Sacral Neuromodulation for Chronic Pelvic Pain

Study Overview
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Brief Summary
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Sacral neuromodulation (SNM) is a safe, effective, and minimally invasive FDA approved treatment for urinary and fecal incontinence, urinary frequency, urgency, and urinary retention. In this study we are assessing the effectiveness of sacral neuromodulation in women with suffering from chronic pelvic pain (CPP), through a single device implant procedure.

Detailed Description
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Despite SNM being available for more than 25 years, there are many things about this technology that remain elusive. Enhancing our understanding of SNM in the chronic pelvic pain (CPP) population can rapidly improve the care of current patients suffering from pelvic pain, as well as help develop future technologies, stimulation paradigms, and lead to effective counseling of patients. CPP is one of most common and challenging conditions for clinicians to treat today. CPP is defined as nonmalignant persistent pain perceived in structures or organs of the pelvis for at least 6 months. As such, CPP can be caused by numerous underlying conditions from gynecological (e.g. endometriosis), gastrointestinal (e.g. celiac disease, irritable bowel syndrome), urological (e.g. interstitial cystitis), musculoskeletal (e.g. fibromyalgia), prostatitis, and neurological/vascular (e.g. spinal cord injury, ilioinguinal nerve entrapment) origin. From a urological perspective, the pain in CPP syndrome can be associated with symptoms suggesting urinary, sexual or bowel dysfunction, and are commonly associated with Overactive Bladder (OAB) symptoms of urinary frequency, urgency, and incontinence. CPP has a debilitating effect on quality of life, leading to other comorbidities such as depression, anxiety, and sleep disorders. CPP is common in both men and women, but occurs more frequently in women. This study will assess the effectiveness of sacral neuromodulation in women. This is a prospective single arm and single blinded quasi-placebo controlled study. Patients will be blinded to the device settings. For those that qualify, the sacral neuromodulation device will be placed by an experienced physician. After placement in the operating room the device settings will be adjusted. 2 weeks post-operatively participants return and complete study questionnaires. The devices settings will again be adjusted at this visit. The device may turned on/off, or settings modified throughout the study. To maintain study integrity, patients will not be informed how device settings are changed. At each follow up visit, participants will be asked to complete study questionnaires and will have their device settings adjusted. Participants will follow up over a course of 12 months from the time of device implantation.

Official Title
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Sacral Neuromodulation for the Treatment of Chronic Pelvic Pain

Conditions
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Chronic Pelvic Pain Syndrome

