Glutamine Supplementation to Prevent Death or Infection in Extremely Premature Infants

NCT00005775 | Completed Phase 3 DMC

• 22 other identifiers: NICHD-NRN-0020U10HD027856U10HD021364U10HD034216U10HD034167U10HD021397U10HD027853U10HD027871U10HD021415U10HD027904U10HD027881U10HD021385U10HD027851U10HD027880U10HD021373U01HD036790M01RR008084M01RR006022M01RR000750M01RR000997M01RR000070M01RR001032
• Study Type: interventional
• Target: 1,433
• Locations: 1 country
• Sites: 15

Brief Summary

This large multicenter double-masked clinical trial tested whether supplementation of standard neonatal parenteral nutrition with glutamine would reduce the risk of death or late-onset sepsis in extremely-low-birth-weight (ELBW, less than or equal to 1000 gm) infants. Neonates with birth weights of 401-1000gm were randomized to standard TrophAmine or TrophAmine supplemented with glutamine before 72 hours and continued until the infants are tolerating full enteral feedings.

Conditions

Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature; Sepsis

Keywords

NICHD Neonatal Research Network; Extremely Low Birth Weight (ELBW) infants; Prematurity; Glutamine; Total parenteral nutrition; Nutrition; Very low birth weight (VLBW) infants

Outcome Measures

Primary Outcomes (1)

• Death or late-onset sepsis

  At hospital discharge

Secondary Outcomes (8)

• Tolerance of enteral feeding (number of days to reach full enteral feeds) and decrease number of episodes of feeding intolerance

  At hospital discharge

• Necrotizing Enterocolitis

  At hospital discharge

• Episodes of late-onset sepsis

  At hospital discharge

• Growth (days to reach 1500 grams)

  At hospital discharge

• Number of days on parenteral nutrition

  At hospital discharge

Study Arms (2)

Glutamine

EXPERIMENTAL

TrophAmine (B. Braun/McGaw) with cysteine hydrochloride (40mg/gm amino acids) with L-glutamine added (20% of the total amount of amino acids)

Drug: Glutamine

Placebo

PLACEBO COMPARATOR

Standard TrophAmine (B. Braun/McGaw) with cysteine hydrochloride (40mg/gm amino acids)

Drug: Placebo

Interventions

Glutamine DRUG

Infants randomized to glutamine supplementation will receive glutamine any time that parenteral nutrition is required during the first 120 days of hospitalization.

Also known as: L-Glutamine, TrophAmine

Glutamine

Placebo DRUG

TrophAmine given any time that parenteral nutrition is required during the first 120 days of hospitalization.

Also known as: TrophAmine

Placebo

Eligibility Criteria

• Age: Up to 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• More than 12 hrs and less than 72 hrs after birth; intravenous access
• Parental consent

You may not qualify if:

• One or more major congenital anomalies
• Infants meeting criteria for terminal illness
• Congenital nonbacterial infection with overt signs at birth

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Center for Research Resources (NCRR): collaborator

Study Sites (15)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of California at San Diego

San Diego, California, 92103-8774, United States

Location

Yale University

New Haven, Connecticut, 06504, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (9)

• Poindexter BB, Ehrenkranz RA, Stoll BJ, Koch MA, Wright LL, Oh W, Papile LA, Bauer CR, Carlo WA, Donovan EF, Fanaroff AA, Korones SB, Laptook AR, Shankaran S, Stevenson DK, Tyson JE, Lemons JA; National Institute of Child Health and Human Development Neonatal Research Network. Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants. Am J Clin Nutr. 2003 Mar;77(3):737-43. doi: 10.1093/ajcn/77.3.737.

  PMID: 12600870 RESULT

• Poindexter BB, Ehrenkranz RA, Stoll BJ, Wright LL, Poole WK, Oh W, Bauer CR, Papile LA, Tyson JE, Carlo WA, Laptook AR, Narendran V, Stevenson DK, Fanaroff AA, Korones SB, Shankaran S, Finer NN, Lemons JA; National Institute of Child Health and Human Development Neonatal Research Network. Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants. Pediatrics. 2004 May;113(5):1209-15. doi: 10.1542/peds.113.5.1209.

