Multiple Sclerosis, Overactive Bladder
Conditions
Keywords
Multiple Sclerosis, MS, Overactive bladder, OAB
Brief summary
This is a pilot, single blind, randomized, sham-controlled trial to assess the benefit of Percutaneous Tibial Nerve Stimulation (PTNS) in treating bladder overactivity (OAB) symptoms in multiple sclerosis (MS) patients. The data generated by this study would provide support for a future multi-institutional, randomized prospective trial.
Detailed description
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 OAB and urinary incontinence (UI) being the predominant bladder dysfunctions. OAB is characterized by sudden feeling of urgency, frequent urination, and urge incontinence. 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.
Interventions
DEVICEPTNS Treatment
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.
DEVICESham PTNS Treatment
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.
Sponsors
Corewell Health East
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participant will be blinded to treatment group. Only the clinician providing the treatment will be aware of the treatment group assignment.
Intervention model description
Randomized, single-blind, sham controlled.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women with diagnosis for Multiple Sclerosis (Clinically isolated syndrome (CIS), relapsing remitting (RRMS), secondary progressive (SPMS), and/or primary progressive (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, intrauterine device (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 * Botox (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Overall Patient Reported Change of Bladder Overactivity (OAB) Symptoms in MS Patients as Reported on the Patient Global Impression of Improvement (PGI-I) Questionnaire | One week after completing all 12 treatments | 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. A higher score indicates a worse outcome. Only one participant completed the primary outcome, thus that subject score will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Voids in Response to the Treatment Using a 3-day Voiding Diary | At baseline and one week after completing all 12 treatments, Visit 13 | Study participants will complete a 3-day voiding diary to record number of voids. Investigators will analyze the change in urinary voids from before to after treatment. A positive number indicates more voids, and a negative number indicates fewer voids. |
| Change in Urinary Incontinence Episodes in Response to the Treatment Using a 3-day Voiding Diary | At baseline and one week after completing all 12 treatments, Visit 13 | Study participants will complete a 3-day voiding diary to record number of urinary incontinence episodes over a 3-day period. Investigators will analyze the change in urinary incontinence episodes from before to after treatment. A positive number indicates more episodes, and a negative number indicates fewer episodes. |
| Change in Urinary Urgency Episodes in Response to the Treatment Using a 3-day Voiding Diary | At baseline and one week after completing all 12 treatments, Visit 13 | Study participants will complete a 3-day voiding diary to record the number of urgency episodes over a 3-day period. Investigators will analyze the change in urinary urgency episodes from before to after treatment. A positive number indicates more episodes, and a negative number indicates fewer episodes. |
| Change in Overactive Bladder Symptoms in Response to the Treatment Using the Overactive Bladder Quality of Life Short Form Questionnaire. | At baseline and one week after completing all 12 treatments, Visit 13 | The Overactive Bladder quality of life questionnaire measures the impact of PTNS treatment on patient quality of life. Patients score symptom severity and impact on quality of life on a scale 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. Symptom severity raw score is calculated from questions 1-6; the lowest possible raw score is 6, the highest score is 36. The health-related quality of life (HRQL) raw score is calculated similarly from questions 1-13; the lowest possible score is 13 and highest score is 78. The formula (actual raw score - lowest possible raw score)/highest possible raw score times 100 is applied to each raw score, which are added to give a final score in the range 0 to 166.6, with low scores indicating fewer symptoms and impact, and high scores indicating more symptoms and impact. Change from baseline is reported, with a positive number indicating worsening and a negative number indicating improvement. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from December 2022 through December 2023.
Participants by arm
| Arm | Count |
|---|---|
| Active PTNS Once a week induction consisting of active PTNS treatments for 30 minutes for 12 consecutive weeks.
PTNS Treatment: 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. | 2 |
| Sham PTNS Once a week induction consisting of Sham PTNS treatments for 30 minutes for 12 consecutive weeks.
