Botulinum Toxin A Injections in Patients With Fowler's Syndrome

NCT02428881 | Completed Phase 2 DMC

• 1 other identifier: 08/0216
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

Hypothesis / aims of study Urinary retention is uncommon in young women, and one cause is a primary disorder of urethral sphincter relaxation, characterised by an elevated urethral pressure profile and specific findings in the urethral sphincter EMG (Fowler's Syndrome). Women may present with symptoms of obstructed voiding or complete urinary retention. Clean intermittent self-catheterisation is often painful to perform and currently, the only treatment to show benefit is sacral neuromodulation. This aim of this pilot study is to assess the efficacy of urethral sphincter injections of botulinum toxin, defined as improvement of flow rates by more than 50%, improvement in residual volume and scores on the IPSS questionnaire, and safety, in women with Fowler's Syndrome. Study design, materials and methods In this open label pilot institutional review board approved study, ten women with a primary disorder of urethral sphincter relaxation (elevated urethral pressure profile (UPP), sphincter volume and abnormal EMG) presenting with obstructed voiding (n=5) or in complete urinary retention (n=5) are recruited from a single tertiary referral centre. Baseline symptoms are being assessed using the IPSS questionnaire, and urinary flow and post-void residual volume were measured. After 2% lidocaine injection, 100U of onabotulinumtoxintypeA is being injected into the striated urethral sphincter, divided on either side, under EMG guidance. Patients are being reviewed at weeks 1, 4 and 10 post-treatment and symptoms are reassessed using the IPSS questionnaire, and urinary flow and post-void residual volume are being measured. The UPP is being repeated at week 4.

Conditions

Urinary Retention; Fowler's Syndrome

Keywords

onabotulinumtoxin A

Outcome Measures

Primary Outcomes (2)

• Improvement in urinary flow rates as assessed by uroflowmetry by more than 50%

  Improvement in urinary flow rates (as assessed by uroflowmetry and measured in mL/sec) by more than 50% after botulinum toxin compared to baseline in women with obstructed voiding

  10 weeks

• Restoration of voiding for women in complete urinary retention

  Restoration of voiding (either yes or no) after botulinum toxin for women in complete urinary retention

  10 weeks

Secondary Outcomes (2)

• Improvement of post void residual urine compared to baseline

  10 weeks

• Improvement in lower urinary tract symptoms as assessed by an improvement in scores on the IPSS questionnaire

  10 weeks

Study Arms (2)

Complete retention- onabotulinumtoxinA

EXPERIMENTAL

Women in complete urinary retention receiving onabotulinumtoxinA

Drug: onabotulinumtoxinA

Obstructed voiding- onabotulinumtoxinA

EXPERIMENTAL

Women with obstructed voiding receiving onabotulinumtoxinA

Drug: onabotulinumtoxinA

Interventions

onabotulinumtoxinA DRUG

Patients received 100U onabotulinumtoxinA injection into the external urethral sphincter

Also known as: Botox

Complete retention- onabotulinumtoxinA; Obstructed voiding- onabotulinumtoxinA

Eligibility Criteria

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

You may qualify if:

• Women 18 years old or over with diagnosed Fowler's syndrome and abnormal sphincter function i.e. raised UPP {MUCP\>(92 - patient age in years) cmH2O} (Edwards and Malvern 1974), increased sphincter volume(if measured) (greater than 1.8 cm3) and if voiding, evidence of obstructed outflow. (Sphincter EMG will be recorded at the time of injection.)
• Willing to give written informed consent
• Willing to attend the necessary follow up visits
• On effective contraception if sexually active - oral contraceptive pill (\>3 months use), condoms, intrauterine contraceptive device, depot injection

You may not qualify if:

• Previous urethral surgery (other than urethral dilatation)
• Neurological disease
• Pregnant or lactating women and those planning pregnancy
• On drugs that might interfere with neuromuscular transmission (e.g. aminoglycosides)
• Pain thought to originate from the urinary tract
• Unsuitable past medical history e.g. frequent epilepsy, uncontrolled hypertension, severe coronary artery disease.
• Symptomatic Urinary Tract Infection with a positive urine culture
• Participation in a clinical trial involving an investigational product in the last 3 months
• Patients who are unable to understand or speak English, as this is a pilot study involving very few patients.

Sponsors & Collaborators

• University College, London: lead

Related Publications (3)

• Dykstra DD, Sidi AA, Scott AB, Pagel JM, Goldish GD. Effects of botulinum A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol. 1988 May;139(5):919-22. doi: 10.1016/s0022-5347(17)42717-0.

  PMID: 3361663 BACKGROUND

• Dasgupta R, Wiseman OJ, Kitchen N, Fowler CJ. Long-term results of sacral neuromodulation for women with urinary retention. BJU Int. 2004 Aug;94(3):335-7. doi: 10.1111/j.1464-410X.2004.04979.x.

  PMID: 15291863 RESULT

• Swinn MJ, Wiseman OJ, Lowe E, Fowler CJ. The cause and natural history of isolated urinary retention in young women. J Urol. 2002 Jan;167(1):151-6.

  PMID: 11743295 RESULT

MeSH Terms

Conditions

Urinary Retention; Fowler Christmas Chapple syndrome

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2015
• First Posted: April 29, 2015
• Study Start: November 1, 2009
• Primary Completion: July 1, 2012
• Last Updated: April 29, 2015

Record last verified: 2015-04