Reduced-dose Botox for Urgency Incontinence Among Elder Females (RELIEF)

August 18, 2023 updated by: Anne C. Cooper, MD MA, Dartmouth-Hitchcock Medical Center

Reduced-dose onabotuLinumtoxinA for Urgency Incontinence Among Elder Females (RELIEF): A Randomized Controlled Comparative Effectiveness Trial With Embedded Qualitative and Costing Analyses

The purpose of this study is to study the treatment of urgency urinary incontinence (UUI), specifically among women 70 years and older, by comparing reduced versus standard dose of onabotulinumtoxinA (BTX; trade name BOTOX(c)) injection in the bladder.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this quadruple-masked, randomized-controlled study is to study the treatment of urgency urinary incontinence (UUI) specifically among older women with low- versus standard-dose of onabotulinumtoxinA (BTX) via: symptom-specific and health-related quality of life (QOL; Aim 1), patient-reported and clinical outcome measures including adverse events (Aim 2), qualitative experience with focused interviews (Aim 3) and cost burden and economic impact (Aim 4). This study is an active collaboration between researchers in Gynecology, Urology, and Geriatrics at Dartmouth Hitchcock Medical Center (DHMC) and at 5 other centers; University of Alabama (UAB), University of Pittsburgh (U Pitt), University of Texas Southwestern (UTSW), Kaiser Permanente of Southern California (KPSCP), and Oregon Health & Sciences University (OHSU). The investigators also have collaborators at Stanford University and University of Connecticut, though those sites are not recruiting participants.

Study Type

Interventional

Enrollment (Estimated)

376

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama - Birmingham
        • Contact:
        • Principal Investigator:
          • Isuzu Meyer, MD
        • Principal Investigator:
          • Tracey Wilson, MD
        • Sub-Investigator:
          • Holly Richter, MD
        • Sub-Investigator:
          • David Ellington, MD
        • Sub-Investigator:
          • Thomas Powell, MD
        • Sub-Investigator:
          • Gena Dunivan, MD
    • California
      • San Diego, California, United States, 92110
        • Recruiting
        • Kaiser Permanente Medical Group
        • Sub-Investigator:
          • Jasmine Tan-Kim, MD
        • Principal Investigator:
          • Shawn Menefee, MD
        • Sub-Investigator:
          • Kimberly Ferrante, MD
        • Sub-Investigator:
          • Tatiana Catanzarite, MD
        • Sub-Investigator:
          • Gouri Diwadkar, MD
        • Contact:
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03766
        • Recruiting
        • Dartmouth-Hitchcock Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Anne C Cooper, MD, MA
        • Sub-Investigator:
          • Elizabeth A Gormley, MD
        • Sub-Investigator:
          • Kris Strohbehn, MD
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University
        • Principal Investigator:
          • Sara Cichowski, MD
        • Sub-Investigator:
          • William T Gregory, MD
        • Sub-Investigator:
          • Ian Fields, MD
        • Sub-Investigator:
          • Kamran Sajadi, MD
        • Sub-Investigator:
          • Neesha Patel, MD
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Marcella Messerle-Forbes
        • Sub-Investigator:
          • Andrea O'Donnell
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Christopher Chermansky, MD
        • Sub-Investigator:
          • Megan Bradley, MD
        • Sub-Investigator:
          • Jocelyn Fitzgerald, MD
        • Sub-Investigator:
          • Mary Ackenbom, MD
        • Sub-Investigator:
          • Pamela Moalli, MD
        • Sub-Investigator:
          • Halina Zyczynski, MD
        • Sub-Investigator:
          • Lauren Giugale, MD
        • Sub-Investigator:
          • Amanda Artsen, MD
        • Sub-Investigator:
          • Sarah Napoe, MD
    • Texas
      • Dallas, Texas, United States, 75390
        • Not yet recruiting
        • University of Texas Southwestern Medical Center
        • Principal Investigator:
          • Ramy Goueli, MD
        • Sub-Investigator:
          • David Rahn, MD
        • Sub-Investigator:
          • Gary Lemack, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

70 years and older (Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult female at least 70 years old at date of enrollment
  2. Urge-predominant mixed urinary incontinence (urge>stress per the MESA questionnaire)
  3. On average 2 or more urgency or insensible incontinence episodes per day per patient report