Intervention / Treatment
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* Device: Sacral neuromodulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Female, aged 22-70 Failed a t least 1 or more conservative treatments (e.g. pelvic floor physical therapy, biofeedback, behavioral modification, oral pharmacotherapy, bladder instillations) No changes to current regimen of medications for their pelvic pain for > 4 weeks prior to screening For females of reproductive potential: use of highly effective contraception (e.g. licensed hormonal or barrier methods), for at least 1 month prior to screening and agreement to use such a method during study participation Exclusion Criteria: History of any pelvic cancer Any significant medical condition that is likely to interfere with study procedures, device operation, or likely to confound evaluation of study endpoints Concurrent pain management strategies that may interfere or mask study intervention (e.g. pelvic floor physical therapy, shockwave therapy, trigger point injections, bladder instillations) Any psychiatric or personality disorder at the discretion of the study physician. This does not include depression or generalized anxiety disorders that are stable. Current symptomatic urinary tract infection (UTI) or more than 3 UTIs in past year Severe or uncontrolled diabetes (A1C > 7, documented in the last 3 months) or diabetes with peripheral nerve involvement Interstitial cystitis diagnosis with Hunner's lesions as this is a severe inflammatory bladder condition that can only be treated with eradication of the lesions or a cystectomy. SNM would be be expected to help for IC with Hunner's lesions Previously implanted with a sacral neuromodulation device or participated in a sacral neuromodulation trial Subject with documented history of allergy to titanium, zirconia, polyurethane, epoxy, or silicone Implantation of spinal cord stimulator and/or drug delivery pumps, whether turned on or off A female who is breastfeeding or of child-bearing potential with a positive urine pregnancy test or not using adequate contraception Current treatment for active malignancy (skin cancers excluded) Patients with spinal pathology that could confound study results. This may include participants with cauda equina syndrome, spinal stenosis, neurogenic claudication, lumbar radiculopathy, patients with primary complaints of leg pain with numbness and or weakness, patients with a primary pain compliant that is vascular in origin, clinical evidence of progressive neurologic pathology, mechanical instability or other spinal pathology that requires surgical intervention, spine or visceral pain secondary to neoplasm, visceral pain in the upper abdomen rather than the pelvis, current diagnosis of fibromyalgia participants with significant cognitive impairment, participants with a condition currently requiring or likely to require use of diathermy or MRI. Participants involved in ongoing litigation and or injury claims or workers compensation claims. Participation in a current clinical trial or within the preceding 30 days Note- to preserve the scientific integrity of the study some criteria have been omitted from this posting. All eligibility criteria will be listed at the close of the study.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 70 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
Intervention Model: Sequential Assignment
Interventional Model Description: Single arm and participant-blinded sequential treatment controlled clinical trial. The device will be turned on or off, and settings adjusted at each visit. To minimize bias throughout the study, patients will be blinded to the device settings; however, since there is only one arm, open label has been chosen below.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SNM for the treatment of CPP<br>Patients will be enrolled based on study eligibility criteria. Eligible patients will be scheduled for a Interstim X implant in the operating room. The procedure is completed under anesthesia, either conscious sedation with intubation or breathing assistance. Under fluoroscopic guidance a standard lead will be introduced. Each electrode on the lead will be tested by confirming motor response on at least 3 of 4 leads. Next the implantable pulse generator will be placed in a subcutaneous pocket and secured. Impedance will be tested, 4 standard programs will be set, and then the device will be shut off. The device settings will be adjusted per protocol and the device will be turned on and off during visits 2-7. | Device: Sacral neuromodulation<br>* Interstim X, which includes an implantable pulse generator and lead, will be implanted surgically in a single-stage procedure.<br>* Other names: Interstim X;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in pain score using a 10-point Visual Analogue Scale (VAS) from 2-10 weeks. | The VAS is a validated tool to determine patient perceived pain. VAS is scored from 0-10, where 0 = no pain and 10 = worst possible pain. The value at Visit 4 (10 weeks post-implant) minus the value at Visit 2 (baseline, 2 weeks post-implant) will be used to calculate change. Negative numbers indicate an improvement in pain, and positive numbers indicate a worsening pain | Visit 2 (2 weeks post-implant) and Visit 4 (10 weeks post-implant) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in central sensitization score over 13 months | Change in central sensitization will be assessed using the temporal summation test using the TSA2 AIR system. Temporal summation is considered a manifestation of central sensitization and can be assessed using thermal modalities. It is measured as the magnitude of positive slope of the line fitted to the series of 10 stimuli at the target temperature. A larger slope reflects a higher degree of central sensitization. The central sensitization slope at each treatment visit (visits 3 through 8) minus the slope at visit 2 (baseline, 2 weeks post-implementation) will be recorded and analyzed. A positive number reflects more central sensitization, and a negative number reflects less central sensitization. | Visit 2 (2 weeks post-implant) through Visit 8 (an average of 13 months post-implant) | 
