Cycling Versus Continuous Mode in Neuromodulator Programming
Cycling Versus Continuous Mode in Neuromodulator Programming
The investigators objective is to compare patient outcomes as changes in validated symptom
 measures of overactive bladder, the Overactive Bladder Questionnaire Short Form (OABq-SF)
 symptom scale, between women who are set on cycling versus continuous programs for their
 neuromodulator. Specifically, the investigators propose to perform a randomized double blind
 crossover study in women who are successfully treated with neuromodulation to either
 continuous or cycling mode on the modulator and compare differences between groups on the
 validated OABq-SF symptom questionnaire. In addition, the investigators will compare
 differences in urinary frequency and pad counts between women randomized to cycling versus
 continuous stimulation as measured by a 3 day voiding diary. This investigation will provide
 evidence-based guidelines for neuromodulator programming.
Background and Significance:

 The purpose of this research proposal is to evaluate the effect of cycling versus continuous
 neuromodulator programming on overactive bladder syndrome. s.In 1997, the Federal Drug
 Administration (FDA) approved the sacral nerve stimulator as a treatment for refractory urge
 incontinence. Sacral Neuromodulation works via stimulation of the sacral nerve roots 2-4,
 (S-2, S-3 and S-4), although the exact mechanism of action is unknown. While implanted
 electronic stimulators have been used increasingly in the last twenty years, little
 investigation has documented the actual programming of the stimulator. Prospective trials
 examining the ideal programming parameters for a specific condition are needed to better
 identify optimal use of sacral nerve modulation therapy.

 In brief, women with overactive bladder who are refractory to treatment are eligible for a
 trial placement of a neuromodulator. The modulators are placed in two stages; in stage one, a
 temporary lead is placed in the 3rd sacral foramen. Each neuromodulator has 4 electrodes that
 are placed via a single lead into the 3rd sacral foramen. The patient will generally return
 to clinic one week following stage 1 for a post-op evaluation. If the patient reports a 50%
 improvement in frequency as measured on a 3-day voiding diary, the modulator is permanently
 implanted. This is stage 2. After placement, the modulator is programmed in the recovery
 room. Patients are trialed on four set programs for their stimulator. Each program differs in
 electrode combination, pulse width, amplitude and rate as well as direction of current. Each
 of the four programs is tested with the patient to determine which is felt by the patient in
 the perineum and is comfortable. Finally, patients can either have their modulator set on a
 cycling or continuous mode. Currently, decisions regarding programming are made by whoever is
 assessing the patient and are not data driven.

 Typically, cycling means the neuromodulator stimulation is on for 16 seconds & off for 8
 seconds. Continuous means the patient receives constant stimulation. A single retrospective
 study described program parameters for programming of the modulator for treatment of Over
 Active Bladder (OAB). It described 67 patients who had good response to neuromodulation, and
 determined the mean pulse width was 204 microseconds, the pulse width ranged between 120-270
 microseconds; the average rate was 9 with a range of 2-20 pulses/second. The majority of
 women were on cycling mode. Program cycling is purported to decrease the incidence of
 patients reporting that their modulator is no longer working and thought to extend battery
 life. No other study has investigated whether or not cycling of the stimulator improves
 patient outcomes.

 Our objective is to compare patient outcomes using in validated symptom measures of OAB
 between women who are set on cycling versus continuous programs. Investigators propose to
 perform a randomized crossover study in women who are successfully treated with
 neuromodulation to either continuous or cycling mode and compare differences between groups
 on the OAB-q SF symptom questionnaire. The investigators will also compare differences in
 urinary frequency and pad counts between women randomized to cycling versus continuous
 stimulation using voiding diaries.

 Specific Aims and Objectives:

 Aim #1: To compare OAB improvement as measured by the Overactive Bladder Questionnaire Short
 Form Symptom questionnaire (OAB-q SF symptom questionnaire) between women with continuous
 versus cycling stimulation of their neuromodulator.

 Hypothesis #1: Investigators hypothesize that women on cycling programs will report higher
 OAB-q SF symptom scores than women on continuous programs.

 Aim #2: To compare urinary frequency as recorded on 3 day voiding diaries between women
 placed on continuous versus cycling stimulation of their neuromodulator.

