Early BOTOX After Spinal Cord Injury

Official title

Early Detrusor Chemodenervation to Preserve Bladder Compliance and Longevity After Spinal Cord Injury

Overview

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.

Interventions

• Drug Bladder chemodenervation (Botox)
  BoNT-A (Botox) 200 U will be injected into the detrusor (bladder wall muscle).
• Procedure Bladder Sham (Saline) Injection Procedure
  20mL placebo (saline only), will be injected into the detrusor (bladder wall muscle).

Primary outcome measures

• Feasibility of Enrollment goals [Time frame: Each participant will be evaluated for a period of up to 12 months after the time of enrollment.]
• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Time frame: 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 outcome measures (2)

• Variance of measurements for functional data [Time frame: Variances of all measurements and data, for each subject, will be analyzed at the conclusion of their study participation, 12 months post enrollment.]
• Variance of measurements for histological data [Time frame: Variances of all measurements and data will be analyzed at the conclusion of the study (expected in 2028).]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

United States · 1 center

• Harborview Medical Center — Seattle

Publications

• 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. PMID 16517054
• 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. PMID 22503020
• 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. PMID 16317536
• 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. PMID 9776015
• 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. PMID 29352989
• 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. PMID 37096828
• 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. PMID 24518764
• 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. PMID 24708598

Identifiers

NCT: NCT06793683 · STUDY00018758

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