Infant, NewbornPhase 3GlutamineNCT00005775
Glutamine Supplementation to Prevent Death or Infection in Extremely Premature Infants
A Phase 3 study testing Glutamine in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 15 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 72 hours
- Conditions the study is for
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age
- What is being tested?
- Glutamine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,433 participants
- Where
- 15 sitesUnited States
- Study dates
- Jul 1999to Aug 2001
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 72 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 401-1000 gm
- More than 12 hrs and less than 72 hrs after birth; intravenous access
- Parental consent
Who cannot join
- One or more major congenital anomalies
- Infants meeting criteria for terminal illness
- Congenital nonbacterial infection with overt signs at birth
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
RTI International
Durham, North Carolina, 27705
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Miami
Miami, Florida, 33136
Yale University
New Haven, Connecticut, 06504
Stanford University
Palo Alto, California, 94304
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of California at San Diego
San Diego, California, 92103-8774
About this study
Official title: Randomized Controlled Trial of Parenteral Glutamine Supplementation for Extremely-Low-Birth-Weight (ELBW) Infants
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.
Read the detailed description
Meeting the protein and energy requirements of extremely premature infants in early postnatal life requires early hyperalimentation and the gradual introduction of enteral feedings. Glutamine, which is the most abundant amino acid in the human body and taken up in greatest quantity by the fetus from the placenta, is not routinely provided in neonatal parenteral nutrition preparations.
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.
Infants received a neurodevelopmental assessment by masked, certified examiners at 18-22 months postmenstrual age.
- Conditions
- Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Sepsis
- Being tested
- Glutamine, Placebo
- Keywords
- NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW) infants, Prematurity, Glutamine, Total parenteral nutrition, Nutrition, Very low birth weight (VLBW) infants
- Medical subject headings
- Premature Birth, Sepsis, Hyperphagia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlutamineDrug
Also called L-Glutamine, TrophAmine
Infants randomized to glutamine supplementation will receive glutamine any time that parenteral nutrition is required during the first 120 days of hospitalization.
PlaceboDrug
Also called TrophAmine
TrophAmine given any time that parenteral nutrition is required during the first 120 days of hospitalization.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Glutamine |
| Placebo | Placebo comparator | Standard TrophAmine (B. Braun/McGaw) with cysteine hydrochloride (40mg/gm amino acids) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death or late-onset sepsis
Measured: 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
Measured: At hospital discharge
Necrotizing Enterocolitis
Measured: At hospital discharge
Episodes of late-onset sepsis
Measured: At hospital discharge
Growth (days to reach 1500 grams)
Measured: At hospital discharge
Number of days on parenteral nutrition
Measured: At hospital discharge
Length of stay in NICU
Measured: At hospital discharge
Neurodevelopmental outcome
Measured: 18-22 months corrrected age
Levels of pro-inflammatory cytokines
Measured: In the perinatal period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2000 (estimated)
- Study startJul 1999
- Primary completionDec 2000
- Study completionAug 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Infant, NewbornStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,433 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- National Center for Research Resources (NCRR)
- Investigators
- Brenda B. Poindexter, MD MS, Principal investigator, Indiana UniversityWaldemar A. Carlo, MD, Principal investigator, University of Alabama at BirminghamNeil N. Finer, MD, Principal investigator, University of California, San DiegoAvroy A. Fanaroff, MD, Principal investigator, Case Western Reserve UniversityEdward F. Donovan, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiBarbara J. Stoll, MD, Principal investigator, Emory UniversityCharles R. Bauer, MD, Principal investigator, University of MiamiLu-Ann Papile, MD, Principal investigator, University of New Mexico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005775
- Sponsor's protocol ID
- NICHD-NRN-0020
- Other IDs
- U10HD027856, U10HD021364, U10HD034216, U10HD034167, U10HD021397, U10HD027853, U10HD027871, U10HD021415
- Acronym
- Glutamine
- Status last verified
- Jun 2015
- First submitted
- 1 Jun 2000
- Last updated
- 8 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 12600870Poindexter 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.
PubMed 15121931Oh 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.
PubMed 16356432Poindexter 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.
PubMed 16615955Vohr 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.
PubMed 16818526Vohr 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.
PubMed 17908750Meinzen-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.
