Preventing UTIs in Chronic Neurogenic Bladder Dysfunction (Mix Methods)
Preventing UTIs in Chronic Neurogenic Bladder Dysfunction (Mix Methods)
Due to the damage caused to the spinal cord, patients with spinal cord injury, cauda equina
 syndrome, multiple sclerosis and transverse myelitis may encounter loss of bladder function,
 which in turn can lead to a debilitating and costly complication: Urinary Tract Infections
 (UTIs). Given that these patients with loss of bladder function do not normally feel symptoms
 like pain - as would be the case in otherwise healthy persons - there is no clear agreement
 among experts on which signs and symptoms are indicative of a UTI. Although strong evidence
 is lacking, antibiotics have been widely used for prevention of recurrent UTIs in patients
 with loss of bladder function. However, this approach is now being questioned as antibiotic
 resistance has become a world-wide health concern. Policy makers recently stressed the
 importance of research into alternative preventative treatments. The use of immunotherapy is
 one such an alternative approach, which works by stimulating the body's immune system. One of
 these immunotherapy is a Uro-Vaxom® oral capsule which consists of inactivated traces of the
 bacteria that normally cause at least 83% of UTIs in patients with loss of bladder function.
 Previous studies show that Uro-Vaxom® resulted in a significant reduction of UTIs in
 otherwise healthy patients, as well as being safe to use. Before investigating the effects of
 this promising new immunotherapy, this proposed study aims to clarify two crucial issues.
 First, after reviewing the literature and appraising patients', carers' and healthcare
 professionals' experiences, the aim is to reach an agreement on how to measure a symptomatic
 UTI in patients with loss of bladder function that results from a spinal cord lesion. Second,
 using Uro-Vaxom® Investigators aim to conduct a smallscale, placebo-controlled trial with 48
 participants to investigate the feasibility of carrying out a larger trial on prevention of
 symptomatic UTI in such patients.
Each year in the UK 1,200 people sustain a spinal cord injury, 600 people will be diagnosed
 with cauda equina syndrome, 6,000 with multiple sclerosis and 300 with transverse myelitis.
 These four patient groups all suffer from neurological disorders of the spinal cord,
 resulting in loss of normal bladder function known as neurogenic bladder dysfunction. This in
 turn can lead to urinary tract infections (UTIs). UTIs are a commonly recurring and
 debilitating complication, with spinal patients experiencing 2.5 episodes per patient per
 year on average. This not only results in 16% of hospital readmissions and costs of care of
 up to £125 million spent by the NHS on treating UTIs every year, but also has a dramatic
 impact on patients' quality of life.

 A recent NICE guideline highlighted the methodological difficulties of research into the
 prevention of UTIs in patients with neurogenic bladder dysfunction. Given that this group of
 patients normally do not feel symptoms like 'pain' and 'a frequent urge to urinate', it can
 be difficult to distinguish between bladder colonisation (asymptomatic bacteriuria) and true
 infection (a symptomatic UTI). To date, there is no clear agreement among experts on which
 signs and symptoms are indicative of a symptomatic UTI. Although strong evidence is lacking,
 antibiotics have been widely used for the prevention of recurrent UTIs in patients with
 neurogenic bladder dysfunction. However, this approach is now being called into question as
 antibiotic resistance has become a world-wide health concern.

 In the recently published 'UK Five Year Antimicrobial Resistance Strategy', policy makers
 stressed the importance of research into alternative preventative treatments. Immunotherapy
 potentially offers such a (cost-) effective alternative to antibiotic therapy for UTI
 management. At least 83% of community-acquired complicated UTIs are caused by Escherichia
 coli (E. coli). Uro-Vaxom® (OM-Pharma, Switzerland) is an orally administered, bacterial
 vaccine which consists of a 6mg lyophilised (heat-inactivated) mix of E. coli membrane
 glycoproteins.

 Previous studies showed that Uro-Vaxom® resulted in a significant reduction of UTIs in
 otherwise healthy women with recurrent cystitis, as well as being safe to use.

 Before investigating the effects of this promising new vaccine in patients with neurogenic
 bladder dysfunction, two crucial issues will need to be clarified. First, consensus must be
 reached on how to measure a symptomatic UTI in this group of patients. Second, the
 feasibility of carrying out a larger, definitive randomised controlled trial on the
 prevention of symptomatic UTI in patients with neurogenic bladder dysfunction must be
 established. The central aim of the proposed mixed method study is to clarify these two key
 methodological and feasibility issues.

 In the first stage of this study is to carry out qualitative interviews to explore patient
 experiences and views of symptoms and signs associated with a UTI. These results, combined
 with findings from a literature review, will enable the design of a quantitative patient
 survey which will be distributed by four service user organisations to people with neurogenic
 bladder dysfunction. Finally, taking the results from all preceding stages, a final
 definition, or algorithm, will be discussed before and during a consensus meeting.

 In the second stage of this study, a small-scale parallel, double-blinded, randomised,
 placebo-controlled, multicentre trial will be conducted to investigate the feasibility of
 carrying out a larger well-powered study on the prevention of symptomatic UTI in patients
 with neurogenic bladder dysfunction. Forty-eight patients will be randomly assigned treatment
 with Uro-Vaxom®, or placebo, for 3 months and followed-up for a further 3 months.

 This is to expose any pitfalls or areas requiring re-designing, such as logistics,
 recruitment and compliance rates, in order to refine the protocol of a definitive clinical
 trial.
Inclusion Criteria:

 -  Have a clinical diagnosis of spinal cord injury, multiple sclerosis, transverse
 myelitis or cauda equina damage;

 -  Have had the diagnosis of the spinal pathology for at least 12 months;

 -  Have not had any significant changes in the underlying condition for 12 weeks

 -  Be living in the community (not in residential care)

 -  Aged 18 to 75 years

 -  Have had at least three urinary tract infection episodes treated using anti-biotics
 over the preceding 12 months;

 -  If a woman of child-bearing age, is willing to use contraception for the duration of
 the study

 -  Having the mental capacity to give informed consent

 Exclusion Criteria:

 -  Have had surgical alterations to the bladder, excluding supra-pubic catherisation.

 -  Known hypersensitivity to the active principle or to any of the excipients of
 Uro-Vaxom®

 -  Being unwilling to take a product containing gelatin (e.g. vegetarians)

 -  recruitment can be postponed until antibiotics have not been used for a period of
 14 days and symptoms of a UTI have subsided