Botox for Neurogenic Detrusor Overactivity and the Prevention of Autonomic Dysreflexia Following SCI

NCT02298660 | Completed Phase 4 DMC

• 1 other identifier: H12-02215
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the impact of 200 U intradetrusor injected OnabotulinumtoxinA (Botox®, Allergan, Inc.) (20 sites, trigone sparing) for neurogenic detrusor overactivity (NDO) and its role on reducing autonomic dysreflexia (AD) in those with chronic, traumatic spinal cord injury (SCI). In clinical practice, urinary bladder dysfunctions are commonly associated with episodes of AD. If AD is misdiagnosed or poorly managed, it may result in myocardial infarction, stroke, seizure, intracerebral hemorrhaging or even death. Reducing AD would dramatically improve the health and well-being of Canadians with SCI, and positively impact health care costs. There are an estimated 7,343 hospital re-admissions due to SCI-related conditions in Canada every year, with an estimated 5-year cost of $661 million. Reducing hospital re-admissions for secondary complications of SCI by only 10% over this time period could result in a costs savings of $66 million for Canada. Considering these statistics, the present study could be a first attempt to evaluate the economic impact of using Botox® to manage the urinary bladder following SCI. We will be able to examine its impact on episodes of AD and consequently calculate the cost saving for the Canadian health system. A significant number of individuals with SCI will require frequent emergency room visits due to episodes of uncontrolled AD that originate predominately from the urinary bladder. There is clinical evidence demonstrating that costs of bladder management following SCI will depend on the understanding of the volumes that the urinary bladder can safely hold. This is one of the positive outcomes that have been established in previous trials of Botox® therapy for the neurogenic bladder. Hypothesis: 200 U of intradetrusor injected Botox® (20 sites, trigone sparing) for neurogenic bladder detrusor hyperreflexia will decrease the severity of AD in individuals with SCI one month following treatment.

Conditions

Autonomic Dysreflexia

Keywords

Autonomic Dysreflexia; Spinal Cord Injury; OnabotulinumtoxinA; Neurogenic Detrusor Overactivity; Urodynamics; Cardiovascular; Quality of Life; Blood Pressure; 24 Hour Ambulatory Blood Pressure Monitoring

Outcome Measures

Primary Outcomes (1)

• Assess the efficacy of 200 U BOTOX® intradetrusor injections on amelioration of episodes of autonomic dysreflexia (AD) in individuals with chronic spinal cord injury during urodynamics (i.e. one month following treatment compared to baseline assessment)

  To assess the effect of intradetrusor injected BOTOX® on reducing AD (i.e. a smaller increase in systolic blood pressure during bladder filling compared to baseline) during urodynamics posttreatment vs pre-operative.

  One month

Secondary Outcomes (4)

• Reduction of spontaneous AD during daily living assessed with 24-hour ambulatory blood pressure monitoring (ABPM) following intradetrusor injections of BOTOX®.

  One month

• Cost analysis of BOTOX® treatment on AD following six months of treatment.

  One year

• The impact of BOTOX® to ameliorate AD-related QoL compared to baseline (i.e. improved AD HR-QoL posttreatment vs pre-operative).

  One month

• The impact of BOTOX® to ameliorate incontinence-related QoL compared to baseline (i.e. better I-QOL posttreatment vs pre-operative).

  One month

Study Arms (1)

BOTOX

EXPERIMENTAL

BOTOX® Total dose per patient: 200U Number of cycles:1 cycle Treatments will be conducted according to established protocol, 200 BOTOX® units with intradetrusor injections under cystoscopic guided injections into 20 sites, trigone sparing. One month later, urodynamics with continuous arterial blood pressure and electrocardiogram measurements will be repeated, as well as 24 hour ambulatory blood pressure monitoring. AD- HR QoL and I-QOL questionnaires will be administered to evaluate the effect of Botox on AD HR-QoL and bladder-related QoL.

Drug: BOTOX

Interventions

BOTOX DRUG

BOTOX® Total dose per patient: 200U Number of cycles:1 cycle 200 units of BOTOX® will be injected per procedure. BOTOX® will be diluted in 15mL saline to 20U/mL. BOTOX® injections will be performed with a normal 22 FF rigid cystoscopy or flexible 6Fr injection needle. BOTOX® will be injected into the detrusor muscle at 20 sites (10U per site), sparing the trigone. A local anaesthesia with instillation of 50 ml lidocaine 2% into the bladder will be done prior to the procedure to avoid autonomic dysreflexia.

Also known as: Botulinum toxin Type A, BTX-A,

BOTOX

Eligibility Criteria

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

You may qualify if:

• Inpatients or outpatients with SCI (AIS A-D)
• Male and female
• Age between 18 - 65
• Chronic, traumatic SCI (\> 1 year post injury)
• Affected by urinary incontinence
• We are expecting individuals with the following levels of injury:
• individuals with spinal segment thoracic (T) 6 and above (with history of episodes of AD) Presence of AD will be determined using a validated AD questionnaire.
• Good command and comprehension of English
• Capable of giving informed consent

You may not qualify if:

• Age older than 66 years
• Documented traumatic brain injury
• Acute co-morbidities
• Other diseases of the neural system
• Previous genitourinary disease or operation,
• Current urinary tract infection
• Multiple injury levels
• Previous history of systemic illness, such as cardiovascular diseases (as hypertension and cardiac infarction), cerebrovascular accident, diabetes, etc
• Poor command of English language
• Pregnancy

Sponsors & Collaborators

• Rick Hansen Institute: lead
• University of British Columbia: collaborator
• International Collaboration on Repair Discoveries: collaborator
• Vancouver Coastal Health: collaborator

Study Sites (1)

International Collaboration on Repair Discoveries (ICORD)

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (1)

• Krassioukov A, Biering-Sorensen F, Donovan W, Kennelly M, Kirshblum S, Krogh K, Alexander MS, Vogel L, Wecht J; Autonomic Standards Committee of the American Spinal Injury Association/International Spinal Cord Society. International standards to document remaining autonomic function after spinal cord injury. J Spinal Cord Med. 2012 Jul;35(4):201-10. doi: 10.1179/1079026812Z.00000000053.

  PMID: 22925746 BACKGROUND

Related Links

• International Collaboration on Repair Discoveries
• Rick Hansen Institute
• Krassioukov Lab Discovery + Clinical Research

MeSH Terms

Conditions

Autonomic Dysreflexia; Spinal Cord Injuries

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Autonomic Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Central Nervous System Diseases; Wounds and Injuries

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

• Andrei V. Krassioukov, M.D, PhD

  ICORD-Blusson, UBC, G.F. Strong Rehabilitation Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2012
• First Posted: November 24, 2014
• Study Start: April 1, 2013
• Primary Completion: October 17, 2017
• Study Completion: December 15, 2017
• Last Updated: December 26, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)