Clinical trial NCT06013449: Efficacy of Pulsed Electromagnetic Field and Heparin/Bupivacaine Instillations
Official title: Investigation of the Effect of Simultaneous Pulsed Electromagnetic Field (PEMF) and Intravesical Heparin - Bupivacaine Cocktail Instillation for the Symptomatic Treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Interstitial Cystitis
Chronic Interstitial Cystitis
Bladder Pain Syndrome
Keywords: interstitial cystitis
bladder pain syndrome
painful bladder
chronic pelvic pain
urinary urgency
urinary frequency
pulsed electromagnetic field
PEMF
bladder instillation
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2023-08-28
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a sham-control, single-blind clinical series. Following in-clinic training, half of the participants will be sent home with Pulsed Electromagnetic Field (PEMF) devices (pre-set to deliver the same level of energy each time) and the other half will be sent home with sham mats. The sham device is identical in every way to the treatment device except the sham console does not deliver a pulsed electromagnetic field. Patients will be randomly assigned (1:1) to either the PEMF treatment or the sham device. Both groups will be instructed on how to self-administer PEMF therapy for 8 minutes. All participants will be instructed to only use the PEMF devices immediately following each instillation, while they are holding the instillation solution in their bladder.
Primary purpose: TREATMENT

Brief summary: The objective of this study is to test the idea that Pulsed Electromagnetic Field (PEMF) therapy will serve as a safe therapeutic modality that can effectively be administered simultaneously with bladder instillations of a bupivacaine-heparin cocktail to improve the chronic pain and/or associated symptoms of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) patients. The study team will distribute the PEMF device to female adults with IC/BPS who have been prescribed bladder instillations of bupivacaine-heparin to see if PEMF therapy in conjunction with bladder instillations of heparin and bupivacaine may be more effective in reducing pain levels and symptomatology of IC/BPS than instillations alone.

Detailed description: IC/BPS is a chronic condition affecting the urinary bladder, causing generalized pelvic pain and urinary symptoms such as urgency, frequency, and nocturia. Although it is not a life-threatening condition, the chronicity and severity of pain, along with urinary symptoms, can negatively impact a patient's quality of life. IC/BPS poses as a significant clinical challenge for many reasons. Importantly, the pathophysiology is incompletely understood and likely multi-factorial, including factors such as inflammation, neurovascular dysfunction, ion imbalance, and impaired urothelial cell integrity. Consequently, there are many therapeutic options for IC/BPS, 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 routinely present with additional urological and non-urological medical symptoms and syndromes. This has led to the description of two specific sub-phenotypes in IC/BPS based on anesthetic bladder capacity (BC), in which patients with BC ≤ 500 cc are more likely to experience severe pain, urgency and frequency (bladder centric sub-phenotype), and patients with BC \> 500 cc (non-bladder centric sub-phenotype) have a higher prevalence of non-urological associated syndromes (NUAS) such as fibromyalgia, migraines, chronic fatigue symptoms, irritable bowel syndrome, endometriosis and sicca syndrome.

Intravesical bladder instillations have been listed as a treatment option for IC/BPS by the American Urologic Association (AUA). Current evidence supports the use of single or multi-dose regimens of Dimethyl sulfoxide (DMSO), heparin and/or lidocaine. Heparin is a sulfated polysaccharide that is theorized to help restore the bladder's glycosaminoglycan (GAG) layer upon instillation, and multiple studies have demonstrated its effectiveness as an intravesical agent for symptom control. The combination of heparin with local anesthetics such as lidocaine/bupivacaine has been shown to provide even greater symptom relief than heparin alone.

Pulsed Electromagnetic Field (PEMF) therapy is a safe, non-invasive, and effective treatment option currently used for enhanced wound healing, bone-related diseases (osteoarthritis, Rheumatoid arthritis (RA)), and chronic pain states (chronic lower back pain, fibromyalgia), the latter of which is frequently associated with IC/BPS. The proposed mechanism(s) of action of PEMF therapy have 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 regeneration

PEMF therapy in conjunction with intravesical instillations of heparin and lidocaine/bupivacaine may be more effective in reducing pain levels and symptomatology of IC/BPS than instillations alone. Due to PEMF's proposed mechanism of action of improving microcirculation and tissue regenerative capacity, it may be able to augment pain reduction by improving both the protective effect of heparin on the GAG layer and bupivacaine's anesthetic efficacy. Using a randomized, sham-controlled trial design, this study will investigate the potential added therapeutic benefit of simultaneous PEMF therapy in patients who self-administer bladder instillations of heparin-bupivacaine multiple times per week, compared to instillations administered without PEMF.

Eligibility criteria: Inclusion Criteria:

* Previously established clinical diagnosis of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)
* Current Numeric Rating Scale (NRS) greater than or equal to 5
* History of cystoscopy with hydrodistension with bladder capacity determination under anesthesia
* No contraindications to the instillation solution
* No cognitive deficits

Exclusion Criteria:

* History of bladder, ovarian or vaginal cancer
* History of urethral diverticulum
* History of radiation cystitis
* History of spinal cord injury or spina bifida
* History of Parkinson's Disease
* History of Multiple Sclerosis (MS)
* History of Stroke
* History of genital herpes
* History of or current cyclophosphamide treatment
* Current placement of a pacemaker or metal prothesis
* Active urinary tract infection
* BMI \>40
* Residual urine of \>100 cc
* Currently pregnant

Primary outcomes:
measure: Pelvic pain scores as measured by the Brief Pain Inventory (BPI) Short Form - Baseline
timeFrame: Baseline
measure: Pelvic pain scores as measured by the Brief Pain Inventory (BPI) Short Form - Week 3
timeFrame: Week 3
measure: Pelvic pain scores as measured by the Brief Pain Inventory (BPI) Short Form - Week 6
timeFrame: Week 6
Secondary outcomes:
measure: Change in Interstitial Cystitis/ Bladder Pain Syndrome (IC/BPS) scores, as measured by the O'Leary Sant Interstitial Cystitis Symptom Index and Problem Index (ICSI/ICPI)
timeFrame: Baseline, Week 3, and Week 6
measure: Change in Interstitial Cystitis/ Bladder Pain Syndrome (IC/BPS) scores, as measured by the Pelvic Pain and Urgency Frequency (PUF) Patient Symptom Scale
timeFrame: Baseline, Week 3 and Week 6
measure: Change in Interstitial Cystitis/ Bladder Pain Syndrome (IC/BPS) scores, as measured by the Global Response Assessment (GRA)
timeFrame: Baseline, Week 3 and Week 6
measure: Change in Urinary Symptom scores, as measured by 3-day voiding diaries - Number of Urine Voids
timeFrame: Baseline, Week 3 and Week 6
measure: Change in Urinary Symptom scores, as measured by 3-day voiding diaries - Mean change in Total Volume of Voided Urine
timeFrame: Baseline, Week 3 and Week 6
measure: Change in Urinary Symptom scores, as measured by 3-day voiding diaries - Change in numeric rating scales (NRS) scores
timeFrame: Baseline, Week 3 and Week 6
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Stephen J Walker, PhD
role: PRINCIPAL_INVESTIGATOR
References: