Prevention of Bladder Dysfunction in Acute Spinal Cord Injury

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Spinal Cord Injuries, Urinary Bladder, Overactive

Intervention / Treatment
-----------------
* Drug: Onabotulinumtoxin A
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>30 transurethral injections, each of 1 ml solution containing NaCl. | Drug: Placebo<br>* 30 transurethral injections, each of 1 ml solution containing NaCl.<br>* Other names: NaCl;|
| Active Comparator: Onabotulinumtoxin A<br>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<br>* 30 transurethral injections, each of 1 ml solution containing 300 U Onabotulinumtoxin A (Botox ®, Allergan) in 30 ml of NaCl 0.9 %.<br>* Other names: Botox ®, Allergan;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Spinal cord injury, Neurogenic overactive bladder, Onabotulinum toxin A, Prevention, Botulinum Toxins, Type A