| Change in pelvic floor pain using a 10-point VAS pain score. | A trained provider will palpate all 4 quadrants of the pelvis, while recording pain scores for each quadrant. The VAS is a validated questionnaire that assesses pain on a scale from 0 = no pain to 10 = worst possible pain. The subject will provide a pain score from 0 - 10 for each of the 4 quadrants assessed. The average pain score of the 4 quadrants is then calculated. The average pain score ranges from 0 to 10. The difference in value from visit 2 (baseline, 2 weeks post implant) minus visit 8 (an average of 13 months post implant) is calculated. A positive number indicates improvement of symptoms. A negative number indicates worsening of symptoms. | Visit 2 (2 weeks post-implant) through Visit 8 (an average of 13 months post-implant) | 
| Change in severity of overactive bladder symptoms. | The change in OAB symptoms between baseline (visit 2) and subsequent study visits will be assessed using the 6-question Overactive Bladder Questionnaire Short Form (OABq). OABq is a well-established questionnaire used to assess severity of OAB symptoms. The OAB-Q Short Form (SF) consists of two scales assessing symptom bother and health-related quality of life (HR-QOL) in patients with OAB. Each question is rated on a 6 point scale with 1 = Not at all and 6 = A very great deal. Scores can range from 0 to 100, with higher scores indicating more severe symptoms. The change is calculated from the baseline (visit 2, 2 weeks post-implant) minus the value at visit 8 (an average of 13 months post-implant). A positive number indicates improvement of symptoms. A negative number indicates worsening of symptoms. | Visit 2 (2 weeks post-implant) and Visit 8 (an average of 13 months post-implant) | 
| Change in Female Sexual Function | The Female Sexual Function Index (FSFI) is a 19-question questionnaire evaluating female sexual health in several domains: libido, arousal, lubrication, orgasm, satisfaction, and sexual pain. Each subdomain is scored separately, and the total score calculated. Change in FSFI score will be assessed between baseline (visit 2, 2 weeks-post implant) and visit 8 (an average of 13 months post-implant). A lower FSFI score is equivalent to a higher degree of sexual dysfunction. Scores range from 0 to 36. The change value is calculated from visit 8 (approximately 13 months post-implant) minus visit 2 (baseline, 2 weeks post-implant). A positive number indicates improvement of symptoms. A negative number indicates worsening of symptoms. | Visit 2 (2 weeks post-implant) and Visit 8 (an average of 13 months post-implant) | 
| Change in mental health and anxiety. | The Pain Catastrophizing Scale (PCS) is used to determine the impact of SNM on mental health related to pain. Pain catastrophizing is the tendency to describe a pain experience in more exaggerated terms than the average person. The PCS is a validated measure of rumination, magnification, and helplessness related to pain. The PCS has been shown to have adequate to excellent internal consistency. People with higher PCS scores have a tendency to be more likely to report their pain as intense than those with low PCS scores. This objective will be measured at visit 4 (10 weeks post-implant), visit 5 (an average of 11-15 weeks post-implant), visit 7 (12 months post-implant) and visit 8 (an average of 13 months post-implant) and compared to visit 2 scores (baseline, 2 weeks post-implant). Each value will be subtracted from baseline and the difference will be reported. A negative number will indicate more pain catastrophizing, and a positive number will indicate less pain catastrophizing. | Visit 2 (2 weeks post-implant), Visit 4 (10 weeks post-implant), Visit 5 (an average of 11-15 weeks post-implant), Visit 7 (12 months post-implant), and Visit 8 (an average of 13 months post-implant) | 
| Patient satisfaction with sacral neuromodulation treatment | Patient satisfaction will be assessed using the Global Response Assessment (GRA) tool on which the patient rates overall patient-perceived symptom improvement on a 7-point scale at visit 4 (10 weeks post-implant) through visit 8 (an average of 13 months post-implant). It is scored as follows: 1 = markedly worse, 2 = moderately worse, 3 = mildly worse, 4 = same (unchanged), 5 = slightly improved, 6 = moderately improved, and 7 = markedly improved. Significant improvement is considered those patient rating their symptoms to be moderately to markedly improved. | Visit 4 (10 weeks post-implant), Visit 5 (an average of 11-15 weeks post-implant), Visit 7 (12 months post-implant), and Visit 8 (an average of 13 months post-implant) | 
| Treatment durability measured as change in pain scores from baseline (visit 2) to visit 7 (12 months post-implant) as measured by 10-point visual-analog scale. | Treatment durability will be assessed using the 10-point Visual Analogue Scale (VAS) for pain. VAS is scored from 0-10, where 0 = no pain and 10 = worst possible pain. The value at Visit 7 (12 months post-implant) minus the value at Visit 2 (baseline, 2 weeks post-implant) will be used to calculate change. Negative numbers indicate an improvement in pain, and positive numbers indicate a worsening pain | Visit 2 (2 weeks post-implant) and Visit 7 (12 months post-implant) | 
| Number of days of carry-over effect after short and long treatment (an average of 13 months post implant) | This objective will be assessed by counting the number of days after visit 7 (12 months post-implant) until the patient reports pain scores that are same (or worse) than reported at visit 2 (baseline, 2 weeks post-implant). This will indicate how long the treatment effect lasts after treatment has been discontinued. | Visit 8 (an average of 13 months post-implant) | 
| Safety and tolerability: number of adverse events related to the device implantation. | Safety and tolerability of sacral neuromodulation in chronic pelvic pain patients will be assessed by recording the number of adverse events that are determined to be related to device implantation. Adverse events will be assessed at each scheduled study visit or as reported by patients outside study visits. | Visit 2 (2 weeks post-implant) through Visit 8 (an average of 13 months post-implant) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Women