Safety and Effect of L. Reuteri on Biomarkers of Inflammation in Healthy Infants With Colic
Primary Purpose
Gastrointestinal, Colic
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lactobacillus reuteri
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Gastrointestinal focused on measuring Crying, Fussiness, Gas, Hydrogen Breath, Fecal Calprotectin
Eligibility Criteria
Inclusion Criteria:
- Full-term babies with colic (21-90 days old, who cry/fuss > 3h daily x > 3d wk)
- baby must have more than 3h crying for enrollment
Exclusion Criteria:
- severe gastroesophageal reflux (throwing up or spitting up more than a teaspoon of milk > 8 times daily, projectile, bilious or bloody emesis)
- failure to thrive
- intrauterine growth retardation
- hematochezia (blood in the stools)
- diarrhea (watery stools that takes the shape of a container > 5x daily)
- fever (38.2 degrees)
- Premature infants (<37 wk gestation)
Sites / Locations
- University of Texas Health Science Center at Houston
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Lactobacillus reuteri
Sunflower Oil
Arm Description
The first arm of the cohort will include 30 patients on LR (5x10^8 cfu's orally once daily.)
The second arm includes 15 subjects on placebo (sunflower oil.)
Outcomes
Primary Outcome Measures
45 healthy infants with colic will receive LR (health-promoting bacteria) or placebo measuring any changes in their health status.
Physical Examination of infants will be performed to evaluate any adverse effects of LR.
Electrolyte testing at baseline will evaluate for any inborn error of fluid and electrolyte balance and at end of treatment will evaluate for any adverse impact of LR in the subjects.
Secondary Outcome Measures
Determine effect of L. reuteri in 45 infants with colic on gastrointestinal inflammation as assessed by fecal calprotectin.
To examine for evidence of anti-inflammatory effects in the normal intestine, we will test fecal samples from all infants for calprotectin level.
Full Information
NCT ID
NCT01849991
First Posted
January 31, 2013
Last Updated
January 26, 2018
Sponsor
The University of Texas Health Science Center, Houston
1. Study Identification
Unique Protocol Identification Number
NCT01849991
Brief Title
Safety and Effect of L. Reuteri on Biomarkers of Inflammation in Healthy Infants With Colic
Official Title
Safety and Effect of L. Reuteri on Biomarkers of Inflammation in Healthy Infants With Colic
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This protocol is a study of the effects of Lactobacillus reuteri in 45 healthy infants with colic. The study is being conducted in order to prove treatment dose with probiotic (Lactobacillus reuteri) in a clinical setting is safe in healthy infants with colic.
Detailed Description
This study will evaluate the safety and tolerability of Lactobacillus reuteri in healthy infants with colic. Patients will be randomized to receive either L. reuteri at one dose orally for a total of 42 doses. The doses will be 5x108 (5 drops) during a satisfactory assessment of safety and tolerability. The time on study treatment is 6 months, and the target sample size is 45 healthy infants.
Secondly, the investigators aim to gather evidence supporting hypothesis of safety and tolerability of Lactobacillus reuteri by administering a physical examination and testing of complete blood count, liver tests, and serum electrolytes over a forty-two day period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal, Colic
Keywords
Crying, Fussiness, Gas, Hydrogen Breath, Fecal Calprotectin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lactobacillus reuteri
Arm Type
Active Comparator
Arm Description
The first arm of the cohort will include 30 patients on LR (5x10^8 cfu's orally once daily.)
Arm Title
Sunflower Oil
Arm Type
Placebo Comparator
Arm Description
The second arm includes 15 subjects on placebo (sunflower oil.)
Intervention Type
Biological
Intervention Name(s)
Lactobacillus reuteri
Intervention Description
Lactobacillus reuteri oil drops are a natural product containing Lactobacillus reuteri (LR), which has traditionally been used for the establishment of a well-functioning gastrointestinal (GI) microbiota and prevention and treatment of mild diarrhea associated with GI-tract infections, travel or antibiotic treatment.
