Standard Injections Versus Reduced Injections for Intravesical onabotulinumtoxinA Treatment of Overactive Bladder

NCT04020510 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 2019-0232
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

Brief Summary

OnabotulinumtoxinA is an effective treatment for both idiopathic and neurogenic overactive bladder and was FDA approved for this indication in 2013. The standard technique for injecting onabotulinumtoxinA into the detrusor is mixing 100 units of onabotulinumtoxinA into 10mL of injectable normal saline and injecting 20 sites with 0.5mL in the posterior wall of hte bladder for idiopathic overactive bladder and mixing 200 units into 30mL and injecting 30 sites with 1mL for neurogenic overactive bladder. The purpose of this study is to compare the efficacy of a technique using a reduced number of injections with the same dosage of onabotulinumtoxinA to the standard technique. The hypothesis is that the reduced technique will not be inferior in terms of efficacy as the standard technique and that there will be a lower incidence of urinary tract infections and urinary retention requiring catheterization post-procedure.

Conditions

Overactive Bladder

Outcome Measures

Primary Outcomes (7)

• Mean change from baseline in overactive bladder symptom severity and health related quality of life scores on the overactive bladder questionnaire short form

  The overactive bladder questionnaire short form is a validated questionnaire assessing both symptoms and quality of life related to overactive bladder. The survey has two subscales, a health related quality of life scale and a symptom severity scale. Each subscale is scored separately with a range of 0 to 100. For health related quality of life a score of 0 indicates worst quality of life and 100 indicating best quality of life. For symptom severity, the scores also range from 0 to 100 but with higher scores indicating greater symptom severity and lower scores less symptom severity.

  4-12 weeks post-procedure

• Mean change from baseline in overactive bladder symptom severity and health related quality of life scores on the overactive bladder questionnaire short form

  The overactive bladder questionnaire short form is a validated questionnaire assessing both symptoms and quality of life related to overactive bladder. The survey has two subscales, a health related quality of life scale and a symptom severity scale. Each subscale is scored separately with a range of 0 to 100. For health related quality of life a score of 0 indicates worst quality of life and 100 indicating best quality of life. For symptom severity, the scores also range from 0 to 100 but with higher scores indicating greater symptom severity and lower scores less symptom severity.

  6-9 months post-procedure

• Mean change from baseline in overactive bladder symptoms on the International Consultation on Incontinence Questionnaire short form

  The International Consultation on Incontinence Questionnaire short form is a validated questionnaire assessing symptoms of overactive bladder and effect on quality of life. The scores range from 0 to 21 with higher scores indicating worse symptom severity and effect on quality of life.

  4-12 weeks post-procedure

• Mean change from baseline in overactive bladder symptoms on the International Consultation on Incontinence Questionnaire short form

  The International Consultation on Incontinence Questionnaire short form is a validated questionnaire assessing symptoms of overactive bladder and effect on quality of life. Scores range from 0 to 21 with higher scores indicating greater symptom severity.

  6-9 months post-procedure

• Mean change from baseline in overactive bladder symptoms assessed with the Patient Global Impression of Severity and Improvement scores

  The Patient Global Impression of Severity and Patient Global Impression of Improvement scores are validated single question surveys that assess patients' impression of the severity of their illness prior to treatment intervention and the degree of improvement following treatment intervention. The Patient Global Impression of Severity is a 4 point Likert scale ranging from 1 to 4 with 1 being normal and 4 being severe symptoms (mild and moderate completing the range of scores). The Patient Global Impression of Improvement is a 7 point Likert scale with 1 being very much better and 7 being very much worse (much better, a little better, no change, a little worse, and much worse completing the range of scores).

  baseline, 4-12 weeks post-procedure and 6-9 months post-procedure

• Mean change from baseline in overactive bladder symptoms assessed with the Patient Global Impression of Severity and Improvement scores

  The Patient Global Impression of Severity and Patient Global Impression of Improvement scores are validated single question surveys that assess patients' impression of the severity of their illness prior to treatment intervention and the degree of improvement following treatment intervention. The Patient Global Impression of Severity is a 4 point Likert scale ranging from 1 to 4 with 1 being normal and 4 being severe symptoms (mild and moderate completing the range of scores). The Patient Global Impression of Improvement is a 7 point Likert scale with 1 being very much better and 7 being very much worse (much better, a little better, no change, a little worse, and much worse completing the range of scores).

