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Prebiotics for Spinal Cord Injury Patients With Bowel and Bladder Dysfunction

Primary Purpose

Spinal Cord Injuries, Neurogenic Bowel, Bladder Dysfunction

Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Human Milk Oligosaccharides (HMO)
Placebo
Sponsored by
Lawson Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Cord Injuries

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Parkwood InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Human Milk Oligosaccharide (HMO)

Placebo

Arm Description

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)

10 g sachet, self-administered for 3 months. Placebo sachets are identical to the HMO sachets in color, taste, smell, size and shape

Outcomes

Primary Outcome Measures

Bowel motility
Improvement of 25-30% in our study population in the neurogenic bowel function of our intervention study group after treatment, will be measured by the Neurogenic Bowel dysfunction score. Neurogenic Bowel Dysfunction score will be measured by a symptom-based questionnaire that scores 10 variables to attain a total score between 0 and 47. It includes frequency of bowel movements, time of defecation, evacuation and incontinence.
Neurogenic bowel dysfunction score (NBD)
The change in this assessment from baseline to end of study will help determine the improvement in bowel motility. It is a symptom-based questionnaire that scores 10 variables to attain a total score between 0 and 47. It includes frequency of bowel movements, time of defecation, evacuation and incontinence.
Change in method of bowel assistance
Medications required, home remedies used, other methods of assistance will be recorded in a study questionnaire.
Duration of bowel routine
Measured by the NBD questionnaire.
Episodes of incontinence
Will be measured in time between bowel movements by the NBD questionnaire.
Frequency of bowel movements per week
Will be measured by the NBD questionnaire.

Secondary Outcome Measures

Microbiome changes from baseline to end of study
Changes in the entire bacterial community from baseline to end of study will be assessed in the lab from faecal and urine samples collected by the participant. The microbes may vary by participant and the study will be looking at which ones present themselves in each case. Of particular interest may be the Enterobacteriaceae like Escherichia coli that cause UTI. Units of measure via culture are colony forming units per g (cfu/g).
Changes in pain
A modified International Spinal Cord Injury Pain Basic Dataset version 2.0 questionnaire will be used. The first part of the questionnaire is a scale that ranges from 1-10, with 1 stating their pain is not interfering with their daily activities, and 10 stating extreme interference. The second part is a table that lists different areas of the body and has the participant check off whether they feel pain in the right, middle, or left side of each body area. Pain type will be assessed by the referring clinician and documented in a study CRF.
Change in sleep
will be documented in the International Spinal Cord Injury Pain Basic Dataset v2.0 questionnaire. The question scales from 1 - 10, 1 stating that pain has had no interference with the participant getting a good night's sleep, and 10 stating major interference.
Change in mood
will be documented in the International Spinal Cord Injury Pain Basic Dataset v2.0 questionnaire. The answer will be measured in a scale from 1-10, 1 stating that pain has had no interference with their mood, and 10 stating major interference.
Quality of Life Measures survey
a general quality of life measures survey will be included in the study. The QOLS is scored by adding up the score on each item to yield a total score for the instrument. The cale includes 16 questions, each question can be answered from a range of 1-7 (1 being very unhappy, 7 being very happy) Scores can range from 16 to 112.
Number of participants reporting unexpected adverse events
Adverse events will be recorded through case report forms and reported to the principal investigator. Side effects will be assessed using standardized case report forms at each visit. Participants are encouraged to contact the coordinator to report any concerns.

Full Information

First Posted
June 4, 2019
Last Updated
August 30, 2023
Sponsor
Lawson Health Research Institute
Collaborators
The W. Garfield Weston Foundation, St. Joseph's Health Care London, Parkwood Hospital, London, Ontario
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1. Study Identification

Unique Protocol Identification Number
NCT03987126
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 27, 2021 (Actual)
Primary Completion Date
June 29, 2023 (Actual)
Study Completion Date
October 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lawson Health Research Institute
Collaborators
The W. Garfield Weston Foundation, St. Joseph's Health Care London, Parkwood Hospital, London, Ontario

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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: Symptoms are deemed to be potentially related to the study product New diagnosis of exclusion criteria; Unacceptable side effects; Death Estimated time to complete recruitment: Averaging 53 weeks, approximately 12 months

