Acupuncture for Female IC/PBSyndrome and Its Effect on the Urinary Microbiome: A Randomized Controlled Trial

Study Overview
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Brief Summary
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The investigators central hypothesis is that women with Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) will benefit from acupuncture compared with sham treatment and acupuncture responders will have a differential urinary microbiome.

Detailed Description
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The Urinary Microbiota. Within internal surfaces, which are defined as existing outside the body (e.g. the intestinal epithelium or the vaginal epithelium), there exist commensal microbial communities. These microbiota are believed to be beneficial to human health, facilitating efficient removal of improperly functioning immune cells and protecting the host from pathogen infection13-15. The human bladder is a core component of the human urinary tract. It is a hollow muscular organ lined with transitional epithelium, which functions as the storage site for metabolic wastes in the form of urine. Given that the bladder's luminal space is also considered outside the body, it would seem reasonable that a urinary microbiota would be present. Yet, the historic dogma has maintained that urine is sterile, based on culture-dependent methods of bacterial detection. This paradigm is shifting, however, based on our newly published data noting the presence of a urinary microbiota in adult women without clinical urinary tract infections16,17. Furthermore, we have recently discovered that the microbiota of women with overactive bladder (specifically with associated urgency incontinence) is distinguishable from the microbiota of women with stress urinary incontinence. These findings suggest that IC/PBS may be influenced by an alteration to the urinary microbiota. Indeed, recent evidence reports a difference in the urinary microbiome dominated by Lactobacillus in subjects with IC/PBS compared with healthy controls18. This work is limited by lack of correlative clinical symptomatology, small sample size and urinary samples that may have been contaminated. The investigators long term goal is to determine pelvic pain mechanisms that will inform clinically-relevant classification and evidence-based treatment of women with IC/PBS and CPP. The short term goal of this application is to determine the safety, tolerability and efficacy of acupuncture in women with IC/PBS as a neuromodulative treatment and to correlate the urinary microbiome with acupuncture responders. Our approach will advance the understanding of the contribution and consequences of peripheral pelvic nociception in IC/PBS.

Official Title
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Acupuncture for Female Interstitial Cystitis/Painful Bladder Syndrome and Its Effect on the Urinary Microbiome: A Randomized Controlled Trial

Conditions
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Painful Bladder Syndrome, Interstitial Cystitis

Intervention / Treatment
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* Device: standard acupuncture treatment
* Device: Control Sham/Minimal Acupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females, age 21 to 65 years Symptoms of urinary frequency, urgency and suprapubic/bladder pain for > 6 months Generally stable health An average bladder pain score of at least >3/10 Exclusion Criteria: Patients with pacemaker or other neurostimulator (gastric/spinal) History or current symptomatic urethral stricture, cystitis caused by tuberculosis, radiation therapy or Cytoxan/cyclophosphamide therapy Prior augmentation cystoplasty or cystectomy Systemic autoimmune disorder (such as Crohn's Disease, Ulcerative Colitis, Lupus, Rheumatoid Arthritis, or Multiple Sclerosis) Systemic neuromuscular disease known to affect the lower urinary tract History of urogenital cancer (with the exception of minor skin cancer) Current or imminent planned pregnancy/recent delivery <6 months Current pelvic floor physical therapy Current use of opioid medications (short or long acting) for pain Abdominal or pelvic surgery within the last 6 months.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Minimal Acupuncture<br>Fifteen (15) will be allocated in the control sham/minimal acupuncture + standard medical treatments of IC. The sham intervention (also described as minimal intervention) will use superficial needle insertion at body locations not recognized as true acupoints. Patients will be explained that various acupuncture treatment protocols will be tested including minimal acupuncture, therefore, the control group will not be aware of receiving sham acupuncture. | Device: Control Sham/Minimal Acupuncture<br>* Control group will receive sham/minimal acupuncture with low level electrical stimulation. The sham intervention (also described as minimal intervention) will use superficial needle insertion at body locations not recognized as true acupoints. Patients will be explained that various acupuncture treatment protocols will be tested including minimal acupuncture, therefore, the control group will not be aware of receiving sham acupuncture. These described acupuncture treatments are well accepted treatment protocols for women with pelvic pain and bladder complaints.<br>|
| Active Comparator: Standard acupuncture treatment<br>Fifteen (15) will be allocated in the standard acupuncture treatment + medical management of IC. Standard acupuncture treatment protocol will include 4 gates plus GV 20 to reduce anxiety and help with relaxation and to assess acupuncture naïve patient's response to needles during their first acupuncture encounter. Subsequent visits would include administration of curious meridian Chong Mo paired with Yang Ming. 4 Hz low level electrical stimulation will be applied. | Device: standard acupuncture treatment<br>* A standardized acupuncture treatment will be assigned, and both groups will receive 7 acupuncture treatments that follow a standardized protocol on classical acupuncture points, with or without mild electrical stimulation versus sham/minimal acupuncture. Acupuncture needles are single use, sterile and disposable. Standard acupuncture treatment protocol will include 4 gates plus GV 20 to reduce anxiety and help with relaxation and to assess acupuncture naïve patient's response to needles during their first acupuncture encounter. Subsequent visits would include administration of curious meridian Chong Mo paired with Yang Ming. 4 Hz low level electrical stimulation will be applied.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Acupuncture to Reduce Pain in Women With Interstitial Cystitis/Painful Bladder Syndrome | Change in worst pain as measured by the Brief Pain Inventory-Short Form. Scores range from 0 to 10 and higher scores indicate more pain. Change is calculated as the 6 weeks score minus the baseline score. | 0 weeks, 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of Acupuncture in Women With Interstitial Cystitis/Painful Bladder Syndrom | The total number of acupuncture sessions stopped due to poor tolerability of acupuncture | 0 weeks, 6 weeks | 
| Safety of Acupuncture in Women With Interstitial Cystitis/Painful Bladder Syndrome | The total number of adverse events experienced by women receiving acupuncture | 0 weeks, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Painful Bladder Syndrome, Interstitial Cystitis, Suprapubic Pain, Urinary Urgency