Impact of Probiotics on Urinary Symptoms in Spinal Cord Injury SCI and SB

• Sponsor: Medstar Health Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02748356
• Collaborator: Patient-Centered Outcomes Research Institute (Other), Children's National Research Institute (Other), Georgetown University (Other)
• Enrollment: 7
• Locations: 2
• Arm: 1
• Actual Duration (Months): 36
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

As a collaborative effort between MedStar National Rehabilitation Hospital (NRH), Children's National Medical Center (CNMC) Department of Urology, Children's Research Institute (CRI) Center for Genetic Medicine Research, Georgetown University, and MedStar Georgetown University Hospital, the overall objective of this study is to develop, validate, and assess a patient-initiated, probiotic-based, selfmanagement protocol that is initiated at the time of urinary symptoms. The self-management protocol will allow patients to manage urinary symptoms and avoid potentially unnecessary antibiotic use, and provide a readily-available means of maintaining health, function, and independence throughout the lifespan.

Condition or Disease	Intervention/Treatment	Phase
Lower Urinary Tract Symptoms	Drug: Lactobacillus	Phase 2

Detailed Description

Lower urinary symptoms are a common issue for individuals with neurogenic bladder, commonly occurring in the Spina bifida and Spinal Cord Injury population. In this study, probiotics will be introduced into the bladder to prevent UTIs. Introduction of probiotics will be determined by a validated symptom questionnaire (USQ-NB) and protocol (SMP-PRO).

This study will estimate the strength of the associations between successful implementation of the probiotic self-management program (USQ-NB and SMP-PRO) and urinary symptoms, bladder inflammation, and the urine microbiome. Investigators will conduct an 18-month study in which each participant will serve as his/her own control through 3 phases of study: 6-months usual care (baseline), 6-months probiotic intervention, and 6-months follow-up.

Participants will complete the Urinary Symptom Questionnaire weekly. After 6 months of baseline data collection, participants will receive the Lactobacillus (Culturelle GG, 20 billion live organisms for adults and 10 billion live organisms for children <18 years of age), will be instructed on preparation and intravesicular instillation of the Lactobacillus, and will have a tutorial with a fellow consumer on use of the patient-initiated protocol. The protocol and Lactobacillus bladder instillation instructions (including a step-by-step video) will be available on the study website for 24/7 access and written instructions will be provided at the time of instruction.

For the intravesicular Lactobacillus instillation, participants will be instructed to mix the contents into sterile saline. After mixing, participants will draw up the liquid Lactobacillus mixture into a 60cc catheter tip syringe and instill via the intermittent catheter after fully emptying the bladder. The amount instilled is determined by the age of the child. Participants will be instructed not to catheterize for at least 4 hours after the bladder instillation. Participants will receive 10 Culturelle GG at the beginning of the treatment phase. At the end of each month, the coordinator or RA will ask how many remaining tablets the participant has, and if needed dispense the next supply of 10 tablets. Participants will be instructed to complete the USQ-NB weekly.

If/when urinary symptoms occur, subjects will be instructed to follow the protocol to determine whether to initiate intravesicular Lactobacillus instillation or be evaluated by a physician. The self-management protocol will also direct them to discontinue Lactobacillus instillation or be evaluated by a physician if symptoms remit, persist (after 2 instillations), or worsen. The maximum number of instillations is 2 over 28 hours. If participants are directed by the self-management protocol to seek medical attention or s/he feels the need for medical evaluation, s/he will be advised to obtain care as they typically would by their health care provider. Participants will be supplied with letters to be brought to their health care provider notifying them of the study and requesting sharing of urinalysis and urine culture results with the research team. A verified UTI will include those that resulted in antibiotic treatment by a health care professional. An additional urine sample for metagenomics will either be left with the health care provider for pick up by the research team, brought to the research site, or obtained by the RA at a mutually convenient site.

