Protocol for Brain-Centered Therapy Versus Medication for Urgency Urinary Incontinence An RCT: Hypnotherapy Or Pharmacotherapy View Homepage


Ontology type: schema:MedicalStudy     


Clinical Trial Info

YEARS

2013-2017

ABSTRACT

This study is randomized controlled trial in which urgency incontinent women (approximately 150-160) will be randomized to hypnotherapy or pharmacotherapy and evaluated at months 2, 6 &12; a subset of women will have pre-treatment brain activation and connectivity compared to controls using functional magnetic imaging (fMRI) with 2 month post-treatment brain activation and connectivity compared to pre-treatment in the UUI subset using fMRI. Hypotheses: Among patients with urgency urinary incontinence (UUI), hypnotherapy decreases abnormal perception of bladder distension outside the hypnotic state and is at least as effective as pharmacotherapy in diminishing symptoms of urgency and severity of UUI. On fMRI in UUI, hypnotherapy will decrease hyper-activation of brain areas in response to bladder distension and/or modulate functional connectivity within the brain. Normalization of hyper-activation and connectivity will be greater in hypnotherapy compared to pharmacotherapy. Additionally, women who have greater improvement in UUI will have greater normalization of hyper-activation and connectivity on fMRI. UUI participants will exhibit increased activation within portions of the brain and abnormal functional connectivity relative to controls. Detailed Description Study Objectives Primary: To compare change in Urgency Urinary Incontinence (UUI) episodes at 2 month follow-up on voiding diaries between hypnotherapy and pharmacotherapy groups (to determine whether hypnotherapy is at least as effective and durable in treating UUI as pharmacotherapy) and change in brain activation and connectivity on functional Magnetic Resonance Imaging (fMRI) in the subset of UUI participants who have undergone fMRI Secondary: - To determine whether hypnotherapy is at least as effective and durable, in treating UUI as pharmacotherapy comparing change in UUI episodes on voiding diary at 6 and 12 month follow-up - To determine whether hypnotherapy is at least as effective and durable, in treating UUI as pharmacotherapy comparing change in questionnaire results and urinary frequency and pad counts on voiding diaries - To determine baseline symptoms occurrence of concomitant syndromes (e.g. irritable bowel syndrome, constipation, anal incontinence, painful bladder syndrome) in this UUI population based on medical history and questionnaires. And to explore whether these symptoms change following treatment, assuming sufficient numbers of women at baseline. - To confirm differences in brain activation and connectivity on fMRI in UUI compared to controls at baseline Overview: Women with UUI meeting criteria will give informed consent and be enrolled following administration of the OAB Awareness tool. Participants will keep voiding diaries then be randomized to either pharmacotherapy and conventional behavioral therapy or hypnotherapy and conventional behavioral therapy. Approximately 150-160 women will be randomized. Randomization will occur using a computer-generated randomization scheme in varying permuted block sizes. Investigators analyzing fMRI results, investigators analyzing RCT results and study personnel performing data entry will be blinded to participants' treatment. Blinding participants to treatment is not feasible. UUI participants will be followed in the study approximately 1 year. Measurements will be performed before treatment, following completion of treatment visits (approximately 8 weeks), and at 6 and 12 months. RCT primary analysis will be intention to treat. Secondary analyses will be per protocol. A subset of approximately UUI 60-70 participants (from both treatment groups) will undergo functional MRI (fMRI) pre and post-treatment. Approximately 20-30 controls will undergo fMRI. Outcomes will be differences in baseline brain activation and resting connectivity in UUI compared to controls, and post-treatment differences in brain activation and connectivity in UUI. Study Visits: UUI participant screening: Study information given. Screening questionnaire given. Visit 1 Enrollment: Formal screening for eligibility, voiding diary reviewed, if eligible, written consent obtained followed by 1) study questionnaires, demographic and past medical history administration 2) Pelvic Organ Prolapse Quantitation (POP-Q) exam 3) cystometry, hypnotic susceptibility testing scheduled 4) those willing/able to undergo fMRI are screened