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

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ClinicalTrials.gov Identifier: NCT02748317
Recruitment Status : Active, not recruiting
First Posted : April 22, 2016
Last Update Posted : December 21, 2018
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
Georgetown University
Children's Research Institute
Information provided by (Responsible Party):
Medstar Health Research Institute

Brief Summary:
As a collaborative effort between MedStar National Rehabilitation Hospital (NRH)/MedStar Health Research Institute (MHRI), Children's National Medical Center (CNMC) Department of Urology, Children's Research Institute (CRI) Center for Genetic Medicine Research, and Georgetown University Medical Center, the overall objective of this study is to develop, validate, and assess a patient-initiated, probiotics-based, self management 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 rhamnosus GG 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. 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 for the final 6-month phase of the 18-month study.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 96 participants
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 : January 2016
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2018


Arm Intervention/treatment
Experimental: Adults with Spinal Cord Injury
Lactobacillus rhamnosus GG
Drug: Lactobacillus rhamnosus GG
For the intravesicular Lactobacillus instillation, participants will be instructed to mix the contents of 1 Lactobacillus capsule into 45 cc sterile 0.9% saline.5,6 After mixing, participants will draw up the 45 cc of the liquid Lactobacillus mixture into a 60cc catheter tip syringe and instill via the intermittent catheter after the last catheterization prior to going to bed. Participants will receive 10 Lactobacillus GG tabs at the beginning of 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.
Other Name: Culturelle




Primary Outcome Measures :
  1. Urine Symptom Questionnaire [ Time Frame: Completed Weekly throughout the study (up to 78 weeks) ]
    A preliminary urinary symptom questionnaire has been developed with consumer input based on the most common typical and SCI-specific urinary symptoms.


Secondary Outcome Measures :
  1. Health History Questionnaire [ Time Frame: Collected at Baseline ]
    After subjects give consent, a brief medical history will be conducted using a structured questionnaire including demographic information, genitourinary history, and current medications

  2. Patient satisfaction [ Time Frame: End of each phase (weeks 26, 52, and 78) ]
    Investigators have developed a simple four item patient satisfaction "survey" that will be requested at the end of each phase of the study. Participants will be asked to rate their satisfaction, thinking only about the preceding time period, with changes in the frequency of their symptoms; the amelioration of the severity of their symptoms; and changes in the impact of their symptoms.

  3. Urine Acquisition [ Time Frame: Up to 18 months: collected at Baseline, two times when study subject experiences urinary symptoms, and follow-up after either lactobacillus treatment or antibiotics (not specific time points), and week 12 of follow-up phase ]
    A 50-100 ml urine sample will be collected from each subject for (1) urinalysis and cultivation, and (2) urine microbiome by SMRT sequencing. Urine will be collected from a new, unused intermittent catheter.

  4. Urinalysis [ Time Frame: Up to 18 months: collected at Baseline, two times when study subject experiences urinary symptoms, and follow-up after either lactobacillus treatment or antibiotics (not specific time points), and week 12 of follow-up phase ]
    Urine samples will be assessed utilizing standard clinical microbiology semiquantitative chemical testing using commercial disposable test strips for glucose, bilirubin, ketone, specific gravity, blood pH, protein, urobilinogen, nitrite, and leukocyte esterase. After centrifuging for 5 minutes, microscopic examination for and quantification of WBCs, RBCs, epithelial cells, yeast, bacteria, Trichomonas vaginalis, sperm cells, mucous filaments and crystals will be performed using standard microbial techniques.

  5. Urine Culture [ Time Frame: Up to 18 months: collected at Baseline, two times when study subject experiences urinary symptoms, and follow-up after either lactobacillus treatment or antibiotics (not specific time points), and week 12 of follow-up phase ]
    Standard urine culture microbiology will be performed. A measured amount is inoculated to each of the appropriate media. A calibrated loop designed to deliver a known volume (0.0 I ml per loopful) of urine is used. The sample will be mixed the thoroughly and the top of the container removed. A calibrated wire-inoculating loop is flamed and allowed to cool without coming in contact with any surface. The sterile loop is inserted into the urine sample vertically and urine is allowed to adhere to the loop. The loopful of urine is inoculated over MacConkey agar plates using standard methods. Similarly, a second loopful is collected and inoculated on a blood agar plate. The plates are incubated aerobically at 35-37oC for at least 24 hours. The colonies and colony forming units (CFUs) are counted by multiplying with 100 (since 0.01 ml loop was used).

  6. Microbiome SMRT Sequencing [ Time Frame: Up to 18 months: collected at Baseline, two times when study subject experiences urinary symptoms, and follow-up after either lactobacillus treatment or antibiotics (not specific time points), and week 12 of follow-up phase ]
    Thawed urine samples will be clarified by low-speed centrifugation and bacterial genomic DNA will be isolated from pelleted bacteria using a DNeasy tissue extraction kit (Qiagen) according to manufacturer's instruction. 16S rRNA genes will be amplified. These amplification products will be used for sequencing template preparation using DNA Template Prep Kit 2.0 (Pacific Biosciences) followed by DNA Polymerase binding (DNA Polymerase Binding Kit P4, Pacific Biosciences). Sequenced rRNA genes will be analyzed and classified using Pathoscope.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age≥18 years
  2. SCI, SB or MS at least 1-year duration
  3. Neuropathic bladder, as determined by the attending physician
  4. Utilizing intermittent catheterization for bladder management
  5. A history of 2 or more UTIs in the past year
  6. Community dwelling.

Exclusion Criteria:

  1. Known genitourinary pathology beyond neuropathic bladder (i.e., vesicoureteral reflux, bladder or kidney stones, etc.)
  2. Use of prophylactic antibiotics
  3. Instillation of intravesicular agents to reduce UTI (i.e., gentamycin)
  4. Psychologic or psychiatric conditions influencing the ability to follow instructions
  5. Participation in another study in which results would be confounded
  6. Pregnant or breastfeeding
  7. Individuals with a history of acquired or genetic immunodeficiencies; active, acute or chronic serious infections (i.g., viral hepatitides, HIV/AIDs)
  8. Individuals with cancer/autoimmune disorders
  9. Serious allergy to any component or excipients in the live bacterial combination product
  10. No change in neurologic status in the previous 2 weeks
  11. Taken antibiotic for any reason in the previous 2 weeks
  12. Any patient with history of sensitivity or allergy to ampicillin or tetracycline
  13. Current urinary tract infection or urinary tract infection within the previous 2 weeks (as defined by Infectious Diseases Society of America CAUTI Guidelines, 2010).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02748317


Locations
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United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
MedStar National Rehabilitation Hospital
Washington, District of Columbia, United States, 20010
Sponsors and Collaborators
Medstar Health Research Institute
Patient-Centered Outcomes Research Institute
Georgetown University
Children's Research Institute
Investigators
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Principal Investigator: Suzanne L Groah, MD, MSPH MedStar National Rehabilitation Hospital

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Responsible Party: Medstar Health Research Institute
ClinicalTrials.gov Identifier: NCT02748317     History of Changes
Other Study ID Numbers: 2014-211
First Posted: April 22, 2016    Key Record Dates
Last Update Posted: December 21, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Medstar Health Research Institute:
Spina Bifida
Spinal Cord Injury
Lower Urinary Tract Symptoms
Probiotics
Intermittent Catheterization
Additional relevant MeSH terms:
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Spinal Cord Injuries
Lower Urinary Tract Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Urological Manifestations
Signs and Symptoms