The drug is a clear liquid when suspended in sunflower oil. The drug will be administered orally, 0.2cc once daily.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo is sunflower oil (vehicle for LR). The placebo will be administered the same way as drug listed above.
Primary Outcome Measure Information:
Title
45 healthy infants with colic will receive LR (health-promoting bacteria) or placebo measuring any changes in their health status.
Description
Physical Examination of infants will be performed to evaluate any adverse effects of LR.
Electrolyte testing at baseline will evaluate for any inborn error of fluid and electrolyte balance and at end of treatment will evaluate for any adverse impact of LR in the subjects.
Time Frame
92 days
Secondary Outcome Measure Information:
Title
Determine effect of L. reuteri in 45 infants with colic on gastrointestinal inflammation as assessed by fecal calprotectin.
Description
To examine for evidence of anti-inflammatory effects in the normal intestine, we will test fecal samples from all infants for calprotectin level.
Time Frame
1, 42 & 92 days
Other Pre-specified Outcome Measures:
Title
Measuring the change in crying times (Barr Diary) in 45 healthy infants with colic during the administration of L reuteri.
Description
Clinical scoring of crying and fussing will be evaluated using the Barr diary which will show crying patterns.
Time Frame
92 days
Title
Determine effects of L. reuteri in 45 healthy infants with colic measuring the immunologic responses with plasma cytokines and circulating regulatory T-cells.
Description
A panel of inflammatory biomarkers will be examined which includes Th1 cytokines (TNFα, IL-1β); a Th2 cytokine (IL-10), a cytokine which regulates maturation of Tregs (IL-2), a cytokine receptor (OPG), a marker of intestinal barrier function (TIMP-1) and a marker for autoimmunity (TWEAK). Biomarkers will be assessed by MSD human multiplex cytokine assays or R&D Human ELISA kit.
We will determine if LR treatment affects the frequency of Tregs in PBMCs in normal babies with colic.
Time Frame
1& 42 days
Title
Determine effect of L. reuteri on gastrointestinal inflammation as assessed by fecal microbiota in 45 healthy infants with colic.
Description
A stool sample will be collected and analyzed to determine the effect on overall microbiota produced by the ingestion of LR.
Time Frame
1, 42 & 92 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Weeks
Maximum Age & Unit of Time
3 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Full-term babies with colic (21-90 days old, who cry/fuss > 3h daily x > 3d wk)
baby must have more than 3h crying for enrollment
Exclusion Criteria:
severe gastroesophageal reflux (throwing up or spitting up more than a teaspoon of milk > 8 times daily, projectile, bilious or bloody emesis)
failure to thrive
intrauterine growth retardation
hematochezia (blood in the stools)
diarrhea (watery stools that takes the shape of a container > 5x daily)
fever (38.2 degrees)
Premature infants (<37 wk gestation)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J. Marc Rhoads, M.D.
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28969890
Citation
Fatheree NY, Liu Y, Taylor CM, Hoang TK, Cai C, Rahbar MH, Hessabi M, Ferris M, McMurtry V, Wong C, Vu T, Dancsak T, Wang T, Gleason W, Bandla V, Navarro F, Tran DQ, Rhoads JM. Lactobacillus reuteri for Infants with Colic: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. J Pediatr. 2017 Dec;191:170-178.e2. doi: 10.1016/j.jpeds.2017.07.036. Epub 2017 Sep 29.
Results Reference
result
PubMed Identifier
30177353
Citation
Rhoads JM, Collins J, Fatheree NY, Hashmi SS, Taylor CM, Luo M, Hoang TK, Gleason WA, Van Arsdall MR, Navarro F, Liu Y. Infant Colic Represents Gut Inflammation and Dysbiosis. J Pediatr. 2018 Dec;203:55-61.e3. doi: 10.1016/j.jpeds.2018.07.042. Epub 2018 Aug 31.
Results Reference
derived
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Safety and Effect of L. Reuteri on Biomarkers of Inflammation in Healthy Infants With Colic
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