and scheduled 6) behavioral interventions discussed, hand-out given. Visit 2: Cystometry performed. FMRI subjects also undergo brief fMRI task simulations. Subjects undergo hypnotic susceptibility testing (if not feasible, testing performed at separate visit before randomization). Visit 3: fMRI UUI participants: Baseline fMRI performed. Randomization: Participants randomized to treatment and contacted, treatments arranged. Visits 3-10 for Hypnotherapy (for non-fMRI group), Visits 4-11 (for fMRI group) for Hypnotherapy—Women assigned to Hypnotherapy undergo weekly treatments over 8 weeks. Visits 3-10 for Pharmacotherapy (for non-fMRI group), Visits 4-11 (for fMRI group) for Pharmacotherapy--Medication Counseling Sessions: Women assigned to pharmacotherapy have weekly counseling sessions over 8 weeks. Visit 12 (for FMRI group)—follow-up fMRI performed. Post Therapy visit--Visit 11 (for non-fMRI group), Visit 13 (for fMRI group): Following hypnotherapy or medication counseling completion participants return voiding diaries and administered study questionnaires. 6 & 12 month follow-up: conducted via phone, in person, or mail. Pharmacotherapy subjects receive medications for 1 year and Hypnotherapy subjects encouraged to continue self-hypnosis for 1 year. Controls in FMRI study: screened with OAB Awareness Tool, voiding diary, and give informed consent. Undergo POP-Q exam, answer demographic questions, undergo cystometry and simulation of fMRI tasks. FMRI performed at separate visit. Interventions: Hypnotherapy: Administered over approximately 8 weeks by certified, trained clinical hypnotherapists. Participants informed sessions are audio-recorded and reviewed ensuring hypnotherapy standardly administered, receive digital recordings specially prepared for them for self-hypnosis. Pharmacotherapy: Counseling sessions administered over approximately 8 weeks by trained medication counselor who reviews medications and side effects. Participant informed sessions are audio-recorded and reviewed ensuring counseling is standardly administered. Majority of 8 weekly visits may occur via phone if in-person visits are burdensome. One of two long acting anti-cholinergic medications and dosages offered (Long acting Tolterodine or Extended Release Oxybutynin or equivalent generic substitutes). Participants continue to receive medications for one year. FMRI Description: FMRI Data Acquisition: High resolution T1 anatomic images collected at beginning of each session. Echo-planar images collected using a single-shot, gradient-echo. FMRI Task: Presentation software programmed to control stimulus presentation, synchronize stimulus events and collect data. Subjects instructed to maintain visual fixation on centrally presented cross and eye-tracking device records saccades while scanned while undergoing bladder filling and emptying. Image Processing: fMRI data obtained during tasks include slice, temporal auto-correlations and motion corrections. Voxel-wise multiple regression analysis used to estimate beta weights corresponding to functional activation resulting from each of the conditions. Multiple regression contains individually tailored demeaned regressors corresponding to subject's desire to void (urge regressor), resembling a step function; each button press signals increasing/decreasing levels of desire to void which are convolved with a gamma variate function derived from parameters of the hemodynamic response. A regressor corresponding to bladder emptying/filling created by convolving the experimental time-course with a gamma variate function, and connectivity analyses are performed. Functional connectivity is measured between specific points and the remainder of the brain. Averaged individual residualized time-courses from these spheres are the primary regressor in whole-brain BOLD connectivity analyses. Pearson's correlation coefficients will be converted to z-scores using Fisher's method and blurred using a 10 mm Gaussian kernel contrasted across the groups using independent sample T-tests. Statistical Analysis: For RCT- Investigators performed sample size calculations for change in UUI episodes and change in OABq-SF scores based on investigators' pilot data & the literature.6,7 The study will use a non-inferiority design for the primary outcome (UUI episode changes in hypnotherapy versus pharmacotherapy). A one-sided non-inferiority test with alpha = 0.025 and a non-inferiority margin of 5% will be used. If μ_h is the population mean percent reduction in UUI episodes for hypnotherapy, and μ_m is the population mean percent reduction in UUI episodes for