Clinical trial NCT03987126: Prebiotics for Spinal Cord Injury Patients With Bowel and Bladder Dysfunction
Official title: Use of Novel Human Milk Prebiotics to Improve the Quality of Life for Spinal Cord Injury Patients With Bowel and Bladder Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spinal Cord Injuries
Neurogenic Bowel
Bladder Dysfunction
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: The W. Garfield Weston Foundation
name: St. Joseph's Health Care London
name: Parkwood Hospital, London, Ontario
First posted: 2019-06-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: One placebo arm and one active treatment arm, participants will be assigned to each arm equally based on their Neurogenic Bowel Dysfunction score.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* 18 years old
* SCI of at least 3 months duration
* Neurogenic bowel dysfunction scores of \>10 OR 4 or less bowel movements per week, OR requires a suppository to have a bowel movement

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

Primary outcomes:
measure: Bowel motility
timeFrame: 12 weeks
measure: Neurogenic bowel dysfunction score (NBD)
timeFrame: 12 weeks
measure: Change in method of bowel assistance
timeFrame: 12 weeks
measure: Duration of bowel routine
timeFrame: 12 weeks
measure: Episodes of incontinence
timeFrame: 12 weeks
measure: Frequency of bowel movements per week
timeFrame: 12 weeks
Secondary outcomes:
measure: Microbiome changes from baseline to end of study
timeFrame: 12 weeks
measure: Changes in pain
timeFrame: 12 weeks
measure: Change in sleep
timeFrame: 12 weeks
measure: Change in mood
timeFrame: 12 weeks
measure: Quality of Life Measures survey
timeFrame: 12 weeks
measure: Number of participants reporting unexpected adverse events
timeFrame: 12 weeks
Other outcomes:
Locations:
city: London
country: Canada
facility: Parkwood Institute
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Jeremy P Burton, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Elison E, Vigsnaes LK, Rindom Krogsgaard L, Rasmussen J, Sorensen N, McConnell B, Hennet T, Sommer MO, Bytzer P. Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota. Br J Nutr. 2016 Oct;116(8):1356-1368. doi: 10.1017/S0007114516003354. Epub 2016 Oct 10.
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citation: Al KF, Bisanz JE, Gloor GB, Reid G, Burton JP. Evaluation of sampling and storage procedures on preserving the community structure of stool microbiota: A simple at-home toilet-paper collection method. J Microbiol Methods. 2018 Jan;144:117-121. doi: 10.1016/j.mimet.2017.11.014. Epub 2017 Nov 16.
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