PTNS for Female Patients Suffering From Multiple Sclerosis

Study Overview
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Brief Summary
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This is a pilot, single blind, randomized, sham-controlled trial to assess the benefit of PTNS in treating OAB symptoms in MS patients. The data generated by this study would provide support for a future multi-institutional, randomized prospective trial.

Detailed Description
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Multiple Sclerosis (MS) is a chronic, progressive inflammatory disorder of the central nervous system. It is caused by loss of myelin, the outer protective layer of the neuron, resulting in a disruption of the signal potentials that flow through the neurons. This can lead to a variety of sensory, visual, and motor disturbances. MS affects almost 1 million people in the United States with the prevalence being two to three times higher in women than in men. Over 80% of MS patients suffer from lower urinary tract symptoms, with bladder overactivity (OAB) and urinary incontinence (UI) being the predominant bladder dysfunctions. OAB is characterized by sudden feeling of urgency, frequent urination, and urge incontinence. Percutaneous Tibial Nerve Stimulation (PTNS) is an FDA approved treatment for OAB and is recommended as third line treatment for OAB by the American Urological Association (AUA) and Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU). However, it is not approved for MS and as such these treatments are not covered by insurance. Here the investigators propose a pilot, double blind, randomized, sham-controlled trial to assess the benefit of PTNS in treating OAB symptoms in MS patients. The data generated by this study would provide support for a future multi-institutional, randomized prospective trial.

Official Title
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Percutaneous Tibial Nerve Stimulation (PTNS) Therapy for Female Patients Suffering From Multiple Sclerosis

Conditions
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Multiple Sclerosis, Overactive Bladder

Intervention / Treatment
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* Device: PTNS Treatment
* Device: Sham PTNS Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with diagnosis for Multiple Sclerosis (CIS, RRMS, SPMS, and/or PPMS), 18 years of age or older Self-reported bladder symptoms > 3 months Discontinued antimuscarinics/beta-3 agonists for > 2 weeks, and remain off for the duration of the study Capable of giving informed consent Ambulatory and able to use toilet independently without difficulty Capable and willing to follow all study-related procedures If of childbearing age, agree to practice approved birth-control methods (oral contraceptives, condom barrier, injection, diaphragm or cervical cap, vaginal contraceptive ring, IUD, implantable contraceptive, surgical sterilization (bilateral tubal ligation), vasectomized partner(s)) Subject agrees not to start any new treatments for urinary symptoms (medication or otherwise) during the treatment and follow-up periods. Subject agrees to maintain a stable dose on all current medications throughout the treatment and follow-up period. Exclusion Criteria: Pregnant or planning to become pregnant during study duration BTX use in bladder or pelvic floor muscles within past 6 months Pacemakers or implantable defibrillators Current urinary tract infection Active use of neuromodulation in any other form. If patient has InterStim, must be turned off for 2 weeks for a washout period and remain off during the entirety of the study. Current use of Transcutaneous Electrical Nerve Stimulation (TENS) in pelvic region, back or legs Previous PTNS treatment Participation in any clinical investigation involving or impacting gynecologic, urinary, or renal function within past 4 weeks Note: For the sake of preserving scientific integrity, one or more of the eligibility criteria have been left off the list posted while the trial is ongoing. A full list of eligibility criteria will be posted upon completion of the trial.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Randomized, single-blind, sham controlled.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active PTNS<br>Once a week induction consisting of active PTNS treatments for 30 minutes for 12 consecutive weeks. | Device: PTNS Treatment<br>* Patients will be placed in a comfortable position, sitting or supine. The treatment leg will be propped up comfortably on a footrest but draped and out of view from the patient. A 34-gauge needle electrode will be inserted at a 60-degree angle 5 cm cephalad to the medial malleolus and slightly posterior to the tibia. A PTNS surface electrode will be placed on the ipsilateral calcaneus as well as 2 inactive sham surface electrodes, 1 under the little toe and 1 on the top of the foot. When the PTNS lead set is connected to the Urgent PC stimulator, a current level of 0.5 to 9 mA at 20 Hz is selected based on each patient's foot and plantar motor and sensory responses. Treatment lasts 30 minutes and given once weekly for 12 consecutive weeks.<br>* Other names: Urgent PC Neuromodulation System;|
| Placebo Comparator: Sham PTNS<br>Once a week induction consisting of Sham PTNS treatments for 30 minutes for 12 consecutive weeks. | Device: Sham PTNS Treatment<br>* Patients will be positioned similarly as PTNS patients. A Streitberger needle will be used at the tibial nerve insertion site as described above to simulate needle placement. Three electrodes will be placed on the patient's foot, two active TENS electrodes and one inactive TENS electrode. The TENS grounding pad will be a gel electrode pad from a TENS unit device that is placed on the bottom of the foot just below the smallest toe. Another gel electrode will be placed on the top of the foot just above the small toe for conduction. These two electrodes will be connected to the TENS unit lead wires for sham stimulation. A third, inactive, gel electrode, will be placed near the medial aspect of the calcaneus to mimic the PTNS treatment. The TENS electrode will be connected by lead wires to the TENS unit set at 20 HZ. The TENS unit will be turned on and stimulation slowly increased to the patient's first sensory level and then turned off.<br>* Other names: Biostim TENS Unit;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The overall patient reported change of OAB symptoms in MS patients as reported on the Patient Global Impression of Improvement (PGI-I) questionnaire | The PGI-I is a self-reported measure of symptom change after treatment completion. This is a validated 1-question tool. Subjects score their urinary condition now compared to how it was before starting treatment. The score ranges from 1-7. 1= very much better, 2 = much better, 3 = a little better, 4=no change, 5= a little worse, 6= much worse, 7 = very much worse | One week after completing all 12 treatments, Visit 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urinary symptoms in response to the treatment using a 3-day voiding diary | Study participants will complete a 3-day voiding diary to record number of voids, and the number of urgency and urinary incontinence episodes over a 3-day period. Investigators will analyze the change in urinary symptoms from before to after treatment. | At baseline and one week after completing all 12 treatments, Visit 13 | 
| Change in overactive bladder symptoms in response to the treatment using the Overactive Bladder Quality of Life short form questionnaire. | Patients will complete the Overactive Bladder quality of life questionnaire to help determine the impact of PTNS treatment on patients quality of life. Patients will score severity of symptoms and the impact of the symptom on patient quality of life on a scale from 1-6, with 1 = not at all, 2 = A little bit, 3 = somewhat, 4 = quite a bit, 5 = a great deal, and 6 = a very great deal. | At baseline and one week after completing all 12 treatments, Visit 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, MS, Overactive bladder, OAB