medication, investigators will test H_0:μ_h-μ_m≤-5 against the one-sided alternative H_0:μ_h-μ_m>-5 using significance level 0.025. If the null hypothesis is rejected, investigators may conclude hypnotherapy is not inferior to medication, on average, by more than 5%, and in fact may be superior to medication therapy, in percent reduction in incontinence episodes. The test may be performed by computing the lower 97.5% one-sided confidence bound for μ_h-μ_m. If the lower confidence bound exceeds -5% investigators will conclude non-inferiority of hypnotherapy. Superiority will be concluded if the lower bound exceeds zero. Assuming drop-out, withdrawal, missing data rates as high as 33%, 52 subjects will be available for analysis in both groups. If μ_h-μ_m≥9%, sample size would provide power ≥ 80% for non-inferiority testing. Improvement between groups will be compared at baseline and 2, 6, 12 month follow-up. Parameters will be compared using a generalized linear mixed model analysis. If baseline differences between groups are found, appropriate variables will be added to the analysis as covariates. Primary analyses will be performed using intention to treat. Per protocol analysis will additionally be performed. Similar analyses will be performed comparing group differences in change in questionnaire scores. For FMRI analysis: Change in anterior cingulate cortex and insula activation between groups at 2 month follow-up. A 2x2 (GroupxTime) mixed model ANCOVA to correct for potential differences in group characteristics will be performed. Analysis will focus on the anterior cingulate cortex and insula based on preliminary data suggesting the effect size for activation changes will be highest in these regions. Study size will be able to detect differences between pre and post-treatment signal within groups with an approximate effect size of 0.5 and a power of 0.8. Minimal effect size would be approximately equivalent to a 60% decrease in the anterior cingulate cortex and insula. Investigators predict a main effect of time, suggesting both treatments reduce activity within these regions. Investigators also predict a significant GroupxTime interaction, indicating change in activity will be greater for hypnotherapy. Minimum detectable effect size for the GroupXTime interaction is 0.7; power=0.8, alpha=0.05. Simple effects tests will be conducted to ensure randomization to treatment arm was successful. Similar analyses will be conducted to evaluate treatment effects on functional connectivity. Study size will be able to detect within-group differences between pre and post-treatment signal; minimal effect size of approximately 0.5, power=0.8, lower than the effect size of >3 in the pilot. Minimum effect size would be reached with a 15% decrement in anterior cingulate cortex to insula connectivity. For evoked activity investigators predict a main effect of time and a significant Group x Time interaction (change in functional connectivity will be greater for hypnotherapy relative to pharmacotherapy). Minimum detectable effect size for Group X Time interaction=0.7; power=0.8, alpha=0.05.This minimum effect size will be reached when between group differences in anterior cingulate cortex to insula connectivity are ≥ 30%. Baseline analysis: Controls vs. UUI at baseline. Regions of interest containing the insula and anterior cingulate cortex will be analyzed using two way ANCOVA with group as the between subject's factor. Pre-treatment β weights for bladder filling and urgency regressor effect on anterior cingulate cortex and insula signal among controls will be compared to UUI. Study size allows detection of between group differences with effect size >0.8, power=0.8, smaller than that in the pilot study.43 The effect size in the pilot (Cohen's d= 0.8-1.5) suggests the study will be adequately powered to reject the null hypothesis. Group-wise whole brain contrast will be performed using the same statistical model. False positives will be corrected at significance of p <.005,with a minimum cluster size of 32 voxels (p < 0.05) derived from 10,000 Monte Carlo simulations.80 Functional connectivity will be performed similarly to that used to analyze task brain activation. More... »

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https://clinicaltrials.gov/show/NCT01829425

