RELIEF: Reduced-dose Botox for Urgency Incontinence Among Elder Females: A Mixed-methods Randomized Controlled Trial

Sponsor

Dartmouth-Hitchcock Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05512039

Collaborator

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

350

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 low-and standard dose of onabotulinumtoxinA (BTX; trade name BOTOX(c)) injection in the bladder.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder Urinary Incontinence in Old Age Urgency Urinary Incontinence	Drug: Botox 50 Unit Injection Drug: Botox 100 Unit Injection	Phase 1/Phase 2

Detailed Description

The purpose of this mixed methods, 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). We also have collaborators at Stanford University and University of Connecticut, though those sites are not recruiting participants.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

350 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Reduced-dose onabotuLinumtoxinA for Urgency Incontinence Among Elder Females (RELIEF): A Mixed Methods Randomized Controlled Trial

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Jan 1, 2027

Arms and Interventions

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 participant has decreased symptom relief, after 3 months post injection, they may receive repeat injection up to every 4 months. 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 does (100 units) or low dose (50 units) of botox one time.If a participant has decreased symptom relief, after 3 months post injection, they may receive repeat injection up to every 4 months. Other Names: OnabotulinumtoxinA 50 Unit Injection

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 participant has decreased symptom relief, after 3 months post injection, they may receive repeat injection up to every 4 months.

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

Other Names:

OnabotulinumtoxinA 50 Unit Injection

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Change in symptom severity over time. [Baseline, 3, 6, & 12 months post injection. Results will be compared at the end of the 12 months.]
Urinary 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.
Incontinence Impact Questionnaire - short form (IIQ-7) [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.
Urogenital Distress Inventory - short form (UDI-6) [Baseline, 3, 6, & 12 months post injection. Results will be compared at the end of the 12 months.]
Urinary Distress Inventory (UDI-6). The UDI-6 has a cut off score of 33.33 and this score distinguishs women who are symptomatic and asymptomatic. UDI-6 scores that are greater than 33.33 indicated higher distress caused by urinary incontinence symptoms.
Change in number of urgency urinary incontinence (UUI) episodes per day. [1, 3, and 6 months post injection]
Participants will keep a bladder tally and pad count for 3 days and results will be compared from 1, 3, and 6 months post injected to determine if there has been a change in the number of urgency urinary incontinence.
Change in Global Symptom Improvement [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".
Change in goal setting and attainment [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".
Change in health-related quality of life as measure by the Health Utility Index-3 [Baseline and then monthly through 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).
Depression [Baseline & 3 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).
Procedural discomfort and adverse events [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.
Qualitative experience of BTX treatment and adverse events [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.
Survey of economic burden [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult female at least 70 years old
Urge-predominant mixed urinary incontinence (urge>stress per the Medical, Epidemiological, and Social Aspects of Aging questionnaire) (MESA questionnaire89).
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 diary 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 and interviews, 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.
Grossly neurologically normal on exam and no gross systemic neurologic conditions believed to affect urinary function.

Exclusion Criteria:

Dementia or severe cognitive impairment
Baseline persistently elevated post-void residual [PVR] (>150mL on 2 occasions in the 6 weeks prior to enrollment). If the post-void residual (PVR) was obtained via bladder scanner with measurements differing by more than 100mL, it will be confirmed via catheterization which will be considered the gold standard.
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).
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.
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.
Greater than stage 2 pelvic floor prolapse, uncorrected or persistent despite pessary use. Ongoing pessary use is permissible.
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.

Contacts and Locations

Locations

No locations specified.

Investigators

Principal Investigator: Anne C Cooper, MD, Dartmouth-Hitchcock Medical Center
Principal Investigator: E Ann Gormley, MD, Dartmouth-Hitchcock Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Anne C. Cooper, MD MA, Principal Investigator, Assistant Professor, Dartmouth-Hitchcock Medical Center

ClinicalTrials.gov Identifier:

NCT05512039

Other Study ID Numbers:

STUDY02001338

First Posted:

Aug 23, 2022

Last Update Posted:

Aug 23, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Anne C. Cooper, MD MA, Principal Investigator, Assistant Professor, Dartmouth-Hitchcock Medical Center

Urinary Incontinence

Urgency Urinary Incontinence

Overactive Bladder

Additional relevant MeSH terms: