Clinical trial NCT02517996: Use of Preemptive Pudendal Nerve Block Prior to Hydrodistention for the Treatment of Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS)
Official title: Use of Preemptive Pudendal Nerve Block Prior to Hydrodistension for the Treatment of Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS): a Prospective, Double-blinded, Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Interstitial Cystitis
Painful Bladder Syndrome
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2015-08-07
Enrollment: 18
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/Painful bladder syndrome (IC/PBS) is a chronic debilitating condition that severely impacts between 2.7 and 6.5 percent of women in the United States. Despite its public health importance the pathogenesis of IC/PBS is not well understood and there is no consensus on the optimal treatment approach for this condition. Hydrodistention is the most commonly used therapy for this condition; but it is limited by severe immediate postoperative bladder pain and its short duration of action. It has been postulated that hydrodistention works by disrupting the sensory nerves within the bladder that may be contributing to bladder pain. Recent evidence has provided support for the use of preemptive pudendal nerve block as a way to blunt immediate postoperative pain. The investigators hypothesize that preemptive pudendal nerve block prior to hydrodistention will result in lower postoperative pain after hydrodistention compared to placebo. This is a prospective double- blinded randomized study and patients will be randomized to receive preemptive bilateral pudendal nerve block with either 1% lidocaine or placebo. Bladder pain will be compared at baseline, 2 hours, 2 weeks, 6 weeks and 3 months using the Visual Analog Scale, O'Leary-Sant questionnaire and the Pelvic Pain Urgency and Frequency questionnaire.

Detailed description: Painful bladder syndrome/interstitial cystitis (IC/PBS) is a disorder characterized by chronic bladder pain or discomfort. The exact underlying etiology of IC/PBS is unknown however several theories exist which include epithelial dysfunction, mast cell activation, and neurogenic inflammation. Whatever the underlying inciting factor for IC/PBS, the resulting phenotype is one of urinary frequency, urgency and bladder pain improved after voiding. Animal studies show that as the normal bladder fills, mechanoreceptors in the bladder wall respond to stretch through the discharge of afferent innervations or nerve firing. In normal humans, there is no conscious perception that the bladder is filling until a threshold volume is reached4. Patients with PBS/IC are thought to have substantially lower cystometric bladder volumes and a heightened sensitivity to bladder filling. Mechanoreceptors and chemoreceptors in the bladder may trigger myelinated A- delta or C-fibers found in the smooth muscle or in the submucosa in response to bladder distention. A- delta fibers are distributed mainly within the detrusor smooth muscle and are responsive to detrusor stretch that occurs during bladder filling. In contrast, C-type fibers seem to be more widespread and are distributed in the detrusor muscle, within the lamina propria and in close proximity to the urothelium. There is considerable interest in mechanisms underlying sensitization of C-fiber afferents, as these nerves are thought to play a key role in symptoms of IC/PBS. It has been shown that the plexus of afferent nerves is most dense in the regions of the bladder neck and proximal urethra. Lumbosacral afferent fibers in the pelvic and pudendal nerve, with cell bodies in the lumbosacral dorsal root ganglion (DRG), not only sense pain but also regulate continence and micturition. In laboratory animals, the pelvic nerve supply contains more stretch-responsive afferent fibers and appears to be important in responses to bladder over-distention. Neurologic changes seen after the occurrence of cystitis or other bladder insult suggest reorganization of reflex connections in the spinal cord and changes to the bladder afferents, that may suggest a greater role for the influence of the pudendal nerve on bladder pain than had been previously thought.

The pudendal nerve is a peripheral nerve that is mainly composed of afferent sensory fibers from sacral nerve roots S1, S2, and S3 and consequently it is a major contributor to bladder afferent regulation and bladder function. Pudendal nerve entrapment often leads to significant voiding dysfunction including urinary incontinence and over active bladder syndrome Furthermore, because the pudendal nerve carries such a large percentage of afferent fibers, it has been an attractive target for neuromodulation in treating refractory overactive bladder and may be useful for modulating pain experienced in IC/PBS.