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries, Neurogenic Bowel, Bladder Dysfunction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigator
Masking Description
No other parties will be masked for the study. A part of the study will be open label.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Human Milk Oligosaccharide (HMO)
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
10 g sachet, self-administered for 3 months. Placebo sachets are identical to the HMO sachets in color, taste, smell, size and shape
Intervention Type
Dietary Supplement
Intervention Name(s)
Human Milk Oligosaccharides (HMO)
Intervention Description
Sachet containing 10 grams of HMO
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo for HMO
Intervention Description
Sachet manufactured to mimic 10g of HMO
Primary Outcome Measure Information:
Title
Bowel motility
Description
Improvement of 25-30% in our study population in the neurogenic bowel function of our intervention study group after treatment, will be measured by the Neurogenic Bowel dysfunction score. Neurogenic Bowel Dysfunction score will be measured by a symptom-based questionnaire that scores 10 variables to attain a total score between 0 and 47. It includes frequency of bowel movements, time of defecation, evacuation and incontinence.
Time Frame
12 weeks
Title
Neurogenic bowel dysfunction score (NBD)
Description
The change in this assessment from baseline to end of study will help determine the improvement in bowel motility. It is a symptom-based questionnaire that scores 10 variables to attain a total score between 0 and 47. It includes frequency of bowel movements, time of defecation, evacuation and incontinence.
Time Frame
12 weeks
Title
Change in method of bowel assistance
Description
Medications required, home remedies used, other methods of assistance will be recorded in a study questionnaire.
Time Frame
12 weeks
Title
Duration of bowel routine
Description
Measured by the NBD questionnaire.
Time Frame
12 weeks
Title
Episodes of incontinence
Description
Will be measured in time between bowel movements by the NBD questionnaire.
Time Frame
12 weeks
Title
Frequency of bowel movements per week
Description
Will be measured by the NBD questionnaire.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Microbiome changes from baseline to end of study
Description
Changes in the entire bacterial community from baseline to end of study will be assessed in the lab from faecal and urine samples collected by the participant. The microbes may vary by participant and the study will be looking at which ones present themselves in each case. Of particular interest may be the Enterobacteriaceae like Escherichia coli that cause UTI. Units of measure via culture are colony forming units per g (cfu/g).
Time Frame
12 weeks
Title
Changes in pain
Description
A modified International Spinal Cord Injury Pain Basic Dataset version 2.0 questionnaire will be used. The first part of the questionnaire is a scale that ranges from 1-10, with 1 stating their pain is not interfering with their daily activities, and 10 stating extreme interference. The second part is a table that lists different areas of the body and has the participant check off whether they feel pain in the right, middle, or left side of each body area. Pain type will be assessed by the referring clinician and documented in a study CRF.
Time Frame
12 weeks
Title
Change in sleep
Description
will be documented in the International Spinal Cord Injury Pain Basic Dataset v2.0 questionnaire. The question scales from 1 - 10, 1 stating that pain has had no interference with the participant getting a good night's sleep, and 10 stating major interference.
Time Frame
12 weeks
Title
Change in mood
Description
will be documented in the International Spinal Cord Injury Pain Basic Dataset v2.0 questionnaire. The answer will be measured in a scale from 1-10, 1 stating that pain has had no interference with their mood, and 10 stating major interference.
Time Frame
12 weeks
Title
Quality of Life Measures survey
Description
a general quality of life measures survey will be included in the study. The QOLS is scored by adding up the score on each item to yield a total score for the instrument. The cale includes 16 questions, each question can be answered from a range of 1-7 (1 being very unhappy, 7 being very happy) Scores can range from 16 to 112.
Time Frame
12 weeks
Title
Number of participants reporting unexpected adverse events
Description
Adverse events will be recorded through case report forms and reported to the principal investigator. Side effects will be assessed using standardized case report forms at each visit. Participants are encouraged to contact the coordinator to report any concerns.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexandria Roa Agudelo
Phone
519-646-6100
Ext
42696
Email
Alexandria.RoaAgudelo@sjhc.london.on.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Jeremy P Burton, PhD
Phone
519-646-6000
Ext
61365
Email
Jeremy.Burton@LawsonResearch.Com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy P Burton, PhD
Organizational Affiliation
Lawson Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Parkwood Institute
City
London
State/Province
Ontario
ZIP/Postal Code
N6C0A7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandria Roa Agudelo, MLA/T
Phone
519-646-6100
Ext
42696
Email
Alexandria.RoaAgudelo@sjhc.london.on.ca
First Name & Middle Initial & Last Name & Degree
Eldon Loh, MD
Phone
519-685-4080
Email
Eldon.Loh@sjhc.london.on.ca

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26090342
Citation
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.
Results Reference
background
PubMed Identifier
16344850
Citation
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.
Results Reference
background
PubMed Identifier
16952543
Citation
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.
Results Reference
background
PubMed Identifier
19086714
Citation
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.
Results Reference
background
PubMed Identifier
26010964
Citation
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.
Results Reference
background
PubMed Identifier
27719686
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.
Results Reference
background
PubMed Identifier
27259147
Citation
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.
Results Reference
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PubMed Identifier
29155236
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.
Results Reference
background
PubMed Identifier
28217698
Citation
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.
Results Reference
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PubMed Identifier
27644934
Citation
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.
Results Reference
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PubMed Identifier
25600098
Citation
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.
Results Reference
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PubMed Identifier
8125387
Citation
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.
Results Reference
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Links:
URL
https://rickhanseninstitute.org/e-scan-atlas
Description
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.

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Prebiotics for Spinal Cord Injury Patients With Bowel and Bladder Dysfunction

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