC/BPS management, as there is currently no standardized approach that 
provides relief for all, or even most, patients.  
 
Pulsed Electromagnetic Field (PEMF) therapy may present a promising alternative therapy for 
IC/BPS. PEMF is a safe, non-invasive, and effective therapy currently used for wound healing, 

 
 
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bone-related diseases (osteoarthritis, RA), and chronic pain states (chronic lower back pain, 
fibromyalgia), the latter of which is frequently associated with IC/BPS as NUAS. Based on 
Faraday’s law, electromagnetic interactions (e.g. PEMF) with biological processes and 
conditions (e.g. IC/BPS) will theoretically address many of the proposed pathophysiological 
causes of the condition. While the mechanism(s) of action are not fully understood, PEMF 
therapy has been shown in several studies (randomized, double-blinded, placebo-controlled 
trials) to decrease the output of pro-inflammatory proteins, improve oxygenation of blood and 
tissue, stabilize transmembrane action potential and ion channels, and stimulate tissue 
regeneration12-15. Thus, PEMF may provide a safe, non-invasive therapeutic option that would be 
complementary to, or serve as an alternative for, the treatments that are currently being 
administered in IC/BPS for pain reduction. Of note, PEMF has demonstrated an excellent safety 
profile with no associated systemic risks reported to date16.  Additionally, the application of 
exogenous PEMF to stimulate the pelvic floor muscle has recently been introduced for treating 
urge and/or stress urinary incontinence and overactive bladder17.  Furthermore, if patient safety 
and efficacy for pain reduction are demonstrated, these feasibility studies will provide the 
foundation for larger multi-site trials to determine additional parameters regarding the 
appropriate number of treatments as well as the duration of benefit (pain relief) following 
treatments. 
 
Objectives 
 
The objective of this pilot study is to test the idea that PEMF therapy will serve as a safe, non-
invasive therapeutic modality that can effectively improve the chronic pain and/or associated 
symptoms of IC/BPS patients. We hypothesize that PEMF therapy will result in significant pain 
reduction in IC/BPS patients, specifically those with a non-bladder centric phenotype. 
 
Published results from randomized, double-blinded, placebo-controlled clinical trials that have 
evaluated the efficacy of PEMF for pain management in conditions such as lower back pain, 
osteoarthritis, rheumatoid arthritis, and fibromyalgia have all reported significant pain reduction 
following PEMF therapy. Chronic pelvic pain and widespread, non-localized pain (beyond the 
bladder) are common findings in many IC/BPS patients. The proposed mechanism of action of 
PEMF therapy (increased microcirculation and tissue regenerative capacity through modulation 
of inflammatory processes) provides a compelling rationale for evaluating the efficacy of PEMF 
in IC/BPS patient pain relief. 
 
Methods and Measures 
 
Design 
This is a single center clinical series evaluating symptom relief following a 4-week trial of 
PEMF therapy. From our registry of IC/BPS patients we will recruit women, ages 18-80, who 

 
 
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have met all inclusion and exclusion criteria, which includes demonstration of an anesthetic BC 
> 400 cc (non-bladder-centric phenotype) and a current numeric rating scale (NRS) pain score 
for pelvic pain ≥ 6. Upon enrollment, each patient will be taught how to administer home 
treatment with the BEMER (Bio Electro Magnetic Energy Regulation) PEMF devices which 
consist of a total body mat (B.Body) plus a targeted pelvic mat (B.Pad). Following the brief in-
clinic training, participants will be sent home with the PEMF devices (pre-set to deliver the same 
level of energy each time) and will self-administer 8 minute PEMF therapy sessions, twice daily 
(once in the morning, once in the evening). 
 
Patient assessments will occur at three time points: (1) enrollment, (2) after four weeks of 
treatment, and (3) at twelve weeks post-enrollment. The primary outcome measure will be the 
change in NRS pain score for pelvic pain. A decrease of at least 2 points on the NRS pain scale 
will be considered as representative of a significant decrease in pelvic (and/or widespread) pain. 
Secondary outcomes will be assessed by validated IC/BPS questionnaires (O’Leary-Sant 
indices), voiding characteristics (patient recorded voiding diary), change in perceived pain as 
determined by pain body maps, and the patient’s overall impression of change (Global Response 
Assessment). Follow-up assessments will be completed remotely through phone or email 
surveys. During the twelve-week study, patients will not undergo any of the following IC/BPS 
therapies: cystoscopy with hydrodistention, bladder instillations, or trigger point injections. 
Patients that were prescribed a stable dose of pro re nata (PRN) narcotic medication at least three 
months prior to enrollment will be included in the study. Patients will be expected to report 
which, if any, pain medications they have been taking prior to enrollment and what additional 
medications they plan to use throughout the duration of the study. The following IC/BPS oral 
medications will be allowed during this time: amitriptyline, cimetidine, hydroxyzine, and 
pentosan polysulfate. 
 