No treatment has been consistently shown to provide relief in the majority of patients with painful bladder syndrome. Furthermore, combination treatment modalities are needed in the majority of patients. Cystoscopy with hydrodistention is thought to be a useful therapeutic tool in patients who are unresponsive to therapies like medication and pelvic floor physical therapy; however, its use has only been studied in a few observational studies and is currently listed as a third line treatment option for IC/PBS. According to the interstitial cystitis database study experience cystoscopy with hydrodistention is reported to be the most commonly used treatment modality for IC/PBS and published studies have reported improvement in symptoms in 70 to 80 percent of patients while other studies have reported improvement in only 40 percent. It has been postulated that hydrodistention works by disrupting the sensory nerves within the bladder that may be contributing to bladder pain and enabling the regeneration of afferent sensory nerves. Though the exact mechanism of action is unclear, there is ample evidence to suggest the efficacy of cystoscopy with hydrodistention, in a recent study by Chien-Ying et al, therapeutic hydrodistension was associated with an increase in bladder capacity and significant reduction in average O'Leary- Sant symptom and problem scores after treatment. In addition, Aihara et al who determined a positive therapeutic outcome in 71% of patients 1 month after hydrodistention have reported similar findings. The disadvantages of hydrodistention are that some patients experience a temporary worsening of their symptoms immediately following the procedure and any beneficial effect often lasts between 2-6 weeks. The immediate worsening of bladder symptoms immediately after hydrodistention and its relatively short duration of effect are often deterrents to recommending this therapy to patients. Given the multimodal approach to managing patients with IC/PBS it is imperative that the investigators explore ways to prolong the efficacy of available options and one approach that has been recently suggested is the use of preemptive analgesia.

In 1983, Woolf proposed that persistent pain experienced after trauma or surgery is due to posttraumatic functional changes not only in the peripheral pain receptors but also in the dorsal horn of the spinal cord a property known as hyperexcitability. The hyperexcitable state persists long after such stimuli cease, causing the patient to perceive pain from stimuli normally believed to be painless a common occurrence thought to be seen in patients with IC/PBS. Therefore, prevention of spinal hyperexcitability by blockade of the afferent nerve pathway from surgical site to spinal cord may therefore decrease the amount and duration of postoperative pain perception. This theory has been tested in various animal studies and was first described by Wall in 1988. In addition, the current literature on preemptive analgesia in gynecology is supportive of this approach. In a study by Ismail et al, 130 patients undergoing posterior colporrhaphy were randomized to receive preemptive pudendal nerve block with either .25% bupivacaine or normal saline. Study findings demonstrated an average postoperative Visual Analog Scale (VAS) score of 51.1 for the bupivacaine group compared to 23.5 in the placebo group. The investigators postulate that since the pudendal nerve is an important contributor to bladder afferent regulation, preemptive nerve block prior to hydrodistention may block afferent impulse transmission to the spinal cord and decrease the initial increase in postoperative bladder pain.

Eligibility criteria: Inclusion Criteria:

* All women aged greater than 18 years of age scheduled to undergo cystoscopy with hydrodistention
* who are literate,
* English speaking and
* can provide written informed consent will be included in this study.

Exclusion Criteria:

* Patients who have intolerance or known allergies to local analgesia will be excluded.
* In addition, patients who have coagulation disorders will also be excluded as this may increase their risks of complication from bleeding.
* Patient will also be excluded if they have a history of dementia as this may impair their ability to follow instructions.
* Patients who are non-ambulatory and who have an inability to fully assess pain will also be excluded.
* Patients receiving additional surgical procedures will be excluded from the study, as the source of their pain may be difficult to decipher in the immediate post-operative period.

Primary outcomes:
measure: Change in Pain Level as Assessed by the Visual Analog Scale (VAS)
timeFrame: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)
measure: Change in IC Symptom Index Questionnaire With Preemptive Pudendal Nerve Block Compared to Saline
timeFrame: Baseline, 2 weeks, 6 weeks, 3 months (Up to 3 months)
measure: Change in Problem Index (O'Leary Sant) With Preemptive Pudendal Nerve Block Compared to Saline
timeFrame: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)
measure: Change in Pelvic Urgency, Pain, and Frequency (PUF) Questionnaire With Preemptive Pudendal Nerve Block Compared to Saline
timeFrame: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Tola Fashokun, M.D.
role: PRINCIPAL_INVESTIGATOR
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