After completion of the 6-month patient-initiated self-management protocol intervention period, participants will monitor symptoms weekly using the USQ-NB.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: The Impact of Self-Management With Probiotics on Urinary Symptoms and the Urine Microbiome in Individuals With Spinal Cord Injury (SCI) and Spina Bifida (SB)
• Actual Study Start Date: Jan 1, 2016
• Actual Primary Completion Date: Oct 21, 2018
• Actual Study Completion Date: Dec 31, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Individuals with Spina Bifida Lactobacillus rhamnosus GG

Drug: Lactobacillus; Eligible patients will undergo 1 Lactobacillus pediatric dose (Culturelle GG 10 Billion live organisms) instillation by study personnel at the study site. For the intravesicular Lactobacillus instillation, the contents of 1 Lactobacillus capsule will be mixed into sterile 0.9% saline using an age-based estimate of bladder capacity. Similar to adults, this bladder instillation will represent 10% of the estimated maximum bladder volume based on age.; Other Names: Culturelle

Outcome Measures

Primary Outcome Measures

1. Lactobacillus Safety [months 1-18 of study]

   Total Adverse Events (AE + Serious AE) per participants

Secondary Outcome Measures

1. Lactobacillus Tolerability [months 7-18]

   This is a one-item satisfaction rating. "While thinking only about the preceding 6-month time period: "can you estimate, using a scale from 0 to 100%, whether or not you would seek out this intervention and pay for it yourself if insurance did not pay for it?" Participants indicated their answer by moving a "slider" with three anchors: 0%=Would absolutely never do this; 50%=Might do this; 100%= Would absolutely do this. If a participant is less satisfied, their rating will be lower, and if they are more satisfied, the rating would be higher, but the item did not have options for "better" or "worse". This is not a published scale, we included this item in our general data collection. Ratings averaged over final 12 months of study (Satisfaction question was answered by study participants at 3 time points; 6 months, 12 months and 18 months)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age ≥6 years, and

2. Spina bifida and neuropathic bladder, as determined by the attending physician, and

3. Utilization of intermittent catheterization for bladder management, and

4. History of 2 or more urinary tract infections (UTIs) in the past year, and

5. Community dwelling.

Exclusion Criteria:

1. Has a known genitourinary pathology beyond neuropathic bladder (e.g. vesicoureteral reflux, bladder stones, kidney stones, etc), and/or

2. Uses prophylactic antibiotics, and/or

3. Uses intravesicular agents to reduce UTI (e.g. gentamycin), and/or

4. Has psychologic or psychiatric conditions influencing the ability to follow instructions, and/or

5. Participates in another study in which results would be confounded, and/or

6. Is pregnant or breastfeeding, and/or

7. Has a history of acquired or genetic immunodeficiencies, or active, acute or chronic serious infections (e.g. viral hepatitides, HIV/AIDs), and/or

8. Has cancer or an autoimmune disorder, and/or

9. Has a serious allergy to any component or excipients in the live bacterial combination product, and/or

10. Has had a change in neurologic status in the previous 2 weeks, and/or

11. Has taken antibiotic for any reason in the previous 2 weeks, and/or

12. Has a history of sensitivity or allergy to ampicillin or tetracycline, and/or

13. Has a current urinary tract infection or urinary tract infection within the previous 2 weeks (as defined by Infectious Diseases Society of America CAUTI Guidelines, 2010).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Medical Center	Washington	District of Columbia	United States	20010
2	MedStar National Rehabilitation Hospital	Washington	District of Columbia	United States	20010

Sponsors and Collaborators

• Medstar Health Research Institute
• Patient-Centered Outcomes Research Institute
• Children's National Research Institute
• Georgetown University

Investigators

• Principal Investigator: Hans Pohl, MD, Children's National Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 18, 2017

More Information

Publications

None provided.

• Responsible Party: Medstar Health Research Institute
• ClinicalTrials.gov Identifier: NCT02748356
• Other Study ID Numbers: 5753
• First Posted: Apr 22, 2016
• Last Update Posted: Apr 24, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Medstar Health Research Institute: Spina Bifida; Spinal Cord Injury
• Additional relevant MeSH terms: Spinal Cord Injuries; Lower Urinary Tract Symptoms

