Interstitial CystitisNCT02517996
Use of Preemptive Pudendal Nerve Block Prior to Hydrodistention for the Treatment of Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS)
A study testing Lidocaine in people with Interstitial Cystitis and Painful Bladder Syndrome, run by Johns Hopkins University at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Interstitial Cystitis, Painful Bladder Syndrome
- What is being tested?
- Lidocaine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2015to Jun 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Greater Baltimore Medical Center
Baltimore, Maryland, 21204
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
About this study
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
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.
Read the 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.
- Conditions
- Interstitial Cystitis, Painful Bladder Syndrome
- Being tested
- Lidocaine, Placebo
- Medical subject headings
- Cystitis, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LidocaineDrug
Total 20cc (10cc bilateral) of 1% Lidocaine: Lidocaine is a commonly used anesthetic agent suitable for infiltration, block and surface anesthesia. It is characterized by a rapid onset of action, intermediate duration of efficacy, and its elimination half-life is 90-120 minutes. Lidocaine alters signal conduction in neurons by blocking the fast voltage gated sodium (Na) channels in the neuronal cell membrane that are responsible for signal propagation. With sufficient blockage the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an action potential. This creates the anesthetic effect by not merely preventing pain signals from propagating to the brain but by stopping them before they begin. Adverse drug reactions are rare when lidocaine is used as a local anesthetic and when administered correctly.
PlaceboDrug
Also called Normal Saline
Patients randomized in this arm will receive preemptive bilateral pudendal nerve block with 20 cubic centimeters normal saline after anesthesia induction.
| Study group | Role | What they receive |
|---|---|---|
| 1% Lidocaine | Experimental | Patients randomized in this arm will receive preemptive bilateral pudendal nerve block with 20 cubic centimeters 1% lidocaine after anesthesia induction. Receives: Drug: Lidocaine |
| Normal Saline | Placebo comparator | Patients randomized in this arm will receive preemptive bilateral pudendal nerve block with 20 cubic centimeters normal saline after anesthesia induction. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pain Level as Assessed by the Visual Analog Scale (VAS)
To determine the change in pain at 2 hours, 2 weeks, 6 weeks, and 3 months postoperatively in patients undergoing hydrodistention with preemptive pudendal nerve block (1% Lidocaine) compared to hydrodistention with placebo (saline) using the visual analog scale (VAS).
VAS consists of a 10cm horizontal line with the minimum endpoint labeled "no pain" (0) and maximum labeled "worst pain ever" (10). Patients placed a mark on the point that corresponds to the level of pain severity they felt. The cm distance from the low end of the VAS to the patient's mark is used as the numerical index of the intensity of pain. Pain scores of 3.0-5.4 cm are moderate, over 5.4 indicates severe pain.
Measured: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)
Change in IC Symptom Index Questionnaire With Preemptive Pudendal Nerve Block Compared to Saline
To determine the change in interstitial cystitis symptom index at baseline, 2 hours, 2 weeks, 6 weeks and 3 months after hydrodistention with preemptive pudendal nerve block (1% Lidocaine) compared to hydrodistention with placebo (saline).
The IC symptom index questionnaire consists of 4 questions on IC symptoms. 2 of the questions have 6 answer choices ranging from 0-never, to 5-almost always. 1 question has 6 answer choices ranging from 0-never to 5-usually. 1 question has 7 answer choices ranging from 0-never to 6-5 or more times. The numerical score for each question are added together, with a minimum score of 0 and a maximum score of 21. A higher score indicates greater severity of IC symptoms.
Measured: Baseline, 2 weeks, 6 weeks, 3 months (Up to 3 months)
Change in Problem Index (O'Leary Sant) With Preemptive Pudendal Nerve Block Compared to Saline
To determine the change in problem index (O'Leary Sant) at baseline, 2 hours, 2 weeks, 6 weeks and 3 months after hydrodistention with preemptive pudendal nerve block (1% Lidocaine) compared to hydrodistention with placebo (saline).
The IC problem index questionnaire consists of 4 questions on how much of a problem a patient's IC symptoms cause them. Each question has 5 answer choices ranging from 0-no problem, to 4-big problem. The numerical score for each question are added together, with a minimum score of 0 and a maximum score of 16. A higher score indicates that IC symptoms cause more problems for the patient.
Measured: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)
Change in Pelvic Urgency, Pain, and Frequency (PUF) Questionnaire With Preemptive Pudendal Nerve Block Compared to Saline
To determine the change in pelvic urgency, pain and frequency (PUF) questionnaire at baseline, 2 hours, 2 weeks, 6 weeks and 3 months after hydrodistention with preemptive pudendal nerve block (1% Lidocaine) compared to hydrodistention with placebo (saline).
