Brain-Centered Therapy Versus Medication for Urgency Urinary Incontinence : Hypnotherapy Or Pharmacotherapy (Hyp-hOP)

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

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 Hypotheses: Among patients with urgency urinary incontinence (UUI), hypnotherapy will be non-inferior pharmacotherapy in diminishing UUI episodes. Hypnotherapy may be superior or may not differ from pharmacotherapy in diminishing symptoms or quality of life based on validated questionnaires and/or other diary parameters.

Study Overview

• Status: Completed
• Conditions: Urinary Incontinence, Urge
• Intervention / Treatment: Drug: Anticholinergic medications; Behavioral: Hypnotherapy

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)

Secondary Analyses:

• To determine whether hypnotherapy is at least as effective in treating UUI as pharmacotherapy comparing change in UUI episodes on voiding diary at 6 and 12 month follow-up
• To determine whether hypnotherapy differs from pharmacotherapy in treating UUI comparing change in questionnaire results and urinary frequency
• enrolled following administration of the Overactive Bladder (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. Study personnel performing data entry will be masked to participants' treatment. Masking participants to treatment is not feasible. Participants will be followed at 2,6 & 12 months. Measurements will be performed before treatment, following completion of treatment visits (approximately 8 weeks), and at 6 and 12 months. Primary analysis will be intention to treat. Exploratory analyses of secondary outcomes will also be performed.

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 with administration of study questionnaires, demographic and past medical history administration forms, Pelvic Organ Prolapse Quantitation (POP-Q) exam & hypnotic susceptibility testing scheduled. Pariticipants undergo hypnotic susceptibility testing prior to randomization. Participants randomized to treatment and contacted, treatments arranged. Hypnotherapy group: undergo weekly treatments over 8 weeks. Pharmacotherapy group: weekly counseling sessions over 8 week: Following hypnotherapy or medication counseling completion, f/u voiding diaries collected & study questionnaires administered. One of two long acting anti-cholinergic medications offered (Long acting Tolterodine or Extended Release Oxybutynin or equivalent generic substitutes).

6 & 12 month follow-up: Pharmacotherapy subjects receive medications for 1 year and Hypnotherapy subjects encouraged to continue self-hypnosis for 1 year with assistance of audio-recordings, with 1 optional hypnotherapy session between 6-12 months..

Participants informed pharmacotherapy & hypnotherapy sessions are audio-recorded and reviewed ensuring manual of procedures are followed.

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:(For randomized trial)

1. Non-pregnant English-speaking women
2. 18 yo or older
3. Overactive Bladder (OAB) Awareness scores ≥ 8
4. 3 UUI episodes/week for ≥ 3 months

Exclusion Criteria: (For Randomized trial)

