Biological Markers, Bloodstream Infections, Development, Nutrition, Short Bowel Syndrome
Conditions
Keywords
Short Bowel Syndrome, Necrotizing Entercolitis (NEC), Atresia, Parenteral Nutrition, Biological Markers, Growth
Brief summary
The purpose of this research study is to evaluate the effects (good and bad) of supplementation with Glutamine to that of a placebo (L-alanine), on your child and their Short Bowel Syndrome. Researchers are doing this study to see if the addition of Glutamine to oral/tube feeding (nutrition therapy) will work better by preventing bloodstream infections, improving growth, and/or changing the make-up of bacteria in your child's intestine. Glutamine is approved by the FDA for use in adults with Short Bowel Syndrome. In this study, the investigators will be assessing how well Glutamine affects Short Bowel Syndrome in children.
Detailed description
This is a double-blind, randomized placebo-controlled pilot study to investigate the efficacy of enteral glutamine (GLN) supplementation in 36 infants, ≤ 12 months of age with parenteral nutrition (PN)-dependent short bowel syndrome (SBS) due to massive small bowel resection for NEC and/or atresia on improving weaning of PN and preventing infections. The investigators intend to evaluate the effect of enteral feeding and GLN supplementation on the gut bacteria. The investigators will also recruit 12 age-matched controls to evaluate the normal gut bacteria.
Interventions
DRUGGlutamine
0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)
DIETARY_SUPPLEMENTL-alanine
0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 day (6 months)
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emmaus Medical, Inc.
University of Michigan
Emory University
University of Colorado, Denver
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 12 Months
Healthy volunteers
Yes
Inclusion criteria
for Controls: * Less than or equal to 12 months of age * Normal small bowel length without any intestinal resection or primary intestinal disease * Not currently on Total Parenteral Nutrition (TPN) and if ever on TPN this should have been discontinued for at least 4 weeks.
Exclusion criteria
for Controls: * Major congenital or chromosomal anomalies * Inability to tolerate enteral nutrition/regular cow's milk, breast milk or formula * History of liver/intestinal transplantation Inclusion Criteria for Glutamine and Placebo Group of Short Bowel Syndrome (SBS) Patients: * Less than or equal to 12 months of age * Patients who have undergone small bowel resection due to necrotizing enterocolitis (NEC) or intestinal atresia with known small bowel length * Patients who have been Parenteral Nutrition (PN) dependent for more than 42 consecutive days and currently on TPN at time of enrollment * Patients who have the ability to take partial enteral nutrition or breast milk or elemental formula to allow the appropriate dose of glutamine or placebo * Signed informed consent for the use of Glutamine or placebo
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bloodstream Infections (BSI) | 6 months | Evaluate the efficacy of enteral Glutamine supplementation to decrease bloodstream infections in participants that are parenteral nutrition dependent with Short Bowel Syndrome due to necrotizing enterocolitis (NEC) and/or atresia. |
| Length Velocity | 6 months | Assess the efficacy of 6 months of therapy with enteral Glutamine on length velocity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Head Circumference | 6 months | Assess the efficacy of 6 months of therapy with enteral Glutamine on head circumference |
| Mid Arm Circumference | 6 months | Assess the efficacy of 6 months of therapy with enteral Glutamine on mid arm circumference. |
| Weight Velocity | 6 months | Assess the efficacy of 6 months of therapy with enteral Glutamine on weight velocity. |
Countries
United States
Participant flow
Recruitment details
One participant consented and then withdrew prior completing any study procedure. This participant is not included in the participant flow due to the fact no study procedures or randomization occurred.
Participants by arm
| Arm | Count |
|---|---|
| Glutamine L-Glutamine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months) | 2 |
| Placebo L-Alanine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months) | 3 |
| Healthy Control No Intervention - Healthy age-matched infants provided stools on 4 occasions, each separated by 60 days. | 4 |
| Total | 9 |
Baseline characteristics
| Characteristic | Total | Healthy Control | Placebo | Glutamine |
|---|---|---|---|---|
| Age, Customized 11 months through 12 months | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 3 months through 4 months | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Age, Customized 5 months through 6 months | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Customized 6 weeks through 2 months | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Age, Customized 7 months through 8 months | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Customized 9 months through 10 months | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Birth Weight | 2.35 kilograms | — | 2.6 kilograms | 2.4 kilograms |
| Bowel Length | 69.0 Centimeters | — | 82.0 Centimeters | 49.5 Centimeters |
| Cause of Short Bowel Resection Atresia | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Cause of Short Bowel Resection NEC and Atresia | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Cause of Short Bowel Resection Necrotizing enterocolitis (NEC) | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 4 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 2 / 2 | 3 / 3 | 0 / 4 |
| serious Total, serious adverse events | 1 / 2 | 2 / 3 | 0 / 4 |
Outcome results
Primary
Length Velocity
Assess the efficacy of 6 months of therapy with enteral Glutamine on length velocity.