The Pelvic Urgency, Pain, and Frequency Patient Symptom Scale asks 11 questions, 7 on PUF symptoms, 4 on how bothersome PUF symptoms are. Symptom questions include 3, 4, or 5 ranked answers, with higher answers indicating more voids, or greater frequency of pain. The bother questions each of 4 ranked answers from 0-never, to 3-always. The symptom score is added, the bother score is added, and then the total score is added. The total PUF score is then reported. The minimum score is 0 and the maximum score is 35, and a higher score indicates greater symptoms and higher bother from pelvic pain and frequency.
Measured: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2015 (estimated)
- Study startFeb 2015
- Primary completionJun 2018
- Study completionJun 2018
Why it stopped: Preliminary results were promising when interim analysis performed but terminated due to primary investigators left recruitment site.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (38)Papers the sponsor has linked to this study.
- Other trials for Interstitial CystitisStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tola Fashokun, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02517996
- Sponsor's protocol ID
- IRB00034476
- Status last verified
- Jul 2019
- First submitted
- 23 Feb 2015
- Last updated
- 24 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, Forrest JB, Gordon B, Gray M, Mayer RD, Newman D, Nyberg L Jr, Payne CK, Wesselmann U, Faraday MM; Interstitial Cystitis Guidelines Panel of the American Urological Association Education and Research, Inc. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011 Jun;185(6):2162-70. doi: 10.1016/j.juro.2011.03.064. Epub 2011 Apr 16.
PubMed 21497847De Groat WC. Nervous control of the urinary bladder of the cat. Brain Res. 1975 Apr 11;87(2-3):201-11. doi: 10.1016/0006-8993(75)90417-5. No abstract available.
PubMed 1125771GARRY RC, ROBERTS TD, TODD JK. Reflexes involving the external urethral sphincter in the cat. J Physiol. 1959 Dec;149(3):653-65. doi: 10.1113/jphysiol.1959.sp006366. No abstract available.
PubMed 13826682Birder L, de Groat W, Mills I, Morrison J, Thor K, Drake M. Neural control of the lower urinary tract: peripheral and spinal mechanisms. Neurourol Urodyn. 2010;29(1):128-39. doi: 10.1002/nau.20837.
PubMed 20025024Kuo YC, Kuo HC. The urodynamic characteristics and prognostic factors of patients with interstitial cystitis/bladder pain syndrome. Int J Clin Pract. 2013 Sep;67(9):863-9. doi: 10.1111/ijcp.12116.
PubMed 23952465Malykhina AP. Neural mechanisms of pelvic organ cross-sensitization. Neuroscience. 2007 Nov 9;149(3):660-72. doi: 10.1016/j.neuroscience.2007.07.053. Epub 2007 Sep 8.
PubMed 17920206Pezzone MA, Liang R, Fraser MO. A model of neural cross-talk and irritation in the pelvis: implications for the overlap of chronic pelvic pain disorders. Gastroenterology. 2005 Jun;128(7):1953-64. doi: 10.1053/j.gastro.2005.03.008.
PubMed 15940629Bruns TM, Weber DJ, Gaunt RA. Microstimulation of afferents in the sacral dorsal root ganglia can evoke reflex bladder activity. Neurourol Urodyn. 2015 Jan;34(1):65-71. doi: 10.1002/nau.22514. Epub 2014 Jan 24.
PubMed 24464833Tai C, Wang J, Wang X, de Groat WC, Roppolo JR. Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats. Neurourol Urodyn. 2007;26(4):570-577. doi: 10.1002/nau.20374.
PubMed 17304521McGee MJ, Grill WM. Selective co-stimulation of pudendal afferents enhances bladder activation and improves voiding efficiency. Neurourol Urodyn. 2014 Nov;33(8):1272-8. doi: 10.1002/nau.22474. Epub 2013 Aug 9.
PubMed 23934615Possover M, Forman A. Voiding Dysfunction Associated with Pudendal Nerve Entrapment. Curr Bladder Dysfunct Rep. 2012 Dec;7(4):281-285. doi: 10.1007/s11884-012-0156-5. Epub 2012 Sep 28.
PubMed 23162676Peters KM, Killinger KA, Boguslawski BM, Boura JA. Chronic pudendal neuromodulation: expanding available treatment options for refractory urologic symptoms. Neurourol Urodyn. 2010 Sep;29(7):1267-71. doi: 10.1002/nau.20823.
PubMed 19787710Wang S, Zhang S, Zhao L. Long-term efficacy of electrical pudendal nerve stimulation for urgency-frequency syndrome in women. Int Urogynecol J. 2014 Mar;25(3):397-402. doi: 10.1007/s00192-013-2223-7. Epub 2013 Oct 3.
