Clinical trial NCT02509728: Metabolic Effects of Choline and Docosahexaenoic Acid Supplementation in Preterm Infants
Official title: Nahrungsergänzung Mit Cholin- Und Docosahexaensäure Bei Sehr Unreifen Frühgeborenen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infant, Premature
Keywords: choline
docosahexaenoic acid
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2015-07-28
Enrollment: 24
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: plasma concentrations of choline
timeFrame: following 7 days of supplementation
Secondary outcomes:
measure: de-novo DHA-phosphatidylcholine synthesis
timeFrame: following 7 days of supplementation at 12hours after D9-choline administration
measure: DHA-phosphatidylcholine turnover
timeFrame: following 7.5 days of supplementation, from 12hours to 60 hours after D9-choline administration
measure: fractions and concentrations of molecular species of phosphatidylcholine
timeFrame: baseline and following 7.5 and 10 days of supplementation
measure: plasma concentrations of choline
timeFrame: baseline and following 7.5 and 10 days of supplementation
measure: Plasma concentrations of betaine (a metabolite of choline)
timeFrame: baseline and following 7.5 and 10 days of supplementation
measure: Plasma concentrations of dimethylglycine (a metabolite of choline)
timeFrame: baseline and following 7.5 and 10 days of supplementation
measure: Plasma concentrations of trimethylamineoxide (TMAO, a metabolite of choline)
timeFrame: baseline and following 7.5 and 10 days of supplementation
Other outcomes:
Locations:
city: Tuebingen
country: Germany
facility: University Hospital of Tuebingen
Study officials:
affiliation: University Hospital Tuebingen
name: Axel Franz, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
citation: Bernhard W, Bockmann K, Maas C, Mathes M, Hovelmann J, Shunova A, Hund V, Schleicher E, Poets CF, Franz AR. Combined choline and DHA supplementation: a randomized controlled trial. Eur J Nutr. 2020 Mar;59(2):729-739. doi: 10.1007/s00394-019-01940-7. Epub 2019 Mar 11.