Botulinum Toxin a Vs Anticholinergic Treatment of Neurogenic Overactive Bladder in Patients with Multiple Sclerosis

NCT04819360 | Terminated Phase 4

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

Brief Summary

Botulinum toxin type A injections into the detrusor at a dose of 200 units (U) of BOTOX® are a recognized second-line treatment for the treatment of adult neurogenic lower urinary tract disorders. Anticholinergics are established as the usual first-line treatment for neurogenic detrusor hyperactivity, but are oft not sufficiently effective and have significant side effects. In patients with multiple sclerosis (MS) suffering from overactive bladder, the 200 U dose of BOTOX® is very effective but induces a risk of urinary retention in 30% of patients requiring the temporary use of self-catheterization1. At 100 U, a recent study shows the efficacy and very good tolerance of botulinum toxin A in terms of probing risk in MS patients with overactive bladder and failure of anticholinergics. Furthermore, the efficacy of anticholinergics in MS has been little studied and is also disputed. The investigators plan to test the therapeutic alternative as the first line of treatment in two groups of randomized MS patients from a homogeneous population suffering from overactive bladder:

• a group testing the effectiveness of low doses of botulinum toxin type A (100 U, BOTOX®),
• the other group receiving the standard anticholinergic treatment (solifenacin succinate, Vesicare®). During this pilot study, the efficacy and side effects profile of each treatment will be analyzed in order to determine the amplitudes of effect and the safety profiles in this population and in order to establish the statistical hypotheses for a subsequent randomized multicenter study. The aim of this study will be to establish the benefit of botulinum toxin at a dose of 100 U as a first-line treatment instead of anticholinergics

Conditions

Urinary Bladder, Neurogenic; Multiple Sclerosis

Keywords

Botulinum toxin; Neurogenic bladder; Multiple sclerosis; Anticholinergic drugs

Outcome Measures

Primary Outcomes (1)

• Magnitude of effect - Number of micturitions per 24h

  The difference in mean values of \[the number of micturitions / 24 h for the last 3 days\] at T0 (inclusion) and T6W (6 weeks after start of the treatment).

  6 weeks

Secondary Outcomes (9)

• Other parameters of effects - Number of urgent urinations per 24h

  2, 6 and 12 weeks after treatment start

• Other parameters of effects - Number of urgency urinary incontinence episodes per 24h

  2, 6 and 12 weeks after treatment start

• Other parameters of effects - Number of nocturnal micturition episodes per 24h

  2, 6 and 12 weeks after treatment start

• Other parameters of effects - Number of 100% dry patients

  6 and 12 weeks after treatment start

• Other parameters of effects - Urodynamic parameter : cystomanometric capacity

  6 weeks after treatment start

Other Outcomes (7)

• Patients reported outcomes - Patients' satisfaction

  2, 6 and 12 weeks

• Patients reported outcomes - Patients' specific quality of life

  2, 6 and 12 weeks

• Patients reported outcomes - Subjective improvement

  2, 6 and 12 weeks

Study Arms (2)

Vesicare

ACTIVE COMPARATOR

Group 1: will be treated with an anticholinergic (Vesicare® 10 mg per day for 12 weeks)

Drug: VESIcare 10Mg Tablet

Botox

ACTIVE COMPARATOR

Group 2: will receive an intra-detrusor injection of a low dose of botulinum toxin type A (100 U of BOTOX®).

Drug: Botox 100 UNT Injection

Interventions

VESIcare 10Mg Tablet DRUG

Vesicare® 10 mg per day for 12 weeks Vesicare 10mg 12 weeks

Also known as: Vesicare

Vesicare

Botox 100 UNT Injection DRUG

1 injection of Botox® 100 UNT

Also known as: Botox

Botox

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with multiple sclerosis (MS) with neurogenic detrusor overactivity proven by urodynamics
• Stable MS with an Expanded Disability Severity Score (EDSS) less than or equal to 6.5
• Voluntary micturitions
• Number of micturitions \> 8 per day, with or without episodes of urgency and urgency incontinence
• Signed informed consent form

You may not qualify if:

• Pregnancy, breastfeeding
• Patients requiring self-catheterizations
• Patients unable or unwilling to learn self-catheterisation
• Recent (\<12 weeks) or current treatment with botulinum toxin for any non-urological indication
• Recent (≤ 8 weeks) or current treatment with anticholinergic drugs
• Patients with a positive history or evidence of pelvic / urological abnormality (interstitial cystitis, bladder lithiasis in the 6 months preceding the screening, or any other condition / operation affecting the bladder or prostate)
• Any contraindication to Vesicare®:
• Hypersensitivity to the active ingredient or to one of the excipients
• Urinary retention
• Untreated narrow-angle glaucoma
• Severe gastrointestinal illness (e.g. toxic megacolon)
• Myasthenia gravis
• Severe hepatic failure
• Hemodialysis
• Severe renal failure, or liver function disturbances of moderate severity with concomitant treatment with a strong inhibitor of the CYP3A4 isoenzyme, including patients at risk for these diseases.

Sponsors & Collaborators

• Brigitte Schürch: lead
• Centre Hospitalier Universitaire Vaudois: collaborator

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

Related Publications (1)

• Chermansky C, Schurch B, Rahnama'i MS, Averbeck MA, Malde S, Mancini V, Valentini F, Sahai A. How can we better manage drug-resistant OAB/DO? ICI-RS 2018. Neurourol Urodyn. 2019 Dec;38 Suppl 5:S46-S55. doi: 10.1002/nau.24055.

  PMID: 31821628 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder, Neurogenic; Multiple Sclerosis

Interventions

Solifenacin Succinate; Tablets; Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; 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; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dosage Forms; Pharmaceutical Preparations; 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

• Brigitte Schürch, Prof.

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 13, 2020
• First Posted: March 26, 2021
• Study Start: June 1, 2021
• Primary Completion: March 9, 2022
• Study Completion: April 21, 2024
• Last Updated: September 27, 2024

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)