Enteral Glutamine in Reducing Bloodstream Infections in Short Bowel Syndrome Infants

• Sponsor: Children's Hospital Medical Center, Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT01576003
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Emmaus Medical, Inc. (Industry), University of Michigan (Other), Emory University (Other), University of Colorado, Denver (Other)
• Enrollment: 10
• Locations: 2
• Arms: 3
• Duration (Months): 38
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bloodstream Infections; Short Bowel Syndrome; Development; Nutrition; Biological Markers	Drug: Glutamine; Dietary Supplement: L-alanine	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy of Enteral Glutamine in Reducing Bloodstream Infections in Short Bowel Syndrome Infants
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glutamine Infants randomized to the Glutamine group will receive L-Glutamine (GLN) administered enterally at a dose of 0.6g/kg body weight/day (0.3g/kg/dose) in 2 divided daily doses for 6 months. GLN will be dissolved in water, breast milk or formula and administered to the subject orally or through their enterostomy tube approximately every 12 hours (twice a day).	Drug: Glutamine; 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months); Other Names: NutreStore
Placebo Comparator: L-alanine Infants randomized to the placebo group will receive L-alanine (ALA) administered enterally at a dose of 0.6g/kg body weight/day in 2 divided doses (0.3g/kg/day twice a day) for 6 months. ALA will be dissolved in water, breast milk or formula and administered to the subject orally or through their enterostomy tube approximately every 12 hours (twice a day).	Dietary Supplement: L-alanine; 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 day (6 months)
No Intervention: Healthy Control Healthy age-matched infants (n=12) will have serial stools collected on 4 occasions, each separated by 60 days.

Outcome Measures

Primary Outcome Measures

1. 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.

2. Length Velocity [6 months]

   Assess the efficacy of 6 months of therapy with enteral Glutamine on length velocity.

Secondary Outcome Measures

1. Head Circumference [6 months]

   Assess the efficacy of 6 months of therapy with enteral Glutamine on head circumference

2. Mid Arm Circumference [6 months]

   Assess the efficacy of 6 months of therapy with enteral Glutamine on mid arm circumference.

3. Weight Velocity [6 months]

   Assess the efficacy of 6 months of therapy with enteral Glutamine on weight velocity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Weeks to 12 Months
• Sexes Eligible for Study: All
• Accepts 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

Exclusion Criteria for Glutamine and Placebo Group of SBS Patients:

• Major congenital or chromosomal anomalies

• Inability to tolerate enteral nutrition that will preclude treatment with enteral Glutamine or L-alanine placebo for > 2 weeks

• Liver/Intestinal transplantation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	C.S. Mott Children's Hosptial	Ann Arbor	Michigan	United States	48109
2	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• Children's Hospital Medical Center, Cincinnati
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Emmaus Medical, Inc.
• University of Michigan
• Emory University
• University of Colorado, Denver

Investigators

• Principal Investigator: Conrad R Cole, MD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 1, 2014

More Information

Publications

None provided.

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT01576003
• Other Study ID Numbers: 2010-2706; 1R21DK088027-01A1
• First Posted: Apr 12, 2012
• Last Update Posted: Jun 11, 2020
• Last Verified: Jun 1, 2020

• Keywords provided by Children's Hospital Medical Center, Cincinnati: Short Bowel Syndrome; Necrotizing Entercolitis (NEC); Atresia; Parenteral Nutrition; Biological Markers; Growth
• Additional relevant MeSH terms: Infections; Communicable Diseases; Sepsis; Short Bowel Syndrome; Syndrome

Study Results

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.

Arm/Group Title	Glutamine	Placebo	Healthy Control
Arm/Group Description	L-Glutamine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)	L-alanine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 day (6 months)	No Intervention - Healthy age-matched infants provided stools on 4 occasions, each separated by 60 days.
Period Title: Overall Study
STARTED	2	3	4
COMPLETED	1	1	4
NOT COMPLETED	1	2	0

Baseline Characteristics

Arm/Group Title	Glutamine	Placebo	Healthy Control	Total
Arm/Group Description	L-Glutamine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)	L-Alanine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)	No Intervention - Healthy age-matched infants provided stools on 4 occasions, each separated by 60 days.	Total of all reporting groups
Overall Participants	2	3	4	9
Age, Customized (Count of Participants)
6 weeks through 2 months	0 0%	0 0%	1 25%	1 11.1%
3 months through 4 months	0 0%	1 33.3%	1 25%	2 22.2%
5 months through 6 months	1 50%	0 0%	1 25%	2 22.2%
7 months through 8 months	1 50%	0 0%	1 25%	2 22.2%
9 months through 10 months	0 0%	2 66.7%	0 0%	2 22.2%
11 months through 12 months	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%	2 66.7%	0 0%	3 33.3%
Male	1 50%	1 33.3%	4 100%	6 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	3 100%	4 100%	9 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Cause of Short Bowel Resection (Count of Participants)
Atresia	1 50%	1 33.3%	0 0%	2 22.2%
Necrotizing enterocolitis (NEC)	1 50%	0 0%	0 0%	1 11.1%
NEC and Atresia	0 0%	2 66.7%	0 0%	2 22.2%
Birth Weight (kilograms) [Mean (Full Range) ]
Mean (Full Range) [kilograms]	2.4	2.6	2.35
Bowel Length (Centimeters) [Mean (Full Range) ]
Mean (Full Range) [Centimeters]	49.5	82.0	69.0