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    "description": "This study is randomized controlled trial in which urgency incontinent women (approximately 150-160) will be randomized to hypnotherapy or pharmacotherapy and evaluated at months 2, 6 &12; a subset of women will have pre-treatment brain activation and connectivity compared to controls using functional magnetic imaging (fMRI) with 2 month post-treatment brain activation and connectivity compared to pre-treatment in the UUI subset using fMRI. Hypotheses: Among patients with urgency urinary incontinence (UUI), hypnotherapy decreases abnormal perception of bladder distension outside the hypnotic state and is at least as effective as pharmacotherapy in diminishing symptoms of urgency and severity of UUI. On fMRI in UUI, hypnotherapy will decrease hyper-activation of brain areas in response to bladder distension and/or modulate functional connectivity within the brain. Normalization of hyper-activation and connectivity will be greater in hypnotherapy compared to pharmacotherapy. Additionally, women who have greater improvement in UUI will have greater normalization of hyper-activation and connectivity on fMRI. UUI participants will exhibit increased activation within portions of the brain and abnormal functional connectivity relative to controls.\n\nDetailed Description\nStudy Objectives Primary: To compare change in Urgency Urinary Incontinence (UUI) episodes at 2 month follow-up on voiding diaries between hypnotherapy and pharmacotherapy groups (to determine whether hypnotherapy is at least as effective and durable in treating UUI as pharmacotherapy) and change in brain activation and connectivity on functional Magnetic Resonance Imaging (fMRI) in the subset of UUI participants who have undergone fMRI Secondary: - To determine whether hypnotherapy is at least as effective and durable, in treating UUI as pharmacotherapy comparing change in UUI episodes on voiding diary at 6 and 12 month follow-up - To determine whether hypnotherapy is at least as effective and durable, in treating UUI as pharmacotherapy comparing change in questionnaire results and urinary frequency and pad counts on voiding diaries - To determine baseline symptoms occurrence of concomitant syndromes (e.g. irritable bowel syndrome, constipation, anal incontinence, painful bladder syndrome) in this UUI population based on medical history and questionnaires. And to explore whether these symptoms change following treatment, assuming sufficient numbers of women at baseline. - To confirm differences in brain activation and connectivity on fMRI in UUI compared to controls at baseline Overview: Women with UUI meeting criteria will give informed consent and be enrolled following administration of the OAB Awareness tool. Participants will keep voiding diaries then be randomized to either pharmacotherapy and conventional behavioral therapy or hypnotherapy and conventional behavioral therapy. Approximately 150-160 women will be randomized. Randomization will occur using a computer-generated randomization scheme in varying permuted block sizes. Investigators analyzing fMRI results, investigators analyzing RCT results and study personnel performing data entry will be blinded to participants' treatment. Blinding participants to treatment is not feasible. UUI participants will be followed in the study approximately 1 year. Measurements will be performed before treatment, following completion of treatment visits (approximately 8 weeks), and at 6 and 12 months. RCT primary analysis will be intention to treat. Secondary analyses will be per protocol. A subset of approximately UUI 60-70 participants (from both treatment groups) will undergo functional MRI (fMRI) pre and post-treatment. Approximately 20-30 controls will undergo fMRI. Outcomes will be differences in baseline brain activation and resting connectivity in UUI compared to controls, and post-treatment differences in brain activation and connectivity in UUI. Study Visits: UUI participant screening: Study information given. Screening questionnaire given. Visit 1 Enrollment: Formal screening for eligibility, voiding diary reviewed, if eligible, written consent obtained followed by 1) study questionnaires, demographic and past medical history administration 2) Pelvic Organ Prolapse Quantitation (POP-Q) exam 3) cystometry, hypnotic susceptibility testing scheduled 4) those willing/able to undergo fMRI are screened and scheduled 6) behavioral interventions discussed, hand-out given. Visit 2: Cystometry performed. FMRI subjects also undergo brief fMRI task simulations. Subjects undergo hypnotic susceptibility testing (if not feasible, testing performed at separate visit before randomization). Visit 3: fMRI UUI participants: Baseline fMRI performed. Randomization: Participants randomized to treatment and contacted, treatments arranged. Visits 3-10 for Hypnotherapy (for non-fMRI group), Visits 4-11 (for fMRI group) for Hypnotherapy\u2014Women assigned to Hypnotherapy undergo weekly treatments over 8 weeks. 