  PMID: 15121931 RESULT

• Oh W, Poindexter BB, Perritt R, Lemons JA, Bauer CR, Ehrenkranz RA, Stoll BJ, Poole K, Wright LL; Neonatal Research Network. Association between fluid intake and weight loss during the first ten days of life and risk of bronchopulmonary dysplasia in extremely low birth weight infants. J Pediatr. 2005 Dec;147(6):786-90. doi: 10.1016/j.jpeds.2005.06.039.

  PMID: 16356432 RESULT

• Poindexter BB, Langer JC, Dusick AM, Ehrenkranz RA; National Institute of Child Health and Human Development Neonatal Research Network. Early provision of parenteral amino acids in extremely low birth weight infants: relation to growth and neurodevelopmental outcome. J Pediatr. 2006 Mar;148(3):300-305. doi: 10.1016/j.jpeds.2005.10.038.

  PMID: 16615955 RESULT

• Vohr BR, Poindexter BB, Dusick AM, McKinley LT, Wright LL, Langer JC, Poole WK; NICHD Neonatal Research Network. Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics. 2006 Jul;118(1):e115-23. doi: 10.1542/peds.2005-2382.

  PMID: 16818526 RESULT

• Vohr BR, Poindexter BB, Dusick AM, McKinley LT, Higgins RD, Langer JC, Poole WK; National Institute of Child Health and Human Development National Research Network. Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age. Pediatrics. 2007 Oct;120(4):e953-9. doi: 10.1542/peds.2006-3227.

  PMID: 17908750 RESULT

• Meinzen-Derr J, Poindexter B, Wrage L, Morrow AL, Stoll B, Donovan EF. Role of human milk in extremely low birth weight infants' risk of necrotizing enterocolitis or death. J Perinatol. 2009 Jan;29(1):57-62. doi: 10.1038/jp.2008.117. Epub 2008 Aug 21.

  PMID: 18716628 RESULT

• Peralta-Carcelen M, Moses M, Adams-Chapman I, Gantz M, Vohr BR; NICHD Neonatal Research Network; National Institutes of Health. Stability of neuromotor outcomes at 18 and 30 months of age after extremely low birth weight status. Pediatrics. 2009 May;123(5):e887-95. doi: 10.1542/peds.2008-0135.

  PMID: 19403482 RESULT

• Amari S, Shahrook S, Namba F, Ota E, Mori R. Branched-chain amino acid supplementation for improving growth and development in term and preterm neonates. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD012273. doi: 10.1002/14651858.CD012273.pub2.

  PMID: 33006765 DERIVED

Related Links

• NICHD Neonatal Research Network
• Click here for the Cochrane review "Glutamine supplementation for preventionof morbidity in the preterm infant."
• NICHD Pregnancy \& Perinatology Branch

MeSH Terms

Conditions

Premature Birth; Sepsis; Hyperphagia

Interventions

Glutamine; amino-acid, glucose, and electrolyte solution

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral

Study Officials

• Brenda B. Poindexter, MD MS

  Indiana University

  PRINCIPAL INVESTIGATOR

• Waldemar A. Carlo, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Neil N. Finer, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Avroy A. Fanaroff, MD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

• Edward F. Donovan, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Barbara J. Stoll, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Charles R. Bauer, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Lu-Ann Papile, MD

  University of New Mexico

  PRINCIPAL INVESTIGATOR

• W. Kenneth Poole, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

• David K. Stevenson, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Sheldon B. Korones, MD

  University of Tennessee

  PRINCIPAL INVESTIGATOR

• Jon E. Tyson, MD MPH

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

• Abbot R. Laptook, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• Seetha Shankaran, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• William Oh, MD

  Women and Infants Hospital, Brown University

  PRINCIPAL INVESTIGATOR

• Richard A. Ehrenkranz, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: June 1, 2000
• First Posted: June 2, 2000
• Study Start: July 1, 1999
• Primary Completion: December 1, 2000
• Study Completion: August 1, 2001
• Last Updated: June 8, 2015

Record last verified: 2015-06

Locations

US (15)