  4. Refractory urinary urgency incontinence, defined as

    1. Persistent symptoms despite trial of one or more conservative treatments (e.g. behavioral therapy, physical therapy, home Kegel exercises); participants not required to have attempted first line therapies if deemed not feasible or appropriate by provider with input of participant/caregiver.
    2. Persistent symptoms despite the use of anticholinergic and/or beta-3 agonist medication; or inability to tolerate medication due to side effects, or has a contraindication to taking medication, or is unable to afford the cost of the medication.
  5. Currently not on an anticholinergic or beta-3 agonist medication or is willing to stop medication for 3 weeks prior to completing baseline bladder tally, with plan to remain off medication through duration of the study. Currently not actively using sacral neuromodulation therapy (either has not tried, or unit has been off for 4 weeks prior to baseline bladder tally and will remain turned off for the duration of the study). It is permissible for participants to continue self-led conservative therapies during participation in the study, including Kegel exercises, avoidance of bladder irritants, and urge suppression.
  6. Willing and able to complete all study-related items, with assistance of caregiver(s) if needed.
  7. Demonstrates awareness of possible need for catheterization in event of post-injection urinary retention & acknowledges risks of catheterization. Participant does not need to demonstrate ability to perform self-catheterization.
  8. Grossly neurologically normal on exam and no gross systemic neurologic conditions believed to affect urinary function. Patients with a diagnosis of Parkinson's disease or diabetes may be eligible provided they have a grossly normal neurologic exam and otherwise fulfill the inclusion/exclusion criteria.

Exclusion Criteria:

