Neurogenic Detrusor Overactivity Following Spinal Cord Injury or Multiple Sclerosis

A Phase IIa, Multicentre, Double Blind, Single Dose, Parallel Group, Placebo Controlled, Clinical Pilot Study to Assess the Efficacy and Safety of a Single Dose, Intra-Detrusor Injections of 750 Units of Dysport® in Subjects Suffering From Neurogenic Detrusor Overactivity Following Spinal Cord Injury or Multiple Sclerosis.

The purpose of this study is to determine the efficacy and safety of a single dose of 750 U of Dysport compared to placebo for the improvement in the daily incontinence episode frequency for each administration mode in subjects suffering from neurogenic detrusor overactivity following spinal cord injury or multiple sclerosis.

Study Overview

• Status: Completed
• Conditions: Detrusor Muscle Hyperactivity
• Intervention / Treatment: Biological: Botulinum toxin type A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Praha, Czechia
    • Faculty Hospital Motol
  • Praha, Czechia
    • THOMAYER Faculty Hospital
• France
  • Garches, France
    • Hopital Raymond Poincare
  • Lille, France
    • Hopital HURIET
  • Lyon, France
    • Hôpital Lyon Sud -Hospices Civils de Lyon
  • Marseille, France
    • Hôpital de la Conception
  • Nantes, France
    • Chu Hotel Dieu
  • Paris, France
    • Hopital Tenon
  • Paris, France
    • Groupe Hospitalier La Pitié Salpêtrière
  • Ploemeur, France
    • CMRRF Kerpape
  • Rouen, France
    • CHU ROUEN - Hôpital Charles Nicolle
  • Strasbourg, France
    • Nouvel Hôpital Civil de Strasbourg
  • Toulouse, France
    • CHU Toulouse - Hôpital Rangueil
• Germany
  • Kiel, Germany
    • Universitätsklinik Kiel
  • Neunkirchen, Germany
    • Städtisches Klinikum Neunkirchen
• Italy
  • Firenze, Italy
    • Ospedale Careggi
• Poland
  • Warszawa, Poland
    • NZOZ Centrum Medyczne Mazovia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject, family member or care giver was willing and able to perform clean intermittent catheterisation (CIC) for the duration of the study
• Inadequate response or refractory to anticholinergic medication
• Botulinum Toxin naive for intradetrusor injections and with no previous treatment with Botulinum Toxin of any type, within 3 months prior to study entry for any other condition
• Have a minimum of 2 incontinences per day calculated as the average daily incontinence episode frequency (IEF) over the 3 days preceding the baseline visit

Exclusion Criteria:

• Significant Baseline renal and/or urinary tract pathology
• Previous treatment with any endovesical pharmacology agent including detrusor Botulinum Toxin injection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dysport 750 U (15 injection sites)	Biological: Botulinum toxin type A; 750 U intra detrusor injection on Day 1 (single dose); Other Names: AbobotulinumtoxinA (Dysport®)
Placebo Comparator: Placebo (15 injection sites)	Drug: Placebo; Intra detrusor injection on Day 1 (single dose)
Experimental: Dysport 750 U (30 injection sites)	Biological: Botulinum toxin type A; 750 U intra detrusor injection on Day 1 (single dose); Other Names: AbobotulinumtoxinA (Dysport®)
Placebo Comparator: Placebo (30 injection sites)	Drug: Placebo; Intra detrusor injection on Day 1 (single dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Daily Incontinence Episode Frequency (IEF)	Baseline and Day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urodynamics: Maximum Cystometric Capacity	Maximum Cystometric Capacity is an urodynamic parameter that indicates the volume at which a patient feels he (she) can no longer delay release of urine from the urinary bladder. Baseline urodynamics exams done at screening visit.	Baseline, Days 14, 42 and 84
Urodynamics:Maximum Detrusor Pressure	Maximum Detrusor Pressure is an urodynamic parameter that is the maximum value of the pressure within the bladder which is measured during the filling phase of the urodynamic exam. Baseline urodynamics exams done at screening visit.	Baseline, Days 14, 42 and 84
Physician's Global Assessment Score of Treatment Response	The subject's treatment response was assessed by the physician and graded as 'markedly worse', 'much worse', 'worse', 'slightly worse', 'no change', 'slightly improved', 'improved', 'much improved', or 'markedly improved'.	Day 14
Physician's Global Assessment Score of Treatment Response	The subject's treatment response was assessed by the physician and graded as 'markedly worse', 'much worse', 'worse', 'slightly worse', 'no change', 'slightly improved', 'improved', 'much improved', or 'markedly improved'.	Day 42
Physician's Global Assessment Score of Treatment Response	The subject's treatment response was assessed by the physician and graded as 'markedly worse', 'much worse', 'worse', 'slightly worse', 'no change', 'slightly improved', 'improved', 'much improved', or 'markedly improved'.	Day 84
Quality of Life (QoL) Total Summary Score	Mean Change from Baseline in Short Form (SF)-Qualiveen Questionnaire Calculated Total Score. The SF-Qualiveen questionnaire is a specific health related QoL questionnaire validated for urinary disorders in subjects with neurological conditions containing 8 items looking at four scales: limitations (2 items); constraints (2 items); fears (2 items) and feelings (2 items). The 8 items each having a 5-point Likert-type scale ranging from 0="Not at all" to 4="Extremely" for the first 6 items, from 0="Never" to 4="Always" for item 7 and from 0="Always" to 4="Never" for item 8. The score per scale has been calculated as the mean of the two items. In case of one missing item among the 2 items for a given scale, the score has not been calculated. Total score has been calculated as the mean of all the items completed among the 8 items. Lower scores indicate a better QoL (i.e. no limitations, fears, constraints, or negative feelings) and higher scores indicate poorer QoL.	Baseline, 14, 42 and 84
Pain Visual Analogue Scale (VAS) Score: Before Treatment Injection	Pain assessment using the VAS. The VAS is a 100-mm (10-cm) scoring scale. Score range on VAS is from 0 to 100 where zero [0] indicates no pain and 100 indicates worst possible pain.	Baseline
Pain Visual Analogue Scale (VAS) Score: During Treatment Injection Procedure	Pain assessment using the VAS. The VAS is a 100-mm (10-cm) scoring scale. Score range on VAS is from 0 to 100 where zero [0] indicates no pain and 100 indicates worst possible pain.	Baseline

Collaborators and Investigators

• Sponsor: Ipsen

Publications and helpful links

General Publications

• Denys P, Del Popolo G, Amarenco G, Karsenty G, Le Berre P, Padrazzi B, Picaut P; Dysport Study Group. Efficacy and safety of two administration modes of an intra-detrusor injection of 750 units dysport(R) (abobotulinumtoxinA) in patients suffering from refractory neurogenic detrusor overactivity (NDO): A randomised placebo-controlled phase IIa study. Neurourol Urodyn. 2017 Feb;36(2):457-462. doi: 10.1002/nau.22954. Epub 2016 Jan 12.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: May 17, 2011
• First Submitted That Met QC Criteria: May 20, 2011
• First Posted (Estimate): May 23, 2011

Study Record Updates

• Last Update Posted (Actual): September 27, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Detrusor Muscle Overactivity
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Multiple Sclerosis; 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; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: Y-52-52120-155; 2010-023210-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).