The demographic data will be extracted from patient’s electronic medical record. The basic 
office evaluation will be composed of detailed medical history, physical exam, urinalysis, urine 
culture, 7-daysvoiding diary, O’Leary-Sant symptom and problem index (ICPI/ICSI), Pelvic 
Pain and Urgency/Frequency Patient Symptom (PUF) scale, Genitourinary Pain Index (GUPI), 
SF-36 quality of life questionnaires, and numeric rating scale for pain in the last 24 hours.  
 
In this proof of concept study, all participants will receive the full therapy (i.e. there will not be a 
control group). In the double-blind placebo-controlled crossover trial that will follow this proof-
of-concept study, we will have access to placebo (sham) mats for use as a control.  
 
Subject Selection Criteria 
 
Participants will be recruited from the Urology Clinic at Wake Forest Baptist Hospital and all 
study participants will provide written informed consent. 

 
 
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• Inclusion Criteria 
Female patients between 18 to 80 years with a previously established clinical diagnosis of 
IC/BPS. Participants must have an anesthetic BC > 400 cc, a current NRS score ≥ 6, and 
have no cognitive deficits.  Patients will be required to attest that they will not receive a 
new prescription and/or an increased dose of narcotic medication while participating in 
the study.  
 
• Exclusion Criteria 
Any history of bladder, uterine, ovarian, or vaginal cancer, urethral diverticulum, spinal 
cord injury, stroke, Parkinson’s disease, multiple sclerosis, spina bifida, radiation cystitis, 
cyclophosphamide treatment, immunosuppressive therapy in consequence of 
transplantation, allogeneic cellular transplantation, or bone marrow or stem cell 
transplantations, deep vein thrombosis, or genital herpes. Patients will be excluded from 
this study if they have an implanted pace-maker, metal prosthesis, urinary tract infection, 
BMI > 40, or are currently pregnant. 
 
• Sample Size 
For this small pilot study, we will enroll up to 10 study patients with the goal of 
achieving a full dataset from at least 6 patients.  
 
 
Human Subjects Protection 
 
Informed Consent:  An IRB-approved written informed consent will be obtained from each 
subject. Patients will initially be contacted and introduced to the study via phone call from a 
study team member to discuss study details and answer questions. If they agree, an electronic 
copy of the IRB-approved consent form will be e-mailed to the patient. Informed consent and 
signature will be acquired in the Wake Forest University Urology Outpatient Clinic prior to 
training on the PEMF device. 
 
Confidentiality and Privacy:  Confidentiality will be protected by collecting only information 
needed to accomplish future demographic matching (i.e. patient’s age, ethnicity, BMI, etc.), 
minimizing to the fullest extent possible the collection of any information that could directly 
identify subjects, and maintaining all study information in a secure manner.  To help ensure 
subject privacy and confidentiality, a unique study identifier will appear on the data collection 
form.  Any collected patient identifying information corresponding to the unique study identifier 
will be maintained on a separate master log.  The master log will be kept secure, with access 
limited to designated study personnel.  Following data collection, subject identifying information 
will be destroyed at the earliest opportunity consistent with data validation and study design, 

 
 
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producing an anonymous analytical data set.  Data and records will be kept locked and secured, 
with access limited to study staff and password protection on all data stored electronically.  No 
reference to any individual participant will appear in reports, presentations, or publications that 
may arise from this study. 
 
Every effort will be made to maintain participant privacy. Data will only be released to scientists 
who are qualified and prepared to conduct a research study. If publications or presentations result 
from this research, participants will not be identified by name or any other personal identifier. 
Data and Safety Monitoring 
 
The principal investigator and study coordinator will be responsible for the overall monitoring of 
the data and safety of study participants and will ensure that the subjects’ information is not 
revealed.  The principal investigator will be assisted by other members of the study staff. 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
 
Any unanticipated problems, serious and unexpected adverse events, deviations, or protocol 
changes will be promptly reported by the principal investigator or designated member of the 
research team to the IRB and sponsor or appropriate government agency if appropriate. 
 
 
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