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Interventions: Hypnotherapy: Administered over approximately 8 weeks by certified, trained clinical hypnotherapists. Participants informed sessions are audio-recorded and reviewed ensuring hypnotherapy standardly administered, receive digital recordings specially prepared for them for self-hypnosis. Pharmacotherapy: Counseling sessions administered over approximately 8 weeks by trained medication counselor who reviews medications and side effects. Participant informed sessions are audio-recorded and reviewed ensuring counseling is standardly administered. Majority of 8 weekly visits may occur via phone if in-person visits are burdensome. One of two long acting anti-cholinergic medications and dosages offered (Long acting Tolterodine or Extended Release Oxybutynin or equivalent generic substitutes). Participants continue to receive medications for one year. FMRI Description: FMRI Data Acquisition: High resolution T1 anatomic images collected at beginning of each session. 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A regressor corresponding to bladder emptying/filling created by convolving the experimental time-course with a gamma variate function, and connectivity analyses are performed. Functional connectivity is measured between specific points and the remainder of the brain. Averaged individual residualized time-courses from these spheres are the primary regressor in whole-brain BOLD connectivity analyses. Pearson's correlation coefficients will be converted to z-scores using Fisher's method and blurred using a 10 mm Gaussian kernel contrasted across the groups using independent sample T-tests. Statistical Analysis: For RCT- Investigators performed sample size calculations for change in UUI episodes and change in OABq-SF scores based on investigators' pilot data & the literature.6,7 The study will use a non-inferiority design for the primary outcome (UUI episode changes in hypnotherapy versus pharmacotherapy). A one-sided non-inferiority test with alpha = 0.025 and a non-inferiority margin of 5% will be used. If \u03bc_h is the population mean percent reduction in UUI episodes for hypnotherapy, and \u03bc_m is the population mean percent reduction in UUI episodes for medication, investigators will test H_0:\u03bc_h-\u03bc_m\u2264-5 against the one-sided alternative H_0:\u03bc_h-\u03bc_m>-5 using significance level 0.025. If the null hypothesis is rejected, investigators may conclude hypnotherapy is not inferior to medication, on average, by more than 5%, and in fact may be superior to medication therapy, in percent reduction in incontinence episodes. The test may be performed by computing the lower 97.5% one-sided confidence bound for \u03bc_h-\u03bc_m. If the lower confidence bound exceeds -5% investigators will conclude non-inferiority of hypnotherapy. Superiority will be concluded if the lower bound exceeds zero. 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Analysis will focus on the anterior cingulate cortex and insula based on preliminary data suggesting the effect size for activation changes will be highest in these regions. Study size will be able to detect differences between pre and post-treatment signal within groups with an approximate effect size of 0.5 and a power of 0.8. Minimal effect size would be approximately equivalent to a 60% decrease in the anterior cingulate cortex and insula. Investigators predict a main effect of time, suggesting both treatments reduce activity within these regions. Investigators also predict a significant GroupxTime interaction, indicating change in activity will be greater for hypnotherapy. Minimum detectable effect size for the GroupXTime interaction is 0.7; power=0.8, alpha=0.05. Simple effects tests will be conducted to ensure randomization to treatment arm was successful. Similar analyses will be conducted to evaluate treatment effects on functional connectivity. Study size will be able to detect within-group differences between pre and post-treatment signal; minimal effect size of approximately 0.5, power=0.8, lower than the effect size of >3 in the pilot. Minimum effect size would be reached with a 15% decrement in anterior cingulate cortex to insula connectivity. For evoked activity investigators predict a main effect of time and a significant Group x Time interaction (change in functional connectivity will be greater for hypnotherapy relative to pharmacotherapy). Minimum detectable effect size for Group X Time interaction=0.7; power=0.8, alpha=0.05.This minimum effect size will be reached when between group differences in anterior cingulate cortex to insula connectivity are \u2265 30%. Baseline analysis: Controls vs. UUI at baseline. Regions of interest containing the insula and anterior cingulate cortex will be analyzed using two way ANCOVA with group as the between subject's factor. 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Subject Predicate Object