 Hypothesis #2: Investigators hypothesize that women on cycling programs report less urinary
 frequency as measured on 3 day voiding diaries than women on continuous programming.

 Aim #3: To compare pad usage between women on cycling programs versus those on continuous
 programs.

 Hypothesis #3: Investigators hypothesize that women on cycling programs will report less pad
 use than women on cycling programs.

 Methods:The investigators will conduct a double-blinded crossover randomized controlled
 clinical trial. Up to 50 women will need to be recruited in order to randomize twenty-three
 women who are successful with the Stage 1 implant of their neuromodulator. After written
 consent, clinical data will be collected and questionnaires administered. After successful
 Stage 1 placement women will complete a 3-day voiding diary. The recording of symptoms and
 completion of a voiding diary are standard of care for women undergoing neuromodulation
 treatment. These data will be collected and recorded.

 Randomization will occur after successful Stage 2 implantation. Study personnel not otherwise
 involved in patient care will assign it. Randomization assignment will be by random number
 table in permutated blocks of four, to ensure that equal numbers of women will be assigned to
 each group. Assignments will be kept in sealed opaque envelopes and will be opened in
 sequential order once women have undergone successful Stage 2 implantation. Study personnel
 programming the modulator after implantation will either program the modulator to continuous
 or cycling programs. Patients will be blinded to randomization assignment.

 Prior to their 3 month visit, study subjects will complete another voiding diary. At the
 visit, women will complete the OAB-q SF symptom questionnaire as well as the Patient Global
 Impression of Improvement (PGI-I). At this visit, women who were assigned to continuous
 stimulation will be switched to cycling stimulation and women who were assigned to cycling
 stimulation will be switched to continuous stimulation. Women again will report for clinical
 follow-up at six months. Women will be asked to complete their voiding diary. At this clinic
 visit women will once again complete the OAB-q SF symptoms questionnaire and PGI-I

 Investigators obtain a written consent from qualifying patient. Patients will then be
 randomized to Cycling or Continuous mode at Stage II implantation.

 Statistics:

 Analysis: Descriptive statistics will be used to describe patient characteristics. The
 analysis of the change in OAB-q SF scores in this 2 group, 2 period (2x2) crossover design
 will be a repeated measures (RM) Analyses of Variance (ANOVA) with both the treatment group
 (cycling versus continuous) and period (first treatment versus second treatment) as repeated
 factors. The possibility of a cross over effect will be accounted for in the analysis by an
 order effect covariate (equal to 1 if cycling is first and 0 if not.) Analysis of urinary
 incontinence episodes and pad counts as recorded on 3 day voiding diaries will be analyzed by
 repeated measures Poisson regression. (Using SAS's PROC GEN MOD with a Poisson distribution)
 Significance is set at p = 0.05.

 Power analysis: In our cross over randomized controlled trial the investigators assume that a
 clinically important difference between changes in OAB-q SF scores between women on
 continuous versus cycling stimulation, with a standard deviation of the paired differences of
 15 points between groups with an alpha error of 0.05 and power of 80%, 20 women are needed to
 be randomized into equal groups.

 (Hintze, J (2011) PASS11. NCSS, LLC< Kaysville Utah, US. www.ncss.com)(9), Assuming that 15%
 of women will be lost to follow-up the investigators will need to randomize 23 women to the
 study.

 2. Expected outcome: This randomized control trial will demonstrate that women on the cycling
 program mode will report higher OAB-q SF Symptom scores, and will report less urinary
 frequency and less pad usage as measured on 3-day voiding diaries.
Inclusion Criteria:

 -  Women at least 21 years old or older eligible for implantation of a neuromodulator

 -  Women with successful Stage #1 implantation for treatment of refractory OAB

 -  Subjects may be enrolled in other studies as long as there are no changes to the
 neuromodulation device. Women may continue other OAB therapies that they are on, but
 as asked to not start new therapies.

 -  Not currently pregnant and with no plans to become pregnant during the course of the
 trial.

 -  Willing as well as mentally and physically capable of completing all study related
 procedures and materials

 Exclusion Criteria:

 -  Males (we do not care for males in our urogynecology clinic)

 -  Incarcerated women

 -  Non-English speakers

 -  Pregnant women

 -  Scheduled or planned MRIs or diathermy