PubMed 24091564Rovner E, Propert KJ, Brensinger C, Wein AJ, Foy M, Kirkemo A, Landis JR, Kusek JW, Nyberg LM. Treatments used in women with interstitial cystitis: the interstitial cystitis data base (ICDB) study experience. The Interstitial Cystitis Data Base Study Group. Urology. 2000 Dec 20;56(6):940-5. doi: 10.1016/s0090-4295(00)00845-1.
PubMed 11113737Ottem DP, Teichman JM. What is the value of cystoscopy with hydrodistension for interstitial cystitis? Urology. 2005 Sep;66(3):494-9. doi: 10.1016/j.urology.2005.04.011.
PubMed 16140064
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02517996
- Acronym / sponsor ID
- IRB00034476
- Conditions
- Interstitial Cystitis, Painful Bladder Syndrome
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Preliminary results were promising when interim analysis performed but terminated due to primary investigators left recruitment site.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Feb 2015 (actual)
- Primary completion
- Jun 2018 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 7 Aug 2015 (estimated)
- Results
- Posted 9 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1% Lidocaine | Experimental | Drug: LidocainePatients randomized in this arm will receive preemptive bilateral pudendal nerve block with 20 cubic centimeters 1% lidocaine after anesthesia induction. |
| Normal Saline | Placebo comparator | Drug: PlaceboPatients randomized in this arm will receive preemptive bilateral pudendal nerve block with 20 cubic centimeters normal saline after anesthesia induction. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LidocaineTotal 20cc (10cc bilateral) of 1% Lidocaine: Lidocaine is a commonly used anesthetic agent suitable for infiltration, block and surface anesthesia. It is characterized by a rapid onset of action, intermediate duration of efficacy, and its elimination half-life is 90-120 minutes. Lidocaine alters signal conduction in neurons by blocking the fast voltage gated sodium (Na) channels in the neuronal cell membrane that are responsible for signal propagation. With sufficient blockage the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an action potential. This creates the anesthetic effect by not merely preventing pain signals from propagating to the brain but by stopping them before they begin. Adverse drug reactions are rare when lidocaine is used as a local anesthetic and when administered correctly. | Drug | 1% Lidocaine |
| PlaceboAlso: Normal SalinePatients randomized in this arm will receive preemptive bilateral pudendal nerve block with 20 cubic centimeters normal saline after anesthesia induction. | Drug | Normal Saline |
Primary outcome
Change in Pain Level as Assessed by the Visual Analog Scale (VAS)
Time frame: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)
To determine the change in pain at 2 hours, 2 weeks, 6 weeks, and 3 months postoperatively in patients undergoing hydrodistention with preemptive pudendal nerve block (1% Lidocaine) compared to hydrodistention with placebo (saline) using the visual analog scale (VAS). VAS consists of a 10cm horizontal line with the minimum endpoint labeled "no pain" (0) and maximum labeled "worst pain ever" (10). Patients placed a mark on the point that corresponds to the level of pain severity they felt. The cm distance from the low end of the VAS to the patient's mark is used as the numerical index of the intensity of pain. Pain scores of 3.0-5.4 cm are moderate, over 5.4 indicates severe pain.
Change in IC Symptom Index Questionnaire With Preemptive Pudendal Nerve Block Compared to Saline
Time frame: Baseline, 2 weeks, 6 weeks, 3 months (Up to 3 months)
To determine the change in interstitial cystitis symptom index at baseline, 2 hours, 2 weeks, 6 weeks and 3 months after hydrodistention with preemptive pudendal nerve block (1% Lidocaine) compared to hydrodistention with placebo (saline). The IC symptom index questionnaire consists of 4 questions on IC symptoms. 2 of the questions have 6 answer choices ranging from 0-never, to 5-almost always. 1 question has 6 answer choices ranging from 0-never to 5-usually. 1 question has 7 answer choices ranging from 0-never to 6-5 or more times. The numerical score for each question are added together, with a minimum score of 0 and a maximum score of 21. A higher score indicates greater severity of IC symptoms.
Change in Problem Index (O'Leary Sant) With Preemptive Pudendal Nerve Block Compared to Saline
Time frame: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)
To determine the change in problem index (O'Leary Sant) at baseline, 2 hours, 2 weeks, 6 weeks and 3 months after hydrodistention with preemptive pudendal nerve block (1% Lidocaine) compared to hydrodistention with placebo (saline). The IC problem index questionnaire consists of 4 questions on how much of a problem a patient's IC symptoms cause them. Each question has 5 answer choices ranging from 0-no problem, to 4-big problem. The numerical score for each question are added together, with a minimum score of 0 and a maximum score of 16. A higher score indicates that IC symptoms cause more problems for the patient.