Study Results

Participant Flow

Arm/Group Title	Individuals With Spina Bifida or Spinal Cord Injury
Arm/Group Description	Lactobacillus instillation During intervention phase participants were instructed to instill a Lactobacillus solution via their intermittent catheter when they experienced cloudier or more bad- smelling, stronger, fouler or more pungent than their normal urine. These symptoms had to be experienced in the absence of fever, shaking chills, feeling unclear, foggy or confused, overall sense of discomfort, feeling more tired than usual, side pain in the lower back, tenderness to touch in the side of the low back, blood in urine, abdominal pain below, belly button, increase in muscle tightness or tone, autonomic dysreflexia, sense of unease.
Period Title: Overall Study
STARTED	7
COMPLETED	6
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Individuals With Spina Bifida or Spinal Cord Injury
Arm/Group Description	Lactobacillus instillation During intervention phase participants were instructed to instill a Lactobacillus solution via their intermittent catheter when they experienced cloudier or more bad- smelling, stronger, fouler or more pungent than their normal urine. These symptoms had to be experienced in the absence of fever, shaking chills, feeling unclear, foggy or confused, overall sense of discomfort, feeling more tired than usual, side pain in the lower back, tenderness to touch in the side of the low back, blood in urine, abdominal pain below, belly button, increase in muscle tightness or tone, autonomic dysreflexia, sense of unease.
Overall Participants	7
Age (Count of Participants)
<=18 years	7 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	4 57.1%
Male	3 42.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 14.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	6 85.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Lactobacillus Safety
Description	Total Adverse Events (AE + Serious AE) per participants
Time Frame	months 1-18 of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Individuals With Spina Bifida or Spinal Cord Injury
Arm/Group Description	Lactobacillus instillation During intervention phase participants were instructed to instill a Lactobacillus solution via their intermittent catheter when they experienced cloudier or more bad- smelling, stronger, fouler or more pungent than their normal urine. These symptoms had to be experienced in the absence of fever, shaking chills, feeling unclear, foggy or confused, overall sense of discomfort, feeling more tired than usual, side pain in the lower back, tenderness to touch in the side of the low back, blood in urine, abdominal pain below, belly button, increase in muscle tightness or tone, autonomic dysreflexia, sense of unease.
Measure Participants	7
Mean (Standard Deviation) [Adverse Events]	.286 (.488)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Individuals With Spina Bifida or Spinal Cord Injury
	Comments
	Type of Statistical Test	Other
	Comments	1 sample t-test
Statistical Test of Hypothesis	p-Value	=0.351
	Comments
	Method	t-test, 2 sided
	Comments	This is a single group comparison

2. Secondary Outcome

Title	Lactobacillus Tolerability
Description	This is a one-item satisfaction rating. "While thinking only about the preceding 6-month time period: "can you estimate, using a scale from 0 to 100%, whether or not you would seek out this intervention and pay for it yourself if insurance did not pay for it?" Participants indicated their answer by moving a "slider" with three anchors: 0%=Would absolutely never do this; 50%=Might do this; 100%= Would absolutely do this. If a participant is less satisfied, their rating will be lower, and if they are more satisfied, the rating would be higher, but the item did not have options for "better" or "worse". This is not a published scale, we included this item in our general data collection. Ratings averaged over final 12 months of study (Satisfaction question was answered by study participants at 3 time points; 6 months, 12 months and 18 months)
Time Frame	months 7-18

Outcome Measure Data

Analysis Population Description

5 out of 7 children instilled Lactobacillus at least once

Arm/Group Title	Individuals With Spina Bifida or Spinal Cord Injury
Arm/Group Description	Lactobacillus instillation During intervention phase participants were instructed to instill a Lactobacillus solution via their intermittent catheter when they experienced cloudier or more bad- smelling, stronger, fouler or more pungent than their normal urine. These symptoms had to be experienced in the absence of fever, shaking chills, feeling unclear, foggy or confused, overall sense of discomfort, feeling more tired than usual, side pain in the lower back, tenderness to touch in the side of the low back, blood in urine, abdominal pain below, belly button, increase in muscle tightness or tone, autonomic dysreflexia, sense of unease.
Measure Participants	5
Mean (Standard Deviation) [units on a scale]	73.6 (28.3)

Adverse Events

Time Frame	Adverse Events were collected throughout the study (18 months)
Arm/Group Title	Individuals With Spina Bifida or Spinal Cord Injury
Arm/Group Description	Lactobacillus instillation During intervention phase participants were instructed to instill a Lactobacillus solution via their intermittent catheter when they experienced cloudier or more bad- smelling, stronger, fouler or more pungent than their normal urine. These symptoms had to be experienced in the absence of fever, shaking chills, feeling unclear, foggy or confused, overall sense of discomfort, feeling more tired than usual, side pain in the lower back, tenderness to touch in the side of the low back, blood in urine, abdominal pain below, belly button, increase in muscle tightness or tone, autonomic dysreflexia, sense of unease.
All Cause Mortality
	Individuals With Spina Bifida or Spinal Cord Injury
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Individuals With Spina Bifida or Spinal Cord Injury
	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)
Renal and urinary disorders
Urinary tract infection	1/7 (14.3%)	1
Surgical and medical procedures
Tethered spinal cord surgery	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Individuals With Spina Bifida or Spinal Cord Injury
	Affected / at Risk (%)	# Events
Total	0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.