Prebiotics for Spinal Cord Injury Patients With Bowel and Bladder Dysfunction
Prebiotics for Spinal Cord Injury Patients With Bowel and Bladder Dysfunction
An investigator initiated pilot study: two arm, double blind, placebo controlled, randomized,
 group of approximately 60 patients with spinal cord injury, and who have evidence of
 neurogenic bladder. Patients will be treated with human milk oligosaccharide (HMO) versus
 placebo over 12 weeks from start of the investigational medication date (approximately 3
 months) to test whether HMO can improve bowel motility in neurogenic bowel and bladder
 patients. Patients in the placebo arm of the study will be offered participation in the open
 label portion of the study immediately after their part in the control group is completed,
 they will receive HMO for 12 weeks. HMO sachets will be administered to determine the safety
 and efficacy of HMO relative to placebo in improving quality of life of neurogenic bowel and
 bladder patients by improving bowel motility and function.
Spinal cord injury (SCI) is a life changing neurologic diagnosis that affects multiple body
 systems. Urinary tract infections (UTIs) are almost a universal complication of SCI with
 bladder dysfunction, and a significant cause of morbidity in those with SCI. Recurrent UTIs
 requires multiple courses of antibiotic therapy, increasing the incidence of
 multidrug-resistant bacteria. While curative antibiotic therapy is transiently effective,
 recurrences are frequent and bladder colonization is inevitable after SCI because of an
 impaired ability to empty the bladder. Meta-analysis of SCI and UTI have shown there is no
 evidence to support the use of prophylactic antibiotics. Although the exact mechanism of
 action is not fully understood, nearly all UTIs are caused by bacteria from the bowel.
 Therefore, addressing the impaired bowel function in SCI patients would not only improve this
 debilitating condition but also reduce UTI's and the need for antibiotic therapy.

 Since prebiotics are metabolised by bacteria in the colon and their by-products promote
 intestinal peristalsis and can relieve constipation, they could represent an effective option
 to treat bowel dysfunction in SCI patients. The study's aim is to improve bowel motility in
 SCI patients with neurogenic bowel impairments by using 2'-O-fucosyllactose and
 lacto-N-neotetraose, novel human milk oligosaccharide (HMO) sugars that have already been
 shown to very specifically modulate intestinal bacteria. In the bowel, the HMO would induce
 an increase in bifidobacteria, which would further produce short chain fatty acids such that
 stimulate bowel motility and other beneficially regarded bacteria.

 The Principal Investigator/Sponsor will test this potential in a pilot clinical study with a
 HMO mix that has shown to promote bifidobacteria (Ellison 2016). These HMO compounds are
 structurally different from the less pure, plant-or bovine dairy-based prebiotics that are
 currently used in other human applications, and are safe, well tolerated, food grade
 substances. They have been shown to soften the stools in healthy adults and reduce
 constipation; therefore, it is expected they will positively impact the quality of life of
 neurogenic bowel and bladder patients by improving bowel motility, and also reducing the
 associated co-morbidity of recurrent urinary tract infections. The study will collect data on
 a sample of up to 60 patients with SCI and neurogenic bowel dysfunction scores of >13.

 The Principal Investigator/Sponsor will assess the HMO's effects on the quality of life,
 intestinal bacterial composition, bowel motility, and associated co-morbidities such as
 urinary tract infections (UTIs). In the longer term this is expected to reduce UTI occurrence
 due to reduced pathogen loading; as a consequence, reduce antibiotic use and levels of drug
 resistant bacteria.If the study If successful, the results outlining its significance could
 be forwarded to the senior management team at the recruiting hospital to be considered as a
 potential management tool in the care of patients with SCI.

 This study will assess faecal and urine samples at four time points for microbiome and other
 analyses at baseline, 4 weeks, 8 weeks (approximately 2 months) and 12 weeks (approximately 3
 months) from the date of starting the study product. Prior to commencing their treatment, and
 at weeks 8 and 12, the research coordinator (blinded to the randomisation) will assess
 patients using various bowel, bladder and quality of life questionnaires during clinic
 visits, at home or by telephone interview.

 The type, level, and completeness of injury will be documented, and the type of bowel and
 bladder dysfunction (upper or lower motor neuron) will be classified and, if necessary,
 updated at each in-person visit. Each participant will be provided with instructions and
 study schedule.

 Protocol compliance will be tested through product count and interviews at each follow-up
 visit. Side effects will be assessed using standardized case report forms at each visit.
 Study visits may be in person or over the phone. Participants will be encouraged to report
 any events they may experience directly to the coordinator.

 Participants who withdraw consent to continue treatments, will be encouraged to undergo the
 planned assessments. Withdrawal at the request of investigators or medical personnel may
 include, but are not limited to:

 1. Symptoms are deemed to be potentially related to the study product

 2. New diagnosis of exclusion criteria;

 3. Unacceptable side effects;

 4. Death

 Estimated time to complete recruitment: Averaging 53 weeks, approximately 12 months
Inclusion Criteria:

 -  18 years old

 -  SCI of at least 3 months duration

 -  Neurogenic bowel dysfunction scores of >13

 Exclusion Criteria:

 -  Pregnancy

 -  Inability to understand and respond to the provided questionnaires

 -  Carcinomas during the last 5 years

 -  Bowel surgery

 -  Crohn ́s disease or other bowel conditions