Condition category
Pregnancy and Childbirth
Date applied
14/07/2004
Date assigned
09/08/2004
Last edited
04/03/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Willem Fetter

ORCID ID

Contact details

Vrije University Medical Centre
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
+31 (0)20 444 2413
w.fetter@vumc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NTR205

Study information

Scientific title

Acronym

GEEF study

Study hypothesis

Very Low Birth Weight (VLBW) infants may be susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth. Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression. This double-blind randomised controlled trial is designed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity and short-term outcome in VLBW infants. Furthermore, an attempt is made to elucidate the role of glutamine in postnatal adaptation of the gut and modulation of the immune response.

Ethics approval

The National Central Committee on research involving human subjects and the Medical Ethical Review Board of our hospital approved the study protocol.

Study design

Randomised, placebo controlled, parallel group, double blinded trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Very low birth weight infants

Intervention

Enteral glutamine supplementation in a dose of 0.3 g/kg/day between days three and 30 of life versus isonitrogenous placebo supplementation (alanine).

Intervention type

Supplement

Phase

Not Specified

Drug names

Enteral glutamine supplementation

Primary outcome measures

Time to full enteral feeding, defined as a feeding volume greater than or equal to 120 mL/kg/day.

Secondary outcome measures

1. Feeding tolerance:
1.1. Age at finishing parenteral nutrition
1.2. Days of no enteral feeding during study period
1.3. Necrotising enterocolitis
2. Infectious morbidity:
2.1. Serious infections
2.2. Number of infectious episodes
2.3. Cultured micro-organisms
3. Short-term outcomes:
3.1. Weight z scores at birth, day 30 and at discharge
3.2. Patent ductus arteriosus
3.3. Ventilatory support
3.4. Use of oxygen at postmenstrual age of 36 weeks
3.5. Intraventricular hemorrhage
3.6. Retinopathy of prematurity
3.7. Death
3.8. Age at discharge from NICU and at discharge home
4. Intestinal permeability, determined during the 30 day study period
5. Faecal flora, determined during the 30 day study period
6. Plasma Th1/Th2 cytokine concentrations, determined during the 30 day study period
7. Plasma amino acid profiles, determined during the 30 day study period

Overall trial start date

16/09/2001

Overall trial end date

19/10/2004

Reason abandoned

Eligibility

Participant inclusion criteria

1. Infants with a gestational age less than 32 weeks and/or a birth weight less than 1500 g
2. Admitted to the level III Neonatal Intensive Care Unit (NICU) of the Vrije University Medical Centre (VUMC)
3. Written informed consent obtained from all parents

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

107

Participant exclusion criteria

1. Major chromosomal or congenital anomalies
2. Death less than 48 hours after birth
3. Transfer to another hospital less than 48 hours after birth
4. Admission from an extraregional hospital

Recruitment start date

16/09/2001

Recruitment end date

19/10/2004

Locations

Countries of recruitment

Netherlands

Trial participating centre

Vrije University Medical Centre
Amsterdam
1081 HV
Netherlands

Sponsor information

Organisation

Vrije University Medical Centre (VUMC) (The Netherlands)

Sponsor details

De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
+31 (0)20 444 2413
w.fetter@vumc.nl

Sponsor type

Hospital/treatment centre

Website

http://www.vumc.nl/english/

Funders

Funder type

Industry

Funder name

Nutricia Nederland B.V. (The Netherlands) - provided neonatal glutamine and placebo supplementation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Protocol in http://www.ncbi.nlm.nih.gov/pubmed/15341667

Results in:
1. http://www.ncbi.nlm.nih.gov/pubmed/15941893
2. http://www.ncbi.nlm.nih.gov/pubmed/15990633
3. http://www.ncbi.nlm.nih.gov/pubmed/17984413
4. http://www.ncbi.nlm.nih.gov/pubmed/17499398
5. http://www.ncbi.nlm.nih.gov/pubmed/16931609

Publication citations

  1. Protocol

    van den Berg A, van Elburg RM, Twisk JW, Fetter WP, Glutamine-enriched enteral nutrition in very low birth weight infants. Design of a double-blind randomised controlled trial [ISRCTN73254583]., BMC Pediatr, 2004, 4, 17, doi: 10.1186/1471-2431-4-17.

  2. van den Berg A, van Elburg RM, Westerbeek EA, Twisk JW, Fetter WP, Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial., Am. J. Clin. Nutr., 2005, 81, 6, 1397-1404.

  3. van den Berg A, van Elburg RM, Teerlink T, Lafeber HN, Twisk JW, Fetter WP, A randomized controlled trial of enteral glutamine supplementation in very low birth weight infants: plasma amino acid concentrations., J. Pediatr. Gastroenterol. Nutr., 2005, 41, 1, 66-71.

  4. van den Berg A, van Zwol A, Moll HA, Fetter WP, van Elburg RM, Glutamine-enriched enteral nutrition in very low-birth-weight infants: effect on the incidence of allergic and infectious diseases in the first year of life., Arch Pediatr Adolesc Med, 2007, 161, 11, 1095-1101, doi: 10.1001/archpedi.161.11.1095.

  5. van den Berg A, van Elburg RM, Westerbeek EA, van der Linde EG, Knol J, Twisk JW, Fetter WP, The effect of glutamine-enriched enteral nutrition on intestinal microflora in very low birth weight infants: a randomized controlled trial., Clin Nutr, 2007, 26, 4, 430-439, doi: 10.1016/j.clnu.2007.03.002.

  6. van den Berg A, Fetter WP, Westerbeek EA, van der Vegt IM, van der Molen HR, van Elburg RM, The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants: a randomized controlled trial., JPEN J Parenter Enteral Nutr, 30, 5, 408-414.

Additional files

Editorial Notes