1. Women with a history of neurologic diseases such as Multiple Sclerosis, Parkinson's disease, stroke, or dementia
2. History of schizophrenia or untreated bipolar disorder or current drug or alcohol dependence
3. Women who have taken anticholinergic medications for UUI within the last 3 weeks (women who have taken anti-cholinergics for UUI but discontinued them > than 3 weeks ago may participate in the study) or have a sacral neuromodulator in place to treat UUI or have received Onabotulinum toxin A in the last 12 months to treat UUI
4. Contraindications to anticholinergic medications (untreated narrow angle glaucoma, significant urinary retention or gastric retention)
5. Pregnant women or lactating women, women who plan to become pregnant in the next year, or pre-menopausal women unwilling to use contraception if engaging in sexual relations during the year of study participation (hysterectomy is considered to be a form of contraception)
6. Untreated urinary tract infection
7. Prolapse which extends past the hymen (POP-Q points of ≥ 1+) which may be responsible for UUI symptoms
8. Women who cannot keep the majority of the study therapy appointments or those without reliable contact phone numbers or methods of communication with the study personnel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anticholinergic medications; Either of two standard, long acting anti-cholinergic medications (Long acting Tolterodine or Extended Release Oxybutynin)will be given. Subjects receive 8 weeks of medication counseling in conjunction with the medications. Medications will be continued for 1 year.	Drug: Anticholinergic medications; The study will use either of two standard, long acting anti-cholinergic medications and dosages. Pharmacotherapy counseling sessions will also be administered over 8 weeks by trained research personnel. Pharmacotherapy counseling sessions will be audio-recorded and one or more sessions will be reviewed by study personnel to ensure that the medication counselor administers the sessions in a standardized fashion. Pill counts will be performed at the conclusion of the 8 weeks of pharmacotherapy counseling. Subjects will be provided the medication for 1 year.; Other Names: Tolterodine (Detrol LA or equivalent generic); Oxybutynin (Ditropan Extended Release or equivalent generic)
Active Comparator: Hypnotherapy; Subjects will receive approximately weekly hypnotherapy sessions over 8 weeks and will receive/download digital recordings for home practice. Subjects will be encouraged to practice self-hypnosis +/or listen to their recordings for 1 year.	Behavioral: Hypnotherapy; Hypnotherapy will be administered approximately weekly over 8 weeks by certified, trained clinical hypnotherapists. Sessions will be audio-recorded and one or more sessions will be reviewed by study personnel to ensure that the hypnotherapist administers the hypnotherapy session in a standardized fashion.Subjects will receive or download a digital recording specially prepared for them to for home practice of hypnotherapy sessions.Following the 8 weeks of therapy, subjects will be encouraged to continue to practice self-hypnosis and/or listen to their home practice digital recording and this practice will be tracked for the 1 year duration of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Urgency Urinary Incontinence Episodes	Percent change in UUI episodes from baseline to 2 months with comparison made between hypnotherapy & pharmacotherapy	Baseline and 2 month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Urgency Urinary Incontinence Episodes	Differences comparing hypnotherapy to pharmacotherapy percent change in median UUI episodes	6 months
Percent Change in Urgency Urinary Incontinence Episodes	Percent change in median UUI episodes from baseline to 12 months with comparison made between hypnotherapy & pharmacotherapy	12 months
Overactive Bladder Questionnaire Short Form Symptom Bother	Overactive Bladder Questionnaire Short Form symptom bother Scale. Sub-Scale range 0-100. Higher numbers are worse (more bother) and lower numbers are better (less bother)	2 months
Overactive Bladder Questionnaire Short Form Symptom Bother	Overactive Bladder Questionnaire Short Form symptom bother. Sub-scale range 0-100. Higher numbers are worse (more bother) and lower numbers are better (less bother)	6 months
Overactive Bladder Questionnaire Short Form Symptom Bother	Overactive Bladder Questionnaire Short Form symptom bother. Sub-scale range 0-100. Higher numbers are worse (more bother) and lower numbers are better (less bother)	12 months
Overactive Bladder Questionnaire Short Form Quality of Life	Overactive Bladder questionnaire-Short Form Quality of Life. Higher scores are better (better quality of life) and lower scores are worse (poorer quality of life). sub-score range 0-100.	2 months
Overactive Bladder Questionnaire Short Form Quality of Life	Overactive Bladder questionnaire Short Form Quality of Life. Higher scores are better (better quality of life) and lower scores are worse (poorer quality of life). sub-scale score range 0-100.	6 months
Overactive Bladder Questionnaire Short Form Quality of Life	Overactive Bladder questionnaire-Short Form Quality of Life. Higher scores are better (higher quality of life) and lower scores are worse (poorer quality of life). score range 0-100.	12 months
Voids on Bladder Diary	Total Number of voids on 3-day bladder diary.	2 months
Voids on Bladder Diary	number of voids on 3-day bladder diary	6 months
Voids on Bladder Diary	number of voids on 3-day bladder diary	12 months

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Yuko Komesu, MD, University of New Mexcio Health Science Center

