Reduced-dose Botox for Urgency Incontinence Among Elder Females

NCT05512039 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY02001338
• Study Type: interventional
• Target: 376
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Overactive Bladder; Urgency Urinary Incontinence; Urinary Incontinence in Old Age

Keywords

Urinary Incontinence; Urgency Urinary Incontinence; Overactive Bladder

Outcome Measures

Primary Outcomes (1)

• Change in symptom specific quality of life and bother over time.

  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 Outcomes (10)

• Symptom severity

  Baseline, 3, 6, & 12 months post injection. Results will be compared at the end of the 12 months.

• Symptom bother

  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.

  Baseline, and 1, 3, and 6 months post injection

• Change in Global Symptom Improvement

  Baseline,3, 6, & 12 months post injection

• Goal setting and attainment

  Baseline & 3 months post injection.

Study Arms (2)

Botox: Standard dose

ACTIVE COMPARATOR

The standard dose of 100 units of botox will be injected into the bladder.

Drug: Botox 100 Unit Injection

Botox: Low dose

EXPERIMENTAL

A lower dose of 50 units of botox will be injected into the bladder.

Drug: Botox 50 Unit Injection

Interventions

Botox 50 Unit Injection DRUG

Participants will be randomized to either receive a standard dose (100 units) or reduced dose (50 units) of onabotulinumtoxinA. If a participant has decreased symptom relief they may receive repeat treatment up to twice during the 12 month follow-up period, with minimum 4 month intervals between treatments.

Also known as: OnabotulinumtoxinA 50 Unit Injection

Botox: Low dose

Botox 100 Unit Injection DRUG

Participants will be randomized to either receive a standard dose (100 units) or reduced dose (50 units) of onabotulinumtoxinA. If a participant has decreased symptom relief they may receive repeat injection up to twice during the 12 month follow-up period, with minimum 4 month intervals between treatments.

Also known as: OnabotulinumtoxinA 100 Unit

Botox: Standard dose

Eligibility Criteria

• Age: 70 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Adult female at least 70 years old at date of enrollment
• Urgency urinary incontinence (urge incontinence \> stress incontinence per screening criteria)
• On average 2 or more urgency or insensible incontinence episodes per day per patient report
• Refractory urinary urgency incontinence, defined as
• 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.
• 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.
• 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.
• Willing and able to complete all study-related items, with assistance of caregiver(s) if needed.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.)
• 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).
• Untreated symptomatic urinary tract infection (UTI). Eligible once UTI treatment complete and symptoms resolved.
• 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.
• 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.
• 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.
• 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)
• Planned prolapse or stress incontinence surgery; would defer enrollment to \>3 months post-operative.
• Allergy or intolerance to lidocaine or BTX.
• Participation in another research study that could conflict with the RELIEF study, in estimation of the site PI.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• Patient-Centered Outcomes Research Institute: collaborator
• Dartmouth College: collaborator
• University of Alabama at Birmingham: collaborator
• University of Pittsburgh: collaborator
• University of Texas: collaborator
• Kaiser Permanente: collaborator
• Stanford University: collaborator
• University of Connecticut: collaborator
• University of Nebraska: collaborator
• Oregon Health and Science University: collaborator

Study Sites (7)

University of Alabama - Birmingham

Birmingham, Alabama, 35233, United States

Location

Kaiser Permanente Medical Group

San Diego, California, 92110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (8)

• Amundsen CL, Komesu YM, Chermansky C, Gregory WT, Myers DL, Honeycutt EF, Vasavada SP, Nguyen JN, Wilson TS, Harvie HS, Wallace D; Pelvic Floor Disorders Network. Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial. Eur Urol. 2018 Jul;74(1):66-73. doi: 10.1016/j.eururo.2018.02.011. Epub 2018 Feb 24.

  PMID: 29482936 BACKGROUND

• Gormley EA, Lightner DJ, Faraday M, Vasavada SP; American Urological Association; Society of Urodynamics, Female Pelvic Medicine. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol. 2015 May;193(5):1572-80. doi: 10.1016/j.juro.2015.01.087. Epub 2015 Jan 23.

  PMID: 25623739 BACKGROUND

• Drake MJ, Nitti VW, Ginsberg DA, Brucker BM, Hepp Z, McCool R, Glanville JM, Fleetwood K, James D, Chapple CR. Comparative assessment of the efficacy of onabotulinumtoxinA and oral therapies (anticholinergics and mirabegron) for overactive bladder: a systematic review and network meta-analysis. BJU Int. 2017 Nov;120(5):611-622. doi: 10.1111/bju.13945. Epub 2017 Aug 2.

  PMID: 28670786 BACKGROUND

• Coyne KS, Payne C, Bhattacharyya SK, Revicki DA, Thompson C, Corey R, Hunt TL. The impact of urinary urgency and frequency on health-related quality of life in overactive bladder: results from a national community survey. Value Health. 2004 Jul-Aug;7(4):455-63. doi: 10.1111/j.1524-4733.2004.74008.x.

  PMID: 15449637 BACKGROUND

• Monz B, Pons ME, Hampel C, Hunskaar S, Quail D, Samsioe G, Sykes D, Wagg A, Papanicolaou S. Patient-reported impact of urinary incontinence--results from treatment seeking women in 14 European countries. Maturitas. 2005 Nov 30;52 Suppl 2:S24-34. doi: 10.1016/j.maturitas.2005.09.005. Epub 2005 Nov 16.

  PMID: 16297579 BACKGROUND

• Furlong WJ, Feeny DH, Torrance GW, Barr RD. The Health Utilities Index (HUI) system for assessing health-related quality of life in clinical studies. Ann Med. 2001 Jul;33(5):375-84. doi: 10.3109/07853890109002092.

  PMID: 11491197 BACKGROUND

• Horsman J, Furlong W, Feeny D, Torrance G. The Health Utilities Index (HUI): concepts, measurement properties and applications. Health Qual Life Outcomes. 2003 Oct 16;1:54. doi: 10.1186/1477-7525-1-54.

  PMID: 14613568 BACKGROUND

• Yalcin I, Bump RC. Validation of two global impression questionnaires for incontinence. Am J Obstet Gynecol. 2003 Jul;189(1):98-101. doi: 10.1067/mob.2003.379.

  PMID: 12861145 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder, Overactive; Urinary Incontinence

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urination Disorders

Study Officials

• Anne C Cooper, MD, MA

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

• E A Gormley, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Assistant Professor

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: August 23, 2022
• Study Start: May 12, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (7)