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2 schema:description This study is randomized controlled trial in which urgency incontinent women (approximately 150-160) will be randomized to hypnotherapy or pharmacotherapy and evaluated at months 2, 6 &12; a subset of women will have pre-treatment brain activation and connectivity compared to controls using functional magnetic imaging (fMRI) with 2 month post-treatment brain activation and connectivity compared to pre-treatment in the UUI subset using fMRI. Hypotheses: Among patients with urgency urinary incontinence (UUI), hypnotherapy decreases abnormal perception of bladder distension outside the hypnotic state and is at least as effective as pharmacotherapy in diminishing symptoms of urgency and severity of UUI. On fMRI in UUI, hypnotherapy will decrease hyper-activation of brain areas in response to bladder distension and/or modulate functional connectivity within the brain. Normalization of hyper-activation and connectivity will be greater in hypnotherapy compared to pharmacotherapy. Additionally, women who have greater improvement in UUI will have greater normalization of hyper-activation and connectivity on fMRI. UUI participants will exhibit increased activation within portions of the brain and abnormal functional connectivity relative to controls. Detailed Description Study Objectives Primary: To compare change in Urgency Urinary Incontinence (UUI) episodes at 2 month follow-up on voiding diaries between hypnotherapy and pharmacotherapy groups (to determine whether hypnotherapy is at least as effective and durable in treating UUI as pharmacotherapy) and change in brain activation and connectivity on functional Magnetic Resonance Imaging (fMRI) in the subset of UUI participants who have undergone fMRI Secondary: - To determine whether hypnotherapy is at least as effective and durable, in treating UUI as pharmacotherapy comparing change in UUI episodes on voiding diary at 6 and 12 month follow-up - To determine whether hypnotherapy is at least as effective and durable, in treating UUI as pharmacotherapy comparing change in questionnaire results and urinary frequency and pad counts on voiding diaries - To determine baseline symptoms occurrence of concomitant syndromes (e.g. irritable bowel syndrome, constipation, anal incontinence, painful bladder syndrome) in this UUI population based on medical history and questionnaires. And to explore whether these symptoms change following treatment, assuming sufficient numbers of women at baseline. - To confirm differences in brain activation and connectivity on fMRI in UUI compared to controls at baseline Overview: Women with UUI meeting criteria will give informed consent and be enrolled following administration of the OAB Awareness tool. Participants will keep voiding diaries then be randomized to either pharmacotherapy and conventional behavioral therapy or hypnotherapy and conventional behavioral therapy. Approximately 150-160 women will be randomized. Randomization will occur using a computer-generated randomization scheme in varying permuted block sizes. Investigators analyzing fMRI results, investigators analyzing RCT results and study personnel performing data entry will be blinded to participants' treatment. Blinding participants to treatment is not feasible. UUI participants will be followed in the study approximately 1 year. Measurements will be performed before treatment, following completion of treatment visits (approximately 8 weeks), and at 6 and 12 months. RCT primary analysis will be intention to treat. Secondary analyses will be per protocol. A subset of approximately UUI 60-70 participants (from both treatment groups) will undergo functional MRI (fMRI) pre and post-treatment. Approximately 20-30 controls will undergo fMRI. Outcomes will be differences in baseline brain activation and resting connectivity in UUI compared to controls, and post-treatment differences in brain activation and connectivity in UUI. Study Visits: UUI participant screening: Study information given. Screening questionnaire given. Visit 1 Enrollment: