Early BOTOX After Spinal Cord Injury

NCT06793683 | Enrolling By Invitation Early Phase 1

• 1 other identifier: STUDY00018758
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injuries

Keywords

SCI; Neurogenic Bladder; Chemodenervation with BoNT-A; Botox; Autonomic Dysreflexia

Outcome Measures

Primary Outcomes (2)

• Feasibility of Enrollment goals

  Outcomes of this pilot trial will provide human data on the feasibility of recruiting 10 participants into a randomized study of early chemodenervation. The enrollment goal is 10 participants who will complete the 12-month study protocol. If ≥ 8 participants complete the protocol, it will be considered feasible. If ≤ 5 participants complete the protocol, it will be considered unfeasible. If 6-7 participants complete the study, it will be considered indeterminate.

  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

  Patients will be monitored for adverse events as a result of the procedures. * Evidence of Urinary Tract Infections * Hematuria * Anesthesia Complications Any adverse events (AE) will be graded 1 through 5, with unique clinical descriptions of severity for each AE, based upon the AE guidelines as published in the CAE v4.0

  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 (2)

• Variance of measurements for functional data

  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

  Variances of all measurements and data will be analyzed at the conclusion of the study (expected in 2028).

Study Arms (2)

Bladder Chemodenervation (Botox) Injection Procedure

ACTIVE COMPARATOR

BoNT-A (Botox) 200 U, will be injected into the detrusor (bladder wall muscle).

Drug: Bladder chemodenervation (Botox)

Bladder Sham (saline) Injection Procedure

SHAM COMPARATOR

Saline will be injected into the detrusor (bladder wall muscle).

Procedure: Bladder Sham (Saline) Injection Procedure

Interventions

Bladder chemodenervation (Botox) DRUG

BoNT-A (Botox) 200 U will be injected into the detrusor (bladder wall muscle).

Bladder Chemodenervation (Botox) Injection Procedure

Bladder Sham (Saline) Injection Procedure PROCEDURE

20mL placebo (saline only), will be injected into the detrusor (bladder wall muscle).

Bladder Sham (saline) Injection Procedure

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Publications (9)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 36356027 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries; Urinary Bladder, Neurogenic; Autonomic Dysreflexia

Interventions

Botulinum Toxins, Type A; Sodium Chloride; Injections

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Neurologic Manifestations; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Autonomic Nervous System Diseases

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; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Claire C Yang, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be blinded during the study.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor: Department of Urology

Model Details: 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).

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: January 27, 2025
• Study Start: July 27, 2024
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: January 27, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)