Prebiotics for Spinal Cord Injury Patients With Bowel and Bladder Dysfunction

NCT ID: NCT03987126

Last Updated: 2023-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-27

Study Completion Date

2023-10-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Spinal Cord Injuries Neurogenic Bowel Bladder Dysfunction

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

One placebo arm and one active treatment arm, participants will be assigned to each arm equally based on their Neurogenic Bowel Dysfunction score.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
No other parties will be masked for the study. A part of the study will be open label.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Human Milk Oligosaccharide (HMO)

10 g sachet, self-administered for 3 months.

2'-O-fucosyllactose and lacto-N-neotetraose, novel human milk oligosaccharide (HMO) sugars have already been shown to very specifically modulate intestinal bacteria, namely the beneficially viewed bifidobacteria, in clinical studies in adults. Modulating bifidobacteria increases the levels of specific short chain fatty acids (SCFAs), such as butyrate, propionate and acetate.These SCFAs have been shown to stimulate colonic sodium and fluid absorption and exert proliferative effects on the colonocyte in experimental animal studies since the 1990s (Scheppach 1994). Therefore, increasing their levels would lead to an improvement in intestinal motility, as has been summarised previously (Koh 2016)

Group Type ACTIVE_COMPARATOR

Human Milk Oligosaccharides (HMO)

Intervention Type DIETARY_SUPPLEMENT

Sachet containing 10 grams of HMO

Placebo

10 g sachet, self-administered for 3 months.

Placebo sachets are identical to the HMO sachets in color, taste, smell, size and shape

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Sachet manufactured to mimic 10g of HMO

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Human Milk Oligosaccharides (HMO)

Sachet containing 10 grams of HMO

Intervention Type DIETARY_SUPPLEMENT

Placebo

Sachet manufactured to mimic 10g of HMO

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Placebo for HMO

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

The W. Garfield Weston Foundation

UNKNOWN

Sponsor Role collaborator

St. Joseph's Health Care London

OTHER

Sponsor Role collaborator

Parkwood Hospital, London, Ontario

OTHER

Sponsor Role collaborator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jeremy P Burton, PhD

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Parkwood Institute

London, Ontario, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Canada

References

Explore related publications, articles, or registry entries linked to this study.

Taweel WA, Seyam R. Neurogenic bladder in spinal cord injury patients. Res Rep Urol. 2015 Jun 10;7:85-99. doi: 10.2147/RRU.S29644. eCollection 2015.

Reference Type BACKGROUND
PMID: 26090342 (View on PubMed)

Krogh K, Christensen P, Sabroe S, Laurberg S. Neurogenic bowel dysfunction score. Spinal Cord. 2006 Oct;44(10):625-31. doi: 10.1038/sj.sc.3101887. Epub 2005 Dec 13.

Reference Type BACKGROUND
PMID: 16344850 (View on PubMed)

Christensen P, Bazzocchi G, Coggrave M, Abel R, Hultling C, Krogh K, Media S, Laurberg S. A randomized, controlled trial of transanal irrigation versus conservative bowel management in spinal cord-injured patients. Gastroenterology. 2006 Sep;131(3):738-47. doi: 10.1053/j.gastro.2006.06.004.

Reference Type BACKGROUND
PMID: 16952543 (View on PubMed)

Christensen P, Bazzocchi G, Coggrave M, Abel R, Hulting C, Krogh K, Media S, Laurberg S. Outcome of transanal irrigation for bowel dysfunction in patients with spinal cord injury. J Spinal Cord Med. 2008;31(5):560-7. doi: 10.1080/10790268.2008.11754571.

Reference Type BACKGROUND
PMID: 19086714 (View on PubMed)

Tulsky DS, Kisala PA, Tate DG, Spungen AM, Kirshblum SC. Development and psychometric characteristics of the SCI-QOL Bladder Management Difficulties and Bowel Management Difficulties item banks and short forms and the SCI-QOL Bladder Complications scale. J Spinal Cord Med. 2015 May;38(3):288-302. doi: 10.1179/2045772315Y.0000000030.

Reference Type BACKGROUND
PMID: 26010964 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27719686 (View on PubMed)

Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016 Jun 2;165(6):1332-1345. doi: 10.1016/j.cell.2016.05.041.

Reference Type BACKGROUND
PMID: 27259147 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29155236 (View on PubMed)

Bao Y, Al KF, Chanyi RM, Whiteside S, Dewar M, Razvi H, Reid G, Burton JP. Questions and challenges associated with studying the microbiome of the urinary tract. Ann Transl Med. 2017 Jan;5(2):33. doi: 10.21037/atm.2016.12.14.

Reference Type BACKGROUND
PMID: 28217698 (View on PubMed)

Reid G, Burton JP. Urinary incontinence: Making sense of the urinary microbiota in clinical urology. Nat Rev Urol. 2016 Oct;13(10):567-8. doi: 10.1038/nrurol.2016.182. Epub 2016 Sep 20. No abstract available.

Reference Type BACKGROUND
PMID: 27644934 (View on PubMed)

Whiteside SA, Razvi H, Dave S, Reid G, Burton JP. The microbiome of the urinary tract--a role beyond infection. Nat Rev Urol. 2015 Feb;12(2):81-90. doi: 10.1038/nrurol.2014.361. Epub 2015 Jan 20.

Reference Type BACKGROUND
PMID: 25600098 (View on PubMed)

Scheppach W. Effects of short chain fatty acids on gut morphology and function. Gut. 1994 Jan;35(1 Suppl):S35-8. doi: 10.1136/gut.35.1_suppl.s35.

Reference Type BACKGROUND
PMID: 8125387 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://rickhanseninstitute.org/e-scan-atlas

The first canadian national atlas of Spinal Cord Injury Rehabilitation from a collaborative community of practice to provide the best care to individuals living with the consequences of spinal cord injury.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

6170

Identifier Type: -

Identifier Source: org_study_id