Change in Pelvic Urgency, Pain, and Frequency (PUF) Questionnaire With Preemptive Pudendal Nerve Block Compared to Saline
Time frame: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)
To determine the change in pelvic urgency, pain and frequency (PUF) questionnaire at baseline, 2 hours, 2 weeks, 6 weeks and 3 months after hydrodistention with preemptive pudendal nerve block (1% Lidocaine) compared to hydrodistention with placebo (saline). The Pelvic Urgency, Pain, and Frequency Patient Symptom Scale asks 11 questions, 7 on PUF symptoms, 4 on how bothersome PUF symptoms are. Symptom questions include 3, 4, or 5 ranked answers, with higher answers indicating more voids, or greater frequency of pain. The bother questions each of 4 ranked answers from 0-never, to 3-always. The symptom score is added, the bother score is added, and then the total score is added. The total PUF score is then reported. The minimum score is 0 and the maximum score is 35, and a higher score indicates greater symptoms and higher bother from pelvic pain and frequency.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21497847Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, Forrest JB, Gordon B, Gray M, Mayer RD, Newman D, Nyberg L Jr, Payne CK, Wesselmann U, Faraday MM; Interstitial Cystitis Guidelines Panel of the American Urological Association Education and Research, Inc. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011 Jun;185(6):2162-70. doi: 10.1016/j.juro.2011.03.064. Epub 2011 Apr 16.
- Background: PubMed 1125771De Groat WC. Nervous control of the urinary bladder of the cat. Brain Res. 1975 Apr 11;87(2-3):201-11. doi: 10.1016/0006-8993(75)90417-5. No abstract available.
- Background: PubMed 13826682GARRY RC, ROBERTS TD, TODD JK. Reflexes involving the external urethral sphincter in the cat. J Physiol. 1959 Dec;149(3):653-65. doi: 10.1113/jphysiol.1959.sp006366. No abstract available.
- Background: PubMed 20025024Birder L, de Groat W, Mills I, Morrison J, Thor K, Drake M. Neural control of the lower urinary tract: peripheral and spinal mechanisms. Neurourol Urodyn. 2010;29(1):128-39. doi: 10.1002/nau.20837.
- Background: PubMed 23952465Kuo YC, Kuo HC. The urodynamic characteristics and prognostic factors of patients with interstitial cystitis/bladder pain syndrome. Int J Clin Pract. 2013 Sep;67(9):863-9. doi: 10.1111/ijcp.12116.
- Background: PubMed 17920206Malykhina AP. Neural mechanisms of pelvic organ cross-sensitization. Neuroscience. 2007 Nov 9;149(3):660-72. doi: 10.1016/j.neuroscience.2007.07.053. Epub 2007 Sep 8.
- Background: PubMed 15940629Pezzone MA, Liang R, Fraser MO. A model of neural cross-talk and irritation in the pelvis: implications for the overlap of chronic pelvic pain disorders. Gastroenterology. 2005 Jun;128(7):1953-64. doi: 10.1053/j.gastro.2005.03.008.
- Background: PubMed 24464833Bruns TM, Weber DJ, Gaunt RA. Microstimulation of afferents in the sacral dorsal root ganglia can evoke reflex bladder activity. Neurourol Urodyn. 2015 Jan;34(1):65-71. doi: 10.1002/nau.22514. Epub 2014 Jan 24.
- Background: PubMed 17304521Tai C, Wang J, Wang X, de Groat WC, Roppolo JR. Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats. Neurourol Urodyn. 2007;26(4):570-577. doi: 10.1002/nau.20374.
- Background: PubMed 23934615McGee MJ, Grill WM. Selective co-stimulation of pudendal afferents enhances bladder activation and improves voiding efficiency. Neurourol Urodyn. 2014 Nov;33(8):1272-8. doi: 10.1002/nau.22474. Epub 2013 Aug 9.
- Background: PubMed 23162676Possover M, Forman A. Voiding Dysfunction Associated with Pudendal Nerve Entrapment. Curr Bladder Dysfunct Rep. 2012 Dec;7(4):281-285. doi: 10.1007/s11884-012-0156-5. Epub 2012 Sep 28.
- Background: PubMed 19787710Peters KM, Killinger KA, Boguslawski BM, Boura JA. Chronic pudendal neuromodulation: expanding available treatment options for refractory urologic symptoms. Neurourol Urodyn. 2010 Sep;29(7):1267-71. doi: 10.1002/nau.20823.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tola Fashokun, M.D. principal investigator
Johns Hopkins University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lidocaine in people with Interstitial Cystitis and Painful Bladder Syndrome, run by Johns Hopkins University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pain Level as Assessed by the Visual Analog Scale (VAS) (time frame: Baseline, 2 hours, 2 weeks, 6 weeks, 3 months (Up to 3 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02517996, which also lists 38 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2019.