  4-12 weeks post-procedure

• Mean change from baseline in overactive bladder symptoms and incontinence episodes using patient reported pad counts and episodes of nocturia

  Number of pads used for urge incontinence and nocturia episodes are frequent metrics used for assessing efficacy of overactive bladder treatments

  6-9 months post-procedure

Secondary Outcomes (3)

• Incidence of urinary tract infection

  1 day to 12 weeks post-procedure

• Incidence of urinary retention requiring intermittent catheterization

  2-6 weeks post-procedure

• Mean change in pain from baseline following intradetrusor onabotulinumtoxinA injection using visual analog scale

  immediately post-procedure

Study Arms (2)

Standard Injections

ACTIVE COMPARATOR

For idiopathic overactive bladder, 100 units of onabotulinumtoxinA mixed in 10mL of injectable saline injected in 20 sites with 0.5mL per injection along the posterior wall of the bladder above the trigone. For neurogenic overactive bladder, 200 units of onabotulinumtoxinA mixed in 30mL of injectable saline injected in 30 sites with 1mL per injection along the posterior wall of the bladder above the trigone.

Drug: onaBoNT-A

Reduced Injections

EXPERIMENTAL

For idiopathic overactive bladder, 100 units of onabotulinumtoxinA mixed in 10mL of injectable saline injected in 5 sites with 2mL per injection in an "X" configuration on posterior wall of the bladder above the trigone. For neurogenic overactive bladder, 200 units of onabotulinumtoxinA mixed in 10mL of injectable saline injected in 5 sites with 2mL per injection in an "X" configuration on posterior wall of the bladder above the trigone.

Drug: onaBoNT-A

Interventions

onaBoNT-A DRUG

Intradetrusor onabotulinumtoxinA in either the standard number of injections or a reduced number of injections

Also known as: Botox

Reduced Injections; Standard Injections

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or Females ≥ 18 years of age
• Predominant complaint of urinary urgency, urinary frequency or urge incontinence
• Failed at least one medication (inadequate or poorly tolerated response) or behavior modification technique (timed voiding, pelvic floor physical therapy, etc.), or decline such interventions
• Willingness to perform self-catheterization in the event of symptomatic urinary retention
• Ability to follow study instructions and likely to complete all required follow-up

You may not qualify if:

• Concurrent use of oral medications for treatment of OAB (anticholinergics or beta 3 agonists).
• Post void residual volume \> 200 ml
• Symptomatic prolapse \> POP-Q (Pelvic Organ Prolapse Quantification) stage 2 or greater that is untreated
• Evidence of active UTI (bladder infection)
• Any previous use of intradetrusor botulinum toxin (onabotulinumtoxinA or abobotulinumtoxinA) within the preceding 6 months
• Use of \>/= 400 units bontulinum toxin in the preceding 3months in other areas of the body
• Procedure performed in the main operating room (not outpatient setting)
• Concurrent diagnosis of interstitial cystitis/painful bladder syndrome
• Females who are pregnant or planning a pregnancy during the study or who think that they may be pregnant at the start of the study, or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study.
• Any medical condition that may put the subject at increased risk with exposure to botulinum-A toxin, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis/motor neuron disease, neuropathy, renal stones, or any other disorder that might interfere with neuromuscular function
• Known allergy or sensitivity to any of the components of onabotulinumtoxinA
• Concurrent participation in another investigational drug or device study that could impact the results
• Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study

Sponsors & Collaborators

• Walter Reed National Military Medical Center: lead

Study Sites (1)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

RECRUITING

Related Publications (14)

• Avallone MA, Sack BS, El-Arabi A, Guralnick ML, O'Connor RC. Less is more-A pilot study evaluating one to three intradetrusor sites for injection of OnabotulinumtoxinA for neurogenic and idiopathic detrusor overactivity. Neurourol Urodyn. 2017 Apr;36(4):1104-1107. doi: 10.1002/nau.23052. Epub 2016 Jun 10.

  PMID: 27283922 BACKGROUND

• Lopez Ramos H, Torres Castellanos L, Ponce Esparza I, Jaramillo A, Rodriguez A, Moreno Bencardino C. Management of Overactive Bladder With OnabotulinumtoxinA: Systematic Review and Meta-analysis. Urology. 2017 Feb;100:53-58. doi: 10.1016/j.urology.2016.10.026. Epub 2016 Oct 24.