Formal screening for eligibility, voiding diary reviewed, if eligible, written consent obtained followed by 1) study questionnaires, demographic and past medical history administration 2) Pelvic Organ Prolapse Quantitation (POP-Q) exam 3) cystometry, hypnotic susceptibility testing scheduled 4) those willing/able to undergo fMRI are screened and scheduled 6) behavioral interventions discussed, hand-out given. Visit 2: Cystometry performed. FMRI subjects also undergo brief fMRI task simulations. Subjects undergo hypnotic susceptibility testing (if not feasible, testing performed at separate visit before randomization). Visit 3: fMRI UUI participants: Baseline fMRI performed. Randomization: Participants randomized to treatment and contacted, treatments arranged. Visits 3-10 for Hypnotherapy (for non-fMRI group), Visits 4-11 (for fMRI group) for Hypnotherapy—Women assigned to Hypnotherapy undergo weekly treatments over 8 weeks. Visits 3-10 for Pharmacotherapy (for non-fMRI group), Visits 4-11 (for fMRI group) for Pharmacotherapy--Medication Counseling Sessions: Women assigned to pharmacotherapy have weekly counseling sessions over 8 weeks. Visit 12 (for FMRI group)—follow-up fMRI performed. Post Therapy visit--Visit 11 (for non-fMRI group), Visit 13 (for fMRI group): Following hypnotherapy or medication counseling completion participants return voiding diaries and administered study questionnaires. 6 & 12 month follow-up: conducted via phone, in person, or mail. Pharmacotherapy subjects receive medications for 1 year and Hypnotherapy subjects encouraged to continue self-hypnosis for 1 year. Controls in FMRI study: screened with OAB Awareness Tool, voiding diary, and give informed consent. Undergo POP-Q exam, answer demographic questions, undergo cystometry and simulation of fMRI tasks. FMRI performed at separate visit. Interventions: Hypnotherapy: Administered over approximately 8 weeks by certified, trained clinical hypnotherapists. Participants informed sessions are audio-recorded and reviewed ensuring hypnotherapy standardly administered, receive digital recordings specially prepared for them for self-hypnosis. Pharmacotherapy: Counseling sessions administered over approximately 8 weeks by trained medication counselor who reviews medications and side effects. Participant informed sessions are audio-recorded and reviewed ensuring counseling is standardly administered. Majority of 8 weekly visits may occur via phone if in-person visits are burdensome. One of two long acting anti-cholinergic medications and dosages offered (Long acting Tolterodine or Extended Release Oxybutynin or equivalent generic substitutes). Participants continue to receive medications for one year. FMRI Description: FMRI Data Acquisition: High resolution T1 anatomic images collected at beginning of each session. Echo-planar images collected using a single-shot, gradient-echo. FMRI Task: Presentation software programmed to control stimulus presentation, synchronize stimulus events and collect data. Subjects instructed to maintain visual fixation on centrally presented cross and eye-tracking device records saccades while scanned while undergoing bladder filling and emptying. Image Processing: fMRI data obtained during tasks include slice, temporal auto-correlations and motion corrections. Voxel-wise multiple regression analysis used to estimate beta weights corresponding to functional activation resulting from each of the conditions. Multiple regression contains individually tailored demeaned regressors corresponding to subject's desire to void (urge regressor), resembling a step function; each button press signals increasing/decreasing levels of desire to void which are convolved with a gamma variate function derived from parameters of the hemodynamic response. A regressor corresponding to bladder emptying/filling created by convolving the experimental time-course with a gamma variate function, and connectivity analyses are performed. Functional connectivity is measured between specific points and the remainder of the brain. Averaged individual residualized time-courses from these spheres are the primary regressor in whole-brain BOLD connectivity analyses. Pearson's correlation coefficients will be converted to z-scores using Fisher's method and blurred using a 10 mm Gaussian kernel contrasted across the groups using independent sample T-tests. Statistical Analysis: For RCT- Investigators performed sample size calculations for change in UUI episodes and change in OABq-SF scores based on investigators' pilot data & the literature.6,7 The study will use a non-inferiority