  1. Lack of capacity to provide consent. Will be assessed if needed per judgment of the site PI and study staff, with use of optional questionnaire.
  2. Baseline persistently elevated post-void residual [PVR] (>150mL on 2 occasions in the 6 weeks prior to enrollment). If the PVR was obtained via bladder scanner with measurements differing by more than 100mL, or if there is concern about the accuracy of the scanner, it will be confirmed via catheterization which will be considered the gold standard.
  3. Need for BTX injection to take place in the Operating Room or under sedation. (Of note, for repeat injection under the protocol, patients may have OR injection if indicated due to pain with initial BTX injection.)
  4. Previous treatment with intravesical BTX in the last 12 months or use of sacral neuromodulation therapy within the past 4 weeks (unit may remain implanted, but should remain off for duration of the study).
  5. Untreated symptomatic urinary tract infection (UTI). Eligible once UTI treatment complete and symptoms resolved.
  6. Known bladder abnormality, including current or prior bladder malignancy, carcinoma in situ or untreatable cystitis (e.g. eosinophilic cystitis); prior major bladder surgery that would alter the detrusor muscle, such as augmentation cystoplasty; or hematuria that has not been evaluated.
  7. Neurogenic detrusor overactivity or neurologic disease that may impact bladder function, including stroke, multiple sclerosis, peripheral neuropathy, spinal cord injury. Conditions such as Parkinson's disease and diabetes are acceptable provided normal bladder emptying and grossly normal neurologic function.
  8. Concurrent BTX use for other indication, participants cannot exceed 300 units BTX in a 3 month period. Participants who may have conflict between study BTX administration and administration for other purposes may be excluded from participation if there is concern that study drug administration will be compromised. Concurrent use of BTX for another indication that would not exceed 300 units in a 3 month period, or that can have time of administration of the other BTX adjusted to avoid excessive dose, is acceptable; for instance, for migraines.
  9. Greater than stage 2 pelvic floor prolapse, uncorrected or persistent despite pessary use (leading edge of prolapse not greater than 1cm beyond the hymen). Ongoing pessary use is permissible. Patients may have had a prior repair for pelvic organ prolapse. (see chart review of recent exam or perform brief exam while collecting post-void residual)
  10. Planned prolapse or stress incontinence surgery; would defer enrollment to >3 months post-operative.
  11. Allergy or intolerance to lidocaine or BTX.
  12. Participation in another research study that could conflict with the RELIEF study, in estimation of the site PI.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Botox: Standard dose
The standard dose of 100 units of botox will be injected into the bladder.
Drug: Botox 100 Unit Injection
Participants will be randomized to either receive a standard does (100 units) or low dose (50 units) of botox one time.If a particParticipants will be randomized to either receive a standard dose (100 units) or low dose (50 units) of onabotulinumtoxinA. If a participant has decreased symptom relief, after 3 months post injection, they may receive repeat injection up to twice during the 12 month follow-up period.
Other Names:
  • OnabotulinumtoxinA 100 Unit
Experimental: Botox: Low dose
A lower dose of 50 units of botox will be injected into the bladder.
Drug: Botox 50 Unit Injection
Participants will be randomized to either receive a standard dose (100 units) or low dose (50 units) of onabotulinumtoxinA. If a participant has decreased symptom relief, after 3 months post injection, they may receive repeat injection up to twice during the 12 month follow-up period.
Other Names:
  • OnabotulinumtoxinA 50 Unit Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in symptom specific quality of life and bother over time.
Time Frame: Baseline, monthly post-injection through 12 months post-injection; primary outcome is at 3 months post-injection.
The Overactive bladder questionnaire (OABq-SF), is a validated and reliable patient-centered quality of life questionnaire. The OABq-SF is based on a continuous sore of 0-100, with higher score translating to greater bother.
Baseline, monthly post-injection through 12 months post-injection; primary outcome is at 3 months post-injection.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Global Symptom Improvement
Time Frame: Baseline,3, 6, & 12 months post injection
Participants will be asked to complete the Patient Global Impression of Improvement (PGI-I) scale. The PGI-I scale is a one item assessment with responses ranging from "very much better" to "very much worse".
Baseline,3, 6, & 12 months post injection
Procedural discomfort and adverse events
Time Frame: Day of injection and monthly through 12 months
Urinary retention, post-void residual & duration of voiding dysfunction; urinary tract infection, unscheduled clinic/emergency department visits and any adverse events assessed using the Clavien-Dindo scale,which has been validated for use in urology setting.
Day of injection and monthly through 12 months
Qualitative experience of BTX treatment and adverse events
Time Frame: Baseline & 3 months post injection
Using novel focused interview for a subset of participants. Participants will be interviewed before injection and 3 months post injection.
Baseline & 3 months post injection
Survey of economic burden
Time Frame: Baseline, 3 & 12 months. Results will be compared at the end of the 12 months.
Incontinence Resource Use Questionnaire measures the amount of use of various incontinence products. Questions include the number of incontinence protection items used per week.
Baseline, 3 & 12 months. Results will be compared at the end of the 12 months.
Symptom severity
Time Frame: Baseline, 3, 6, & 12 months post injection. Results will be compared at the end of the 12 months.
Urogential Distress Inventory (UDI-6). The UDI-6 has a cut off score of 33.33 to distinguish women who are symptomatic versus asymptomatic. UDI-6 scores that are greater than 33.33 indicated higher distress caused by urinary incontinence symptoms.
Baseline, 3, 6, & 12 months post injection. Results will be compared at the end of the 12 months.
Symptom bother
Time Frame: Baseline, 3, 6, & 12 months post injection. Results will be compared at the end of the 12 months.
Incontinence impact questionnaire (IIQ). The IIQ has a cut off score of 9.52. This score distinguish women who are symptomatic and asymptomatic.
Baseline, 3, 6, & 12 months post injection. Results will be compared at the end of the 12 months.
Change in number of urgency urinary incontinence (UUI) episodes per day.
Time Frame: Baseline, and 1, 3, and 6 months post injection
Participants will keep a bladder tally for 3 days and results will be compared from baseline to 1, 3, and 6 months post injected to determine if there has been a change in the number of urgency urinary incontinence episodes.
Baseline, and 1, 3, and 6 months post injection
Goal setting and attainment
Time Frame: Baseline & 3 months post injection.
Participants will express 3-5 goals and goal attainment will be assessed with the Patient Global Impression of Improvement Survey (PGI-I Scale). The PGI-I scale is a one item assessment with responses ranging from "very much better" to "very much worse".
Baseline & 3 months post injection.
Change in general health-related quality of life as measure by the Health Utility Index-3
Time Frame: Baseline, 3 6 and 12 months
Participants will complete the Health Utilities Index (HUI). The HUI measure health status, reporting health-related quality of life, and producing utility scores. The score ranges from 0.00 (dead) to 1.00 (perfect health).
Baseline, 3 6 and 12 months
Depression
Time Frame: Baseline, 3, 6 and 12 months post injection. Results will be compared at the end of the 3 month post injection.
Patient Health Questionnaire-9 (PHQ-9) is a 10 item scale with scores ranging from 1(minimal depression) to 27 (severe depression).
Baseline, 3, 6 and 12 months post injection. Results will be compared at the end of the 3 month post injection.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dartmouth-Hitchcock Medical Center

Collaborators

Patient-Centered Outcomes Research Institute
University of Alabama at Birmingham
University of Pittsburgh
Oregon Health and Science University
Stanford University
University of Texas
Dartmouth College
Kaiser Permanente
University of Connecticut

Investigators

  • Principal Investigator: Anne C Cooper, MD, Dartmouth-Hitchcock Medical Center
  • Principal Investigator: Elizabeth A Gormley, MD, Dartmouth-Hitchcock Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 12, 2023

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

August 19, 2022

First Submitted That Met QC Criteria

August 19, 2022

First Posted (Actual)

August 23, 2022

Study Record Updates

Last Update Posted (Actual)

August 21, 2023

Last Update Submitted That Met QC Criteria

August 18, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY02001338

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Yes, per PCORI data sharing policy. Details TBD.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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