PubMed 18716628Peralta-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.
PubMed 19403482Amari 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.
PubMed 33006765
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Parenteral Glutamine Supplementation for Extremely-Low-Birth-Weight (ELBW) Infants
- ClinicalTrials.gov ID
- NCT00005775
- Acronym / sponsor ID
- Glutamine / NICHD-NRN-0020
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,433 participants (actual)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- National Center for Research Resources (NCRR)
- Study start
- Jul 1999
- Primary completion
- Dec 2000 (actual)
- Study completion
- Aug 2001 (actual)
- First posted
- 2 Jun 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Meeting the protein and energy requirements of extremely premature infants in early postnatal life requires early hyperalimentation and the gradual introduction of enteral feedings. Glutamine, which is the most abundant amino acid in the human body and taken up in greatest quantity by the fetus from the placenta, is not routinely provided in neonatal parenteral nutrition preparations.
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.
Infants received a neurodevelopmental assessment by masked, certified examiners at 18-22 months postmenstrual age.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glutamine | Experimental | Drug: GlutamineTrophAmine (B. Braun/McGaw) with cysteine hydrochloride (40mg/gm amino acids) with L-glutamine added (20% of the total amount of amino acids) |
| Placebo | Placebo comparator | Drug: PlaceboStandard TrophAmine (B. Braun/McGaw) with cysteine hydrochloride (40mg/gm amino acids) |
Who may qualify
- Ages
- Up to 72 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 401-1000 gm
- More than 12 hrs and less than 72 hrs after birth; intravenous access
- Parental consent
Key exclusion criteria (3 listed)
- One or more major congenital anomalies
- Infants meeting criteria for terminal illness
- Congenital nonbacterial infection with overt signs at birth
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlutamineAlso: L-Glutamine, TrophAmineInfants randomized to glutamine supplementation will receive glutamine any time that parenteral nutrition is required during the first 120 days of hospitalization. | Drug | Glutamine |
| PlaceboAlso: TrophAmineTrophAmine given any time that parenteral nutrition is required during the first 120 days of hospitalization. | Drug | Placebo |
Primary outcome
Death or late-onset sepsis
Time frame: At hospital discharge
8 secondary outcomes
Tolerance of enteral feeding (number of days to reach full enteral feeds) and decrease number of episodes of feeding intolerance
Time frame: At hospital discharge
Necrotizing Enterocolitis
Time frame: At hospital discharge
Episodes of late-onset sepsis
Time frame: At hospital discharge
Growth (days to reach 1500 grams)
Time frame: At hospital discharge
Number of days on parenteral nutrition
Time frame: At hospital discharge
Length of stay in NICU
Time frame: At hospital discharge
Neurodevelopmental outcome
Time frame: 18-22 months corrrected age
Levels of pro-inflammatory cytokines
Time frame: In the perinatal period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.
- Results publication: PubMed 12600870Poindexter 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.
- Results publication: PubMed 15121931Poindexter 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.
- Results publication: PubMed 16356432Oh 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.
- Results publication: PubMed 16615955Poindexter 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.
- Results publication: PubMed 16818526Vohr 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.
- Results publication: PubMed 17908750Vohr 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.
- Results publication: PubMed 18716628Meinzen-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.
- Results publication: PubMed 19403482Peralta-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.
- Derived from this study: PubMed 33006765Amari 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.
- NICHD Neonatal Research NetworkLink provided by the sponsor.
- Click here for the Cochrane review "Glutamine supplementation for preventionof morbidity in the preterm infant."Link provided by the sponsor.
- NICHD Pregnancy \& Perinatology BranchLink provided by the sponsor.
Related trials for Infant, Newborn
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
RecruitingObservational study
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
Fanconi Anemia, Inherited Bone Marrow Failure Syndrome
Active, not recruitingPhase 1
A Study of the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of BCX17725
Netherton Syndrome
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brenda B. Poindexter, MD MS principal investigator
Indiana University
Waldemar A. Carlo, MD principal investigator
University of Alabama at Birmingham
Neil N. Finer, MD principal investigator
University of California, San Diego
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Glutamine in people with Infant, Newborn and Infant, Low Birth Weight, run by NICHD Neonatal Research Network at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Death or late-onset sepsis (time frame: At hospital discharge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005775, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2015.