Infant, PrematureNCT02509728
Metabolic Effects of Choline and Docosahexaenoic Acid Supplementation in Preterm Infants
A study testing choline supplementation, DHA supplementation and standard nutrition in people with Infant, Premature, run by University Hospital Tuebingen at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 1 week to 2 months
- Conditions the study is for
- Infant, Premature
- What is being tested?
- choline supplementation, DHA supplementation and standard nutrition
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2015to 31 Dec 2017
- Phase
- Interventional
- 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 1 week to 2 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- preterm infants with a gestational age at birth between 24 and 32 weeks
- on almost complete enteral feeding (>75% of total fluid intake)
Who cannot join
- insufficient enteral intake,
- gastrointestinal disease,
- missing parental consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Nahrungsergänzung Mit Cholin- Und Docosahexaensäure Bei Sehr Unreifen Frühgeborenen
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.
Read the 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.
- Conditions
- Infant, Premature
- Being tested
- choline supplementation, DHA supplementation, standard nutrition
- Keywords
- choline, docosahexaenoic acid
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
choline supplementationDietary supplement
in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days
DHA supplementationDietary supplement
in addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days
standard nutritionDietary supplement
standard nutrition
| Study group | Role | What they receive |
|---|---|---|
| standard nutrition | Active comparator | standard nutrition Receives: Dietary Supplement: standard nutrition |
| choline supplementation | Experimental | in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days Receives: Dietary Supplement: choline supplementation; Dietary Supplement: standard nutrition |
| DHA supplementation | Experimental | in addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days Receives: Dietary Supplement: DHA supplementation; Dietary Supplement: standard nutrition |
| choline and DHA supplementation | Experimental | in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride and 60mg/kg of DHA for 10 days Receives: Dietary Supplement: choline supplementation; Dietary Supplement: DHA supplementation; Dietary Supplement: standard nutrition |
What is being measured
The primary outcome is the main question the study is designed to answer.
plasma concentrations of choline
Measured: following 7 days of supplementation
Secondary outcomes (7)
de-novo DHA-phosphatidylcholine synthesis
Measured: following 7 days of supplementation at 12hours after D9-choline administration
DHA-phosphatidylcholine turnover
Measured: following 7.5 days of supplementation, from 12hours to 60 hours after D9-choline administration
fractions and concentrations of molecular species of phosphatidylcholine
Measured: baseline and following 7.5 and 10 days of supplementation
plasma concentrations of choline
Measured: baseline and following 7.5 and 10 days of supplementation
Plasma concentrations of betaine (a metabolite of choline)
Measured: baseline and following 7.5 and 10 days of supplementation
Plasma concentrations of dimethylglycine (a metabolite of choline)
Measured: baseline and following 7.5 and 10 days of supplementation
Plasma concentrations of trimethylamineoxide (TMAO, a metabolite of choline)
Measured: baseline and following 7.5 and 10 days of supplementation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2015 (estimated)
- Study startJul 2015
- Primary completion31 Oct 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Infant, PrematureStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Axel Franz, MD, Principal investigator, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02509728
- Sponsor's protocol ID
- Choline and DHA for Preemies 2
- Status last verified
- May 2018
- First submitted
- 22 Jul 2015
- Last updated
- 15 May 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25148882Bernhard 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.
PubMed 24464176Bernhard 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.
PubMed 22961562Bernhard 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.
PubMed 30859363
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nahrungsergänzung Mit Cholin- Und Docosahexaensäure Bei Sehr Unreifen Frühgeborenen
- ClinicalTrials.gov ID
- NCT02509728
- Acronym / sponsor ID
- Choline and DHA for Preemies 2
- Conditions
- Infant, Premature
- Keywords
- choline, docosahexaenoic acid
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- Jul 2015 (actual)
- Primary completion
- 31 Oct 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 28 Jul 2015 (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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| standard nutrition | Active comparator | Dietary Supplement: standard nutritionstandard nutrition |
| choline supplementation | Experimental | Dietary Supplement: choline supplementation, Dietary Supplement: standard nutritionin addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days |
| DHA supplementation | Experimental | Dietary Supplement: DHA supplementation, Dietary Supplement: standard nutritionin addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days |
| choline and DHA supplementation | Experimental | Dietary Supplement: choline supplementation, Dietary Supplement: DHA supplementation, Dietary Supplement: standard nutritionin addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride and 60mg/kg of DHA for 10 days |
Who may qualify
- Ages
- 1 week to 2 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- preterm infants with a gestational age at birth between 24 and 32 weeks
- on almost complete enteral feeding (>75% of total fluid intake)
Key exclusion criteria (3 listed)
- insufficient enteral intake,
- gastrointestinal disease,
- missing parental consent
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 |
|---|---|---|
| choline supplementationin addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days | Dietary supplement | choline and DHA supplementation, choline supplementation |
| DHA supplementationin addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days | Dietary supplement | DHA supplementation, choline and DHA supplementation |
| standard nutritionstandard nutrition | Dietary supplement | DHA supplementation, choline and DHA supplementation, choline supplementation, standard nutrition |
Primary outcome
plasma concentrations of choline
Time frame: following 7 days of supplementation
7 secondary outcomes
de-novo DHA-phosphatidylcholine synthesis
Time frame: following 7 days of supplementation at 12hours after D9-choline administration
DHA-phosphatidylcholine turnover
Time frame: following 7.5 days of supplementation, from 12hours to 60 hours after D9-choline administration
fractions and concentrations of molecular species of phosphatidylcholine
Time frame: baseline and following 7.5 and 10 days of supplementation
plasma concentrations of choline
Time frame: baseline and following 7.5 and 10 days of supplementation
Plasma concentrations of betaine (a metabolite of choline)
Time frame: baseline and following 7.5 and 10 days of supplementation
Plasma concentrations of dimethylglycine (a metabolite of choline)
Time frame: baseline and following 7.5 and 10 days of supplementation
Plasma concentrations of trimethylamineoxide (TMAO, a metabolite of choline)
Time frame: baseline and following 7.5 and 10 days of supplementation
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 15 May 2018.
- Background: PubMed 25148882Bernhard 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.
- Background: PubMed 24464176Bernhard 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.
- Background: PubMed 22961562Bernhard 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.
- Derived from this study: PubMed 30859363Bernhard 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.
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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.
Axel Franz, MD principal investigator
University Hospital Tuebingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing choline supplementation, DHA supplementation and standard nutrition in people with Infant, Premature, run by University Hospital Tuebingen at 1 site in Germany.
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 2 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 15 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
plasma concentrations of choline (time frame: following 7 days of supplementation). 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 NCT02509728, which also lists 4 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 15 May 2018.