Metabolic Effects of Choline and Docosahexaenoic Acid Supplementation in Preterm Infants

Infant, Premature Clinical Trial

Official title:

Nahrungsergänzung Mit Cholin- Und Docosahexaensäure Bei Sehr Unreifen Frühgeborenen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02509728
• Other study ID #: Choline and DHA for Preemies 2
• Status: Completed
• Phase: N/A
• Start date: July 2015
• Est. completion date: December 31, 2017

Study information

• Verified date: May 2018
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To explore the effects of enteral choline and DHA supplementation on plasma choline and DHA-PC concentrations and metabolism, this randomized controlled study will assign 40 preterm infants to 1 of 4 groups: standard care, choline supplementation, DHA supplementation, and choline and DHA supplementation.

After 7 days of supplementation, a single dose of stable isotope labelled choline will be administered and the kinetics of newly synthesized DHA-PC determined to assess plasma levels, uptake and distribution of choline and DHA.

This study is designed to inform larger studies evaluating this approach of enteral co-application of choline and DHA on clinical important outcomes.

Description:

In utero, there is a constant high supply of choline to the fetus. Preterm delivery disrupts this maternal-fetal choline-transfer. We have shown that choline plasma levels rapidly half after preterm delivery. We also demonstrated that plasma DHA-PC rapidly falls after preterm delivery. DHA supplementation has been evaluated and found safe, however the clinical benefits have been smaller than expected. We speculate that choline deficiency may have contributed to the smaller than expected benefit of DHA supplementation in the past.

This study verifies the hypothesis that concomitant supply of choline and DHA will improve DHA-PC availability and turn-over. This is important because DHA-PC is the transport molecule for the DHA transport to the brain and the retina.

To explore the effects of enteral choline and DHA supplementation on plasma choline and DHA-PC concentrations, this randomized controlled study will assign 40 preterm infants to 1 of 4 groups: standard care, choline supplementation, DHA supplementation, and choline and DHA supplementation.

After 7 days of supplementation, a single dose of stable isotope labelled choline will be administered and the kinetics of newly synthesized DHA-PC determined to assess plasma levels, uptake and distribution of choline and DHA.

This study is designed to inform future larger studies evaluating this approach of enteral co-application of choline and DHA on important clinical outcomes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 31, 2017
• Est. primary completion date: October 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Months

Eligibility

Inclusion Criteria:

• preterm infants with a gestational age at birth between 24 and 32 weeks

• on almost complete enteral feeding (>75% of total fluid intake)

Exclusion Criteria:

• insufficient enteral intake,

• gastrointestinal disease,

• missing parental consent

Related Conditions & MeSH terms

• Infant, Premature

Intervention

Dietary Supplement:
• choline supplementation
in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days
• DHA supplementation
in addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days
• standard nutrition
standard nutrition

Locations

Country	Name	City	State
Germany	University Hospital of Tuebingen	Tuebingen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

References & Publications (3)

Bernhard W, Full A, Arand J, Maas C, Poets CF, Franz AR. Choline supply of preterm infants: assessment of dietary intake and pathophysiological considerations. Eur J Nutr. 2013 Apr;52(3):1269-78. doi: 10.1007/s00394-012-0438-x. Epub 2012 Sep 9. — View Citation

Bernhard W, Raith M, Koch V, Kunze R, Maas C, Abele H, Poets CF, Franz AR. Plasma phospholipids indicate impaired fatty acid homeostasis in preterm infants. Eur J Nutr. 2014 Oct;53(7):1533-47. doi: 10.1007/s00394-014-0658-3. Epub 2014 Jan 24. — View Citation

Bernhard W, Raith M, Kunze R, Koch V, Heni M, Maas C, Abele H, Poets CF, Franz AR. Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma. Eur J Nutr. 2015 Aug;54(5):733-41. doi: 10.1007/s00394-014-0751-7. Epub 2014 Aug 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	plasma concentrations of choline		following 7 days of supplementation
Secondary	de-novo DHA-phosphatidylcholine synthesis		following 7 days of supplementation at 12hours after D9-choline administration
Secondary	DHA-phosphatidylcholine turnover		following 7.5 days of supplementation, from 12hours to 60 hours after D9-choline administration
Secondary	fractions and concentrations of molecular species of phosphatidylcholine		baseline and following 7.5 and 10 days of supplementation
Secondary	plasma concentrations of choline		baseline and following 7.5 and 10 days of supplementation
Secondary	Plasma concentrations of betaine (a metabolite of choline)		baseline and following 7.5 and 10 days of supplementation
Secondary	Plasma concentrations of dimethylglycine (a metabolite of choline)		baseline and following 7.5 and 10 days of supplementation
Secondary	Plasma concentrations of trimethylamineoxide (TMAO, a metabolite of choline)		baseline and following 7.5 and 10 days of supplementation