Publications and helpful links

General Publications

• Coyne KS, Matza LS, Kopp Z, Abrams P. The validation of the patient perception of bladder condition (PPBC): a single-item global measure for patients with overactive bladder. Eur Urol. 2006 Jun;49(6):1079-86. doi: 10.1016/j.eururo.2006.01.007. Epub 2006 Jan 24.
• Coyne K, Revicki D, Hunt T, Corey R, Stewart W, Bentkover J, Kurth H, Abrams P. Psychometric validation of an overactive bladder symptom and health-related quality of life questionnaire: the OAB-q. Qual Life Res. 2002 Sep;11(6):563-74. doi: 10.1023/a:1016370925601.
• Burgio KL, Locher JL, Goode PS, Hardin JM, McDowell BJ, Dombrowski M, Candib D. Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial. JAMA. 1998 Dec 16;280(23):1995-2000. doi: 10.1001/jama.280.23.1995.
• Komesu YM, Ketai LH, Mayer AR, Teshiba TM, Rogers RG. Functional MRI of the Brain in Women with Overactive Bladder: Brain Activation During Urinary Urgency. Female Pelvic Med Reconstr Surg. 2011;17(1):50-54. doi: 10.1097/SPV.0b013e3182065507.
• Komesu YM, Sapien RE, Rogers RG, Ketai LH. Hypnotherapy for treatment of overactive bladder: a randomized controlled trial pilot study. Female Pelvic Med Reconstr Surg. 2011 Nov;17(6):308-13. doi: 10.1097/SPV.0b013e31823a08d9.
• Sandvik H, Seim A, Vanvik A, Hunskaar S. A severity index for epidemiological surveys of female urinary incontinence: comparison with 48-hour pad-weighing tests. Neurourol Urodyn. 2000;19(2):137-45. doi: 10.1002/(sici)1520-6777(2000)19:23.0.co;2-g.
• Coyne KS, Zyczynski T, Margolis MK, Elinoff V, Roberts RG. Validation of an overactive bladder awareness tool for use in primary care settings. Adv Ther. 2005 Jul-Aug;22(4):381-94. doi: 10.1007/BF02850085.
• Ketai LH, Komesu YM, Schrader RM, Rogers RG, Sapien RE, Dodd AB, Mayer AR. Mind-body (hypnotherapy) treatment of women with urgency urinary incontinence: changes in brain attentional networks. Am J Obstet Gynecol. 2021 May;224(5):498.e1-498.e10. doi: 10.1016/j.ajog.2020.10.041. Epub 2020 Oct 26.
• Komesu YM, Schrader RM, Rogers RG, Sapien RE, Mayer AR, Ketai LH. Hypnotherapy or medications: a randomized noninferiority trial in urgency urinary incontinent women. Am J Obstet Gynecol. 2020 Feb;222(2):159.e1-159.e16. doi: 10.1016/j.ajog.2019.08.025. Epub 2019 Aug 23.

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2013
• Primary Completion (Actual): October 27, 2017
• Study Completion (Actual): October 27, 2017

Study Registration Dates

• First Submitted: April 8, 2013
• First Submitted That Met QC Criteria: April 8, 2013
• First Posted (Estimate): April 11, 2013

Study Record Updates

• Last Update Posted (Actual): April 23, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Hypnosis; Female Urogenital Diseases; Anticholinergics; Mind-Body Therapy
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Elimination Disorders; Urinary Incontinence; Enuresis; Urinary Incontinence, Urge; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Agents; Urological Agents; Oxybutynin; Tolterodine Tartrate; Cholinergic Antagonists
• Other Study ID Numbers: 09-314; 1R01AT007171-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The information will be shared with other researchers upon their request. Our IRB required that we re-consent participants in order to make their data available to others. We can only share the information available on participants who signed these additional consents.
• IPD Sharing Time Frame: 6 months after manuscript for the primary outcome is accepted for publication. Anticipated time for manuscript acceptance July 2019. Anticipated availability 3-5 years.
• IPD Sharing Access Criteria: Dr. Komesu and Dr. Ketai will review requests. Access criteria includes de-identified dataset (including de-identification of dates of visit as this may be interpreted as a potential identifier) of those who consented to have data shared. Data for secondary manuscripts in progress by PIs will be shared only after PIs publish said data 6 months post-publication.
• IPD Sharing Supporting Information Type: Study Protocol