Metabolic Effects of Choline and Docosahexaenoic Acid Supplementation in Preterm Infants

Not Applicable

Completed

• Conditions: Infant, Premature
• Interventions: Dietary Supplement: DHA supplementation; Dietary Supplement: choline supplementation; Dietary Supplement: standard nutrition

• Registration Number: NCT02509728
• Lead Sponsor: University Hospital Tuebingen

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2015-07-22
• Study First Submitted QC: 2015-07-27
• Study First Posted: 2015-07-28
• Primary Completion: 2017-10-31
• Study Completion: 2017-12-31
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-09
• Last Update Posted: 2018-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
choline supplementation	standard nutrition	in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days
DHA supplementation	DHA supplementation	in addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days
choline and DHA supplementation	DHA supplementation	in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride and 60mg/kg of DHA for 10 days
DHA supplementation	standard nutrition	in addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days
choline supplementation	choline supplementation	in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days
choline and DHA supplementation	choline supplementation	in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride and 60mg/kg of DHA for 10 days
standard nutrition	standard nutrition	standard nutrition
choline and DHA supplementation	standard nutrition	in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride and 60mg/kg of DHA for 10 days

Primary Outcome Measures

Name	Time	Method
plasma concentrations of choline	following 7 days of supplementation

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University Hospital of Tuebingen; 🇩🇪 Tuebingen, Germany