Clinical trial NCT06793683: Early BOTOX After Spinal Cord Injury
Official title: Early Detrusor Chemodenervation to Preserve Bladder Compliance and Longevity After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: EARLY_PHASE1
Conditions: Spinal Cord Injuries
Keywords: SCI
Neurogenic Bladder
Chemodenervation with BoNT-A
Botox
Autonomic Dysreflexia
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2025-01-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators hope to recruit 10 participants randomly assigned to 7 cases (those that will receive Botox bladder injections) and 3 controls (those that will receive placebo bladder injections).
Primary purpose: PREVENTION

Brief summary: The investigators would like to improve our understanding of how early intervention with the use of bladder chemodenervation can preserve bladder function in those with a new SCI. Although detrimental cystometric and tissue changes are known to occur, often within 3 months after SCI, the investigators seek to document the time course of these changes and the range of severity of those changes in both those participants that receive prophylactic treatment and those who do not.


Eligibility criteria: Inclusion Criteria:

* Male or female 18-65 years of age at time of SCI.
* English speaking
* Recent SCI (within 20 weeks of injury).
* Documentation of a spinal cord injury at T6 or higher, American Spinal Injury Association Impairment Scale (AIS) level A or B as designated on initial (72 hour) AIS exam.
* Ability for subject to comply with the requirements of the study.
* Written informed consent obtained from subject.

Exclusion Criteria:

* Inability to return to research site (Harborview Medical Center) for follow-up studies after initial hospitalization.
* Acute (as part of concurrent hospitalization) or history of bladder surgery (urethral or prostate surgery acceptable) or injury.
* Inability to provide informed consent.
* Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
* Incarcerated in a detention facility or in police custody.
* Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
* Active medical problems precluding the safe conduct of urodynamics, bladder chemodenervation, bladder biopsy (e.g., evidence of active bladder infection, ruled out by urine culture prior to procedures)
* Known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation
* Cardiovascular instability

Primary outcomes:
measure: Feasibility of Enrollment goals
timeFrame: Each participant will be evaluated for a period of up to 12 months after the time of enrollment.
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: For each participant any AE's will be documented, at time of AE, beginning at study enrollment and throughout each participants 12 month enrollment period.
Secondary outcomes:
measure: Variance of measurements for functional data
timeFrame: Variances of all measurements and data, for each subject, will be analyzed at the conclusion of their study participation, 12 months post enrollment.
measure: Variance of measurements for histological data
timeFrame: Variances of all measurements and data will be analyzed at the conclusion of the study (expected in 2028).
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
Study officials:
affiliation: University of Washington
name: Claire C Yang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Comperat E, Reitz A, Delcourt A, Capron F, Denys P, Chartier-Kastler E. Histologic features in the urinary bladder wall affected from neurogenic overactivity--a comparison of inflammation, oedema and fibrosis with and without injection of botulinum toxin type A. Eur Urol. 2006 Nov;50(5):1058-64. doi: 10.1016/j.eururo.2006.01.025. Epub 2006 Feb 6.
citation: Ginsberg D, Gousse A, Keppenne V, Sievert KD, Thompson C, Lam W, Brin MF, Jenkins B, Haag-Molkenteller C. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012 Jun;187(6):2131-9. doi: 10.1016/j.juro.2012.01.125. Epub 2012 Apr 12.
citation: Ku JH, Choi WJ, Lee KY, Jung TY, Lee JK, Park WH, Shim HB. Complications of the upper urinary tract in patients with spinal cord injury: a long-term follow-up study. Urol Res. 2005 Dec;33(6):435-9. doi: 10.1007/s00240-005-0504-4. Epub 2005 Nov 30.
citation: Janzen J, Vuong PN, Bersch U, Michel D, Zaech GA. Bladder tissue biopsies in spinal cord injured patients: histopathologic aspects of 61 cases. Neurourol Urodyn. 1998;17(5):525-30. doi: 10.1002/(sici)1520-6777(1998)17:53.0.co;2-f.
citation: Bywater M, Tornic J, Mehnert U, Kessler TM. Detrusor Acontractility after Acute Spinal Cord Injury-Myth or Reality? J Urol. 2018 Jun;199(6):1565-1570. doi: 10.1016/j.juro.2018.01.046. Epub 2018 Jan 17.
citation: Rosier PFWM, Valdevenito JP, Smith P, Sinha S, Speich J, Gammie A; Members of the ICS Working Group PFS23. ICS-SUFU standard: Theory, terms, and recommendations for pressure-flow studies performance, analysis, and reporting. Part 1: Background theory and practice. Neurourol Urodyn. 2023 Nov;42(8):1590-1602. doi: 10.1002/nau.25192. Epub 2023 Apr 25.
citation: Welk B, Morrow S, Madarasz W, Baverstock R, Macnab J, Sequeira K. The validity and reliability of the neurogenic bladder symptom score. J Urol. 2014 Aug;192(2):452-7. doi: 10.1016/j.juro.2014.01.027. Epub 2014 Feb 8.
citation: Tang DH, Colayco D, Piercy J, Patel V, Globe D, Chancellor MB. Impact of urinary incontinence on health-related quality of life, daily activities, and healthcare resource utilization in patients with neurogenic detrusor overactivity. BMC Neurol. 2014 Apr 4;14:74. doi: 10.1186/1471-2377-14-74.
citation: Bushnell JY, Cates LN, Hyde JE, Hofstetter CP, Yang CC, Khaing ZZ. Early Detrusor Application of Botulinum Toxin A Results in Reduced Bladder Hypertrophy and Fibrosis after Spinal Cord Injury in a Rodent Model. Toxins (Basel). 2022 Nov 10;14(11):777. doi: 10.3390/toxins14110777.