  PMID: 27789302 BACKGROUND

• Sirls LT, Tennstedt S, Brubaker L, Kim HY, Nygaard I, Rahn DD, Shepherd J, Richter HE. The minimum important difference for the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form in women with stress urinary incontinence. Neurourol Urodyn. 2015 Feb;34(2):183-7. doi: 10.1002/nau.22533. Epub 2013 Nov 23.

  PMID: 24273137 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

• Visco AG, Brubaker L, Richter HE, Nygaard I, Paraiso MF, Menefee SA, Schaffer J, Lowder J, Khandwala S, Sirls L, Spino C, Nolen TL, Wallace D, Meikle SF; Pelvic Floor Disorders Network. Anticholinergic therapy vs. onabotulinumtoxina for urgency urinary incontinence. N Engl J Med. 2012 Nov 8;367(19):1803-13. doi: 10.1056/NEJMoa1208872. Epub 2012 Oct 4.

  PMID: 23036134 BACKGROUND

• Coyne KS, Matza LS, Thompson CL, Kopp ZS, Khullar V. Determining the importance of change in the overactive bladder questionnaire. J Urol. 2006 Aug;176(2):627-32; discussion 632. doi: 10.1016/j.juro.2006.03.088.

  PMID: 16813906 BACKGROUND

• Ramirez-Castaneda J, Jankovic J, Comella C, Dashtipour K, Fernandez HH, Mari Z. Diffusion, spread, and migration of botulinum toxin. Mov Disord. 2013 Nov;28(13):1775-83. doi: 10.1002/mds.25582. Epub 2013 Jul 18.

  PMID: 23868503 BACKGROUND

• Coelho A, Cruz F, Cruz CD, Avelino A. Spread of onabotulinumtoxinA after bladder injection. Experimental study using the distribution of cleaved SNAP-25 as the marker of the toxin action. Eur Urol. 2012 Jun;61(6):1178-84. doi: 10.1016/j.eururo.2012.01.046. Epub 2012 Feb 1.

  PMID: 22306320 BACKGROUND

• Karsenty G, Denys P, Amarenco G, De Seze M, Game X, Haab F, Kerdraon J, Perrouin-Verbe B, Ruffion A, Saussine C, Soler JM, Schurch B, Chartier-Kastler E. Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. Eur Urol. 2008 Feb;53(2):275-87. doi: 10.1016/j.eururo.2007.10.013. Epub 2007 Oct 16.

  PMID: 17988791 BACKGROUND

• Liao CH, Chen SF, Kuo HC. Different number of intravesical onabotulinumtoxinA injections for patients with refractory detrusor overactivity do not affect treatment outcome: A prospective randomized comparative study. Neurourol Urodyn. 2016 Aug;35(6):717-23. doi: 10.1002/nau.22780. Epub 2015 Apr 24.

  PMID: 25914349 BACKGROUND

• Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003 May;20(6):327-36. doi: 10.1007/s00345-002-0301-4. Epub 2002 Nov 15.

  PMID: 12811491 BACKGROUND

• Tijnagel MJ, Scheepe JR, Blok BF. Real life persistence rate with antimuscarinic treatment in patients with idiopathic or neurogenic overactive bladder: a prospective cohort study with solifenacin. BMC Urol. 2017 Apr 13;17(1):30. doi: 10.1186/s12894-017-0216-4.

  PMID: 28403849 BACKGROUND

• Coyne KS, Thompson CL, Lai JS, Sexton CC. An overactive bladder symptom and health-related quality of life short-form: validation of the OAB-q SF. Neurourol Urodyn. 2015 Mar;34(3):255-63. doi: 10.1002/nau.22559. Epub 2014 Jan 13.

  PMID: 25783168 BACKGROUND

• Crowner BE, Torres-Russotto D, Carter AR, Racette BA. Systemic weakness after therapeutic injections of botulinum toxin a: a case series and review of the literature. Clin Neuropharmacol. 2010 Sep-Oct;33(5):243-7. doi: 10.1097/WNF.0b013e3181f5329e.

  PMID: 20852412 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder, Overactive

Interventions

onabotulinum toxin A; Botulinum Toxins, Type A

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

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Angela DiCarlo-Meacham, MD

  Walter Reed National Military Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angela DiCarlo-Meacham, MD

CONTACT

636-288-2955; angeladmmd@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 16, 2019
• Study Start: July 1, 2019
• Primary Completion: July 1, 2021
• Study Completion: December 31, 2021
• Last Updated: April 28, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)