design for the primary outcome (UUI episode changes in hypnotherapy versus pharmacotherapy). A one-sided non-inferiority test with alpha = 0.025 and a non-inferiority margin of 5% will be used. If μ_h is the population mean percent reduction in UUI episodes for hypnotherapy, and μ_m is the population mean percent reduction in UUI episodes for medication, investigators will test H_0:μ_h-μ_m≤-5 against the one-sided alternative H_0:μ_h-μ_m>-5 using significance level 0.025. If the null hypothesis is rejected, investigators may conclude hypnotherapy is not inferior to medication, on average, by more than 5%, and in fact may be superior to medication therapy, in percent reduction in incontinence episodes. The test may be performed by computing the lower 97.5% one-sided confidence bound for μ_h-μ_m. If the lower confidence bound exceeds -5% investigators will conclude non-inferiority of hypnotherapy. Superiority will be concluded if the lower bound exceeds zero. Assuming drop-out, withdrawal, missing data rates as high as 33%, 52 subjects will be available for analysis in both groups. If μ_h-μ_m≥9%, sample size would provide power ≥ 80% for non-inferiority testing. Improvement between groups will be compared at baseline and 2, 6, 12 month follow-up. Parameters will be compared using a generalized linear mixed model analysis. If baseline differences between groups are found, appropriate variables will be added to the analysis as covariates. Primary analyses will be performed using intention to treat. Per protocol analysis will additionally be performed. Similar analyses will be performed comparing group differences in change in questionnaire scores. For FMRI analysis: Change in anterior cingulate cortex and insula activation between groups at 2 month follow-up. A 2x2 (GroupxTime) mixed model ANCOVA to correct for potential differences in group characteristics will be performed. Analysis will focus on the anterior cingulate cortex and insula based on preliminary data suggesting the effect size for activation changes will be highest in these regions. Study size will be able to detect differences between pre and post-treatment signal within groups with an approximate effect size of 0.5 and a power of 0.8. Minimal effect size would be approximately equivalent to a 60% decrease in the anterior cingulate cortex and insula. Investigators predict a main effect of time, suggesting both treatments reduce activity within these regions. Investigators also predict a significant GroupxTime interaction, indicating change in activity will be greater for hypnotherapy. Minimum detectable effect size for the GroupXTime interaction is 0.7; power=0.8, alpha=0.05. Simple effects tests will be conducted to ensure randomization to treatment arm was successful. Similar analyses will be conducted to evaluate treatment effects on functional connectivity. Study size will be able to detect within-group differences between pre and post-treatment signal; minimal effect size of approximately 0.5, power=0.8, lower than the effect size of >3 in the pilot. Minimum effect size would be reached with a 15% decrement in anterior cingulate cortex to insula connectivity. For evoked activity investigators predict a main effect of time and a significant Group x Time interaction (change in functional connectivity will be greater for hypnotherapy relative to pharmacotherapy). Minimum detectable effect size for Group X Time interaction=0.7; power=0.8, alpha=0.05.This minimum effect size will be reached when between group differences in anterior cingulate cortex to insula connectivity are ≥ 30%. Baseline analysis: Controls vs. UUI at baseline. Regions of interest containing the insula and anterior cingulate cortex will be analyzed using two way ANCOVA with group as the between subject's factor. Pre-treatment β weights for bladder filling and urgency regressor effect on anterior cingulate cortex and insula signal among controls will be compared to UUI. Study size allows detection of between group differences with effect size >0.8, power=0.8, smaller than that in the pilot study.43 The effect size in the pilot (Cohen's d= 0.8-1.5) suggests the study will be adequately powered to reject the null hypothesis. Group-wise whole brain contrast will be performed using the same statistical model. False positives will be corrected at significance of p <.005,with a minimum cluster size of 32 voxels (p < 0.05) derived from 10,000 Monte Carlo simulations.80 Functional connectivity will be performed similarly to that used to analyze task brain activation.
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