Prevention of Bladder Dysfunction in Acute Spinal Cord Injury (BOT-SCI)

Prevention of Bladder Dysfunction in Acute Spinal Cord Injury. A Double-blind, Randomized, Placebo-controlled Study to Explore the Effect of Early Treatment With Onabotulinumtoxin A on Development of Detrusor Overactivity

This study is a double blind, randomized, placebo controlled trial to explore the effect of early treatment with Onabotulinumtoxin A in patients with acute complete motor spinal cord injury (SCI) on the development of neurogenic detrusor overactivity (NDO). A total of 20 patients will be randomized to intra-detrusor injection of 300 U Onabotulinumtoxin A in 30 ml NaCl 0.9 % or placebo with 30 ml NaCl 0.9 %. Bladder biopsies will be obtained in the same procedure. The treatment will be repeated after three months. All included patients will be evaluated with urodynamic examinations. Follow-up is 12 months after the first treatment. The primary endpoint of the study is development of NDO.

Study Overview

• Status: Completed
• Conditions: Urinary Bladder, Overactive; Spinal Cord Injuries
• Intervention / Treatment: Drug: Placebo; Drug: Onabotulinumtoxin A

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Nesoddtangen, Norway, 1450
    • Sunnaas Hospital
  • Oslo, Norway, 0027
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with documented acute, motor complete C6 to Th11 spinal cord injury
• Patients can be included in the study less than four weeks after injury
• Male or female, aged 18 to 80 years old
• Patient weight > 40 kg
• Patient is able and willing to sign informed consent
• Patient is able to complete all study requirements

Exclusion Criteria:

• Neurogenic detrusor overactivity with contractions greater than 40 cm H2O at first visit
• History or evidence of previous urological abnormalities, disease or surgery, except bladder dysfunction after spinal cord injury
• History of haematuria or ongoing haematuria, if the hematuria is determined to be a pathologic condition or is uninvestigated
• Pregnancy or females of childbearing potential unwilling to use a reliable form of contraception
• Breastfeeding
• Known allergy to Onabotulinumtoxin A
• Grave psychiatric disorder
• Use of anti-platelet or anti-coagulant other than low molecular weight heparin (LMWH) or acetylsalicylic acid
• Haemophilia or other clotting disorders that cause bleeding diathesis
• Treatment with antimuscarinic medication within 3 months of randomization
• Treatment with botulinum toxin of any serotype within 3 months of randomization
• Patient has been immunized for any botulinum toxin serotype
• Patient has any medical condition that may put the patient at increased risk with exposure to botulinum toxin including diagnosed myasthenia gravis, Eaton-Lambert syndrome or amyotrophic lateral sclerosis
• Patient has any condition or situation, which, in the investigator's opinion, puts the patient at significant risk, could confound the study results, or may interfere significantly with the patient's participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; 30 transurethral injections, each of 1 ml solution containing NaCl.	Drug: Placebo; 30 transurethral injections, each of 1 ml solution containing NaCl.; Other Names: NaCl
ACTIVE_COMPARATOR: Onabotulinumtoxin A; 30 transurethral injections, each of 1 ml solution containing 300 U Onabotulinumtoxin A (Botox ®, "Allergan") in 30 ml of NaCl 0.9 %.	Drug: Onabotulinumtoxin A; 30 transurethral injections, each of 1 ml solution containing 300 U Onabotulinumtoxin A (Botox ®, "Allergan") in 30 ml of NaCl 0.9 %.; Other Names: Botox ®, "Allergan"

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Presence of neurogenic detrusor overactivity during cystometry, defined as contractions with amplitudes above 40 cm H2O.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urodynamic parameters	Maximal detrusor pressure (cmH2O), maximal bladder capacity (ml), compliance (ΔcmH2O/Δml), and occurrence of DSD.	12 months
Quality of life (QOL) in the treated group compared to the placebo group 12 months after first treatment.		12 months
Occurrence of complications.		12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detrusor pathophysiology	Differences in levels of transmitters and receptors relevant to development of bladder dysfunction, measured in urine samples and bladder biopsies, to gain knowledge of the pathophysiology behind neurogenic detrusor overactivity.	12 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Sunnaas Rehabilitation Hospital
• Investigators: Principal Investigator: Lars Frich, MD, PhD, University of Oslo; Principal Investigator: Ole Jacob Nilsen, MD, University of Oslo; Principal Investigator: Thomas Glott, MD, Sunnaas Rehabilitation Hospital, Norway

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (ACTUAL): December 20, 2020
• Study Completion (ACTUAL): December 20, 2020

Study Registration Dates

• First Submitted: September 26, 2012
• First Submitted That Met QC Criteria: September 28, 2012
• First Posted (ESTIMATE): October 2, 2012

Study Record Updates

• Last Update Posted (ACTUAL): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Prevention; Spinal cord injury; Botulinum Toxins, Type A; Onabotulinum toxin A; Neurogenic overactive bladder
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Trauma, Nervous System; Spinal Cord Diseases; Urinary Bladder, Overactive; Wounds and Injuries; Spinal Cord Injuries; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 2012/1151

Plan for Individual participant data (IPD)

Study Data/Documents

1. Statistical Analysis Plan
   Information comments: Statistical analysis plan version 1.0.