Time frame: 6 months
Population: The number analyzed at Baseline and days 60, 120 and 180 differ from the overall number analyzed due protocol noncompliance and participant request to withdrawal from the protocol. Healthy controls were not analyzed in this outcome measure because they did not receive parenteral nutrition, L-Glutamine or placebo.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Glutamine | Length Velocity | Length at Baseline | 60.9 Centimeters |
| Glutamine | Length Velocity | Length at Day 60 | 62.2 Centimeters |
| Glutamine | Length Velocity | Length at Day 120 | 66.8 Centimeters |
| Glutamine | Length Velocity | Length at Day 180 | 68 Centimeters |
| Placebo | Length Velocity | Length at Day 180 | 78.2 Centimeters |
| Placebo | Length Velocity | Length at Baseline | 66.0 Centimeters |
| Placebo | Length Velocity | Length at Day 120 | 73.7 Centimeters |
| Placebo | Length Velocity | Length at Day 60 | 67.5 Centimeters |
Primary
Number of Participants With Bloodstream Infections (BSI)
Evaluate the efficacy of enteral Glutamine supplementation to decrease bloodstream infections in participants that are parenteral nutrition dependent with Short Bowel Syndrome due to necrotizing enterocolitis (NEC) and/or atresia.
Time frame: 6 months
Population: Two of the five participants analyzed completed the study. Healthy controls did not receive parenteral nutrition and were not analyzed in this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glutamine | Number of Participants With Bloodstream Infections (BSI) | 0 Participants |
| Placebo | Number of Participants With Bloodstream Infections (BSI) | 1 Participants |
Secondary
Head Circumference
Assess the efficacy of 6 months of therapy with enteral Glutamine on head circumference
Time frame: 6 months
Population: The number analyzed at Baseline and days 60, 120 and 180 differ from the overall number analyzed due protocol noncompliance and participant request to withdrawal from the protocol. Healthy controls were not analyzed in this outcome measure because they did not receive parenteral nutrition, L-Glutamine or placebo.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Glutamine | Head Circumference | Head Circumference at Baseline | 42.9 Centimeters |
| Glutamine | Head Circumference | Head Circumference at Day 60 | 43.5 Centimeters |
| Glutamine | Head Circumference | Head Circumference at Day 120 | 48.8 Centimeters |
| Glutamine | Head Circumference | Head Circumference at day 180 | 44.5 Centimeters |
| Placebo | Head Circumference | Head Circumference at day 180 | 46.6 Centimeters |
| Placebo | Head Circumference | Head Circumference at Baseline | 43.8 Centimeters |
| Placebo | Head Circumference | Head Circumference at Day 120 | 46 Centimeters |
| Placebo | Head Circumference | Head Circumference at Day 60 | 43.4 Centimeters |
Secondary
Mid Arm Circumference
Assess the efficacy of 6 months of therapy with enteral Glutamine on mid arm circumference.
Time frame: 6 months
Population: The number analyzed at Baseline and days 60,120 and 180 differ from the overall number analyzed due protocol noncompliance and participant request to withdrawal from the protocol. Healthy controls were not analyzed in this outcome measure because they did not receive parenteral nutrition, L-Glutamine or placebo.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Glutamine | Mid Arm Circumference | Mid Arm Circumference at Baseline | 13 Centimeters |
| Glutamine | Mid Arm Circumference | Mid Arm Circumference at Day 60 | 12.6 Centimeters |
| Glutamine | Mid Arm Circumference | Mid Arm Circumference at Day 120 | 12.5 Centimeters |
| Glutamine | Mid Arm Circumference | Mid Arm Circumference at day 180 | 12.8 Centimeters |
| Placebo | Mid Arm Circumference | Mid Arm Circumference at day 180 | 17.3 Centimeters |
| Placebo | Mid Arm Circumference | Mid Arm Circumference at Baseline | 16.0 Centimeters |
| Placebo | Mid Arm Circumference | Mid Arm Circumference at Day 120 | 8.8 Centimeters |
| Placebo | Mid Arm Circumference | Mid Arm Circumference at Day 60 | 16.0 Centimeters |
Secondary
Weight Velocity
Assess the efficacy of 6 months of therapy with enteral Glutamine on weight velocity.
Time frame: 6 months
Population: The number analyzed at Baseline and days 60, 120 and 180 differ from the overall number analyzed due protocol noncompliance and participant request to withdrawal from the protocol. Healthy controls were not analyzed in this outcome measure because they did not receive parenteral nutrition, L-Glutamine or placebo.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Glutamine | Weight Velocity | Weight at Day 60 | 6.4 Kilograms |
| Glutamine | Weight Velocity | Weight at Baseline | 6.5 Kilograms |
| Glutamine | Weight Velocity | Weight at Day 120 | 7.1 Kilograms |
| Glutamine | Weight Velocity | Weight at day 180 | 7.9 Kilograms |
| Placebo | Weight Velocity | Weight at day 180 | 9.4 Kilograms |
| Placebo | Weight Velocity | Weight at Day 120 | 9.3 Kilograms |
| Placebo | Weight Velocity | Weight at Baseline | 8.1 Kilograms |
| Placebo | Weight Velocity | Weight at Day 60 | 8.4 Kilograms |