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Bloodstream Infections (BSI)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Glutamine	Placebo
Arm/Group Description	Glutamine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)	L-alanine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 day (6 months)
Measure Participants	2	3
Count of Participants [Participants]	0 0%	1 33.3%

2. Primary Outcome

Title	Length Velocity
Description	Assess the efficacy of 6 months of therapy with enteral Glutamine on length velocity.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

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/Group Title	Glutamine	Placebo
Arm/Group Description	L-Glutamine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)	L-alanine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 day (6 months)
Measure Participants	2	3
Length at Baseline	60.9	66.0
Length at Day 60	62.2	67.5
Length at Day 120	66.8	73.7
Length at Day 180	68	78.2

3. Secondary Outcome

Title	Head Circumference
Description	Assess the efficacy of 6 months of therapy with enteral Glutamine on head circumference
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

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/Group Title	Glutamine	Placebo
Arm/Group Description	L-Glutamine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)	L-alanine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 day (6 months)
Measure Participants	2	3
Head Circumference at Baseline	42.9	43.8
Head Circumference at Day 60	43.5	43.4
Head Circumference at Day 120	48.8	46
Head Circumference at day 180	44.5	46.6

4. Secondary Outcome

Title	Mid Arm Circumference
Description	Assess the efficacy of 6 months of therapy with enteral Glutamine on mid arm circumference.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

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/Group Title	Glutamine	Placebo
Arm/Group Description	L-Glutamine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)	L-alanine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 day (6 months)
Measure Participants	2	3
Mid Arm Circumference at Baseline	13	16.0
Mid Arm Circumference at Day 60	12.6	16.0
Mid Arm Circumference at Day 120	12.5	8.8
Mid Arm Circumference at day 180	12.8	17.3

5. Secondary Outcome

Title	Weight Velocity
Description	Assess the efficacy of 6 months of therapy with enteral Glutamine on weight velocity.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

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/Group Title	Glutamine	Placebo
Arm/Group Description	L-Glutamine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)	L-alanine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 day (6 months)
Measure Participants	2	3
Weight at Baseline	6.5	8.1
Weight at Day 60	6.4	8.4
Weight at Day 120	7.1	9.3
Weight at day 180	7.9	9.4

Adverse Events

Time Frame	6 months
Arm/Group Title	Glutamine		Placebo		Healthy Control
Arm/Group Description	L-Glutamine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)		L-alanine: 0.3 g/kg, taken orally/feeding tube every 12 hours/twice a day for 180 days (6 months)		No Intervention - Healthy age-matched infants provided stools on 4 occasions, each separated by 60 days.
All Cause Mortality
	Glutamine		Placebo		Healthy Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)		0/4 (0%)
Serious Adverse Events
	Glutamine		Placebo		Healthy Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		2/3 (66.7%)		0/4 (0%)
Blood and lymphatic system disorders
Sepsis	0/2 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
Infections and infestations
Viral Illness	0/2 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
Hospitalization for fever in a patient with a central line	1/2 (50%)	1	1/3 (33.3%)	1	0/4 (0%)	0
Respiratory syncytial virus (RSV)	0/2 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	Glutamine		Placebo		Healthy Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		3/3 (100%)		0/4 (0%)
Ear and labyrinth disorders
Otitis Media	0/2 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
Gastrointestinal disorders
Diarrhea	1/2 (50%)	1	0/3 (0%)	0	0/4 (0%)	0
Flatulence	0/2 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
General disorders
Vomiting	0/2 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0
Central Venous Catheter (CVC) dislodged	1/2 (50%)	1	0/3 (0%)	0	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Diaper Dermatitis	0/2 (0%)	0	2/3 (66.7%)	2	0/4 (0%)	0
Rash Maculopapular	1/2 (50%)	1	0/3 (0%)	0	0/4 (0%)	0

Limitations/Caveats

Recruitment was low due to the improvement in care from the use of ethanol lock therapy and improved techniques related to line care. Early termination of participants lead to small number of subjects analyzed and inability to analyze all study aims.

More Information

Certain Agreements

All Principal Investigators ARE 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.