Sham PTNS Treatment: 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. | 0 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sham PTNS | Total | Active PTNS |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Continuous | — | 47 years STANDARD_DEVIATION 12 | 47 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment United States | — | 2 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 0 |
| other Total, other adverse events | 0 / 2 | 0 / 0 |
| serious Total, serious adverse events | 0 / 2 | 0 / 0 |
Outcome results
Primary
The Overall Patient Reported Change of Bladder Overactivity (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. A higher score indicates a worse outcome. Only one participant completed the primary outcome, thus that subject score will be reported.
Time frame: One week after completing all 12 treatments
Population: Of the 2 patients enrolled, only 1 patient completed the study and the primary outcome measure. The other subject withdrew prior to the primary outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active PTNS | The Overall Patient Reported Change of Bladder Overactivity (OAB) Symptoms in MS Patients as Reported on the Patient Global Impression of Improvement (PGI-I) Questionnaire | 4 score |
Secondary
Change in Overactive Bladder Symptoms in Response to the Treatment Using the Overactive Bladder Quality of Life Short Form Questionnaire.
The Overactive Bladder quality of life questionnaire measures the impact of PTNS treatment on patient quality of life. Patients score symptom severity and impact on quality of life on a scale 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. Symptom severity raw score is calculated from questions 1-6; the lowest possible raw score is 6, the highest score is 36. The health-related quality of life (HRQL) raw score is calculated similarly from questions 1-13; the lowest possible score is 13 and highest score is 78. The formula (actual raw score - lowest possible raw score)/highest possible raw score times 100 is applied to each raw score, which are added to give a final score in the range 0 to 166.6, with low scores indicating fewer symptoms and impact, and high scores indicating more symptoms and impact. Change from baseline is reported, with a positive number indicating worsening and a negative number indicating improvement.
Time frame: At baseline and one week after completing all 12 treatments, Visit 13
Population: Of the 2 patients enrolled, only 1 patient completed the study and the secondary outcome measure. The other subject withdrew prior to the secondary outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active PTNS | Change in Overactive Bladder Symptoms in Response to the Treatment Using the Overactive Bladder Quality of Life Short Form Questionnaire. | -47.69 score on a scale | Standard Deviation 0 |
Secondary
Change in Urinary Incontinence Episodes in Response to the Treatment Using a 3-day Voiding Diary
Study participants will complete a 3-day voiding diary to record number of urinary incontinence episodes over a 3-day period. Investigators will analyze the change in urinary incontinence episodes from before to after treatment. A positive number indicates more episodes, and a negative number indicates fewer episodes.
Time frame: At baseline and one week after completing all 12 treatments, Visit 13
Population: Of the 2 patients enrolled, only 1 patient completed the study and the secondary outcome measure. The other subject withdrew prior to the secondary outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active PTNS | Change in Urinary Incontinence Episodes in Response to the Treatment Using a 3-day Voiding Diary | -3 number of urgency incontinence episodes | Standard Deviation 0 |
Secondary
Change in Urinary Urgency Episodes in Response to the Treatment Using a 3-day Voiding Diary
Study participants will complete a 3-day voiding diary to record the number of urgency episodes over a 3-day period. Investigators will analyze the change in urinary urgency episodes from before to after treatment. A positive number indicates more episodes, and a negative number indicates fewer episodes.
Time frame: At baseline and one week after completing all 12 treatments, Visit 13
Population: Of the 2 patients enrolled, only 1 patient completed the study and the secondary outcome measure. The other subject withdrew prior to the secondary outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active PTNS | Change in Urinary Urgency Episodes in Response to the Treatment Using a 3-day Voiding Diary | 1 number of urgency episodes | Standard Deviation 0 |
Secondary
Change in Urinary Voids 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. Investigators will analyze the change in urinary voids from before to after treatment. A positive number indicates more voids, and a negative number indicates fewer voids.
Time frame: At baseline and one week after completing all 12 treatments, Visit 13
Population: Of the 2 patients enrolled, only 1 patient completed the study and the secondary outcome measure. The other subject withdrew prior to the secondary outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active PTNS | Change in Urinary Voids in Response to the Treatment Using a 3-day Voiding Diary | 1 number of voids | Standard Deviation 0 |