Synergy Between Choline and DHA

January 15, 2020 updated by: Cornell University

Maternal Choline Supplementation and Its Impact on Docosahexaenoic Acid Supply in Human Pregnancy

The purpose of this study is to determine whether choline supplementation influences the availability of docosahexaenoic acid throughout pregnancy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Metabolic synergy exists between choline, phospholipid, and polyunsaturated fatty acid metabolism. Previous evidence from our laboratory has shown that higher dietary choline intakes increase the amount of docosahexaenoic acid (DHA) incorporated into phosphatidylcholine (PC), as measured by PC-DHA concentrations in circulating erythrocytes. PC-DHA results from the production of PC through the phosphatidyl N-ethanolamine methyltransferase (PEMT) pathway and is critical for exporting fat from the liver to peripheral tissues. We are expanding this work to pregnant women, for whom DHA intake is critical to support the developing infant's growth, by undertaking a double blind, randomized controlled trial of choline supplementation (500mg) throughout the 2nd and 3rd trimesters of pregnancy. All women will consume 200mg of docosahexaenoic acid (DHA), a prenatal vitamin, and 25-50mg of deuterated choline (choline d9) daily throughout the duration of the trial. The use of a stable isotope will allow for modeling of choline dynamics throughout the 2nd and 3rd trimester of pregnancy, and calculate the activity of PEMT in pregnant women. Consenting participants will provide a baseline blood draw, followed by 2 additional blood draws throughout their pregnancies, and maternal/cord blood at birth, in addition to the placenta. This trial will test the hypothesis that choline supplementation increases the amount of PC-DHA in the blood of pregnant women and increase its supply to the developing fetus.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Kevin C. Klatt, PhD, RD
  • Phone Number: 267-978-8889
  • Email: klatt@bcm.edu

Study Locations

  • United States
    • New York
      • Ithaca, New York, United States, 14853
        • Recruiting
        • Human Metabolic Research Unit, Cornell University
        • Contact:
        • Principal Investigator:
          • Marie A. Caudill, PhD, RD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • healthy, singleton pregnant women gestational weeks 12-16, ages 21-40, willingness to comply with the study protocol

Exclusion Criteria:

  • Habitually high choline/DHA intake
  • Pre-pregnancy BMI >32
  • Pregnancy complications and comorbidities (at baseline and throughout the study)
  • Current smokers, drinkers, or drug users

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Placebo
Administration of the deuterated choline chloride will take place in a grape juice cocktail solution. For individuals in the placebo arm of the trial, no additional choline chloride will be added to the cocktail.
Experimental: Supplemental Choline
Administration of the deuterated choline chloride will take place in a grape juice cocktail solution. For individuals in the experimental arm of the trial, supplemental choline chloride will be added to the cocktail.
Dietary supplement: Choline
Choline chloride is a water soluble choline salt that will be provided in a juice solution to participants to be consumed daily. The intervention will increase dietary choline intake by 500mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DHA-Containing Phosphatidylcholine Species in Circulating Erythrocytes
Time Frame: Gestational Weeks 12-16 through Gestational Weeks 38-41
Phosphatidylcholine species contain 2 fatty acid tails; phosphatidylcholines containing DHA at either the sn-1 or sn-2 positions are found circulating in erythrocytes and serve as a long term marker of DHA status. Erythrocyte PC-DHA is partially supplied by albumin bound lysophosphatidylcholine enriched with DHA, a product of the phosphatidylethanolamine methyltransferase pathway in the liver, which has been shown to be sensitive to dietary choline intakes in non-pregnant women.
Gestational Weeks 12-16 through Gestational Weeks 38-41

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Circulating labeled and unlabeled choline metabolites in maternal plasma
Time Frame: Gestational Weeks 12-16 through Gestational Weeks 38-41
The concentrations and isotopic enrichments of choline and its metabolites (betaine, dimethylglycine,sarcosine, total phosphatidylcholine) will be determined in the maternal, placental and fetal compartments by Liquid Chromatography Tandem Mass Spectrometry
Gestational Weeks 12-16 through Gestational Weeks 38-41
The impact of dietary choline on total DHA concentrations in the maternal, fetal and placental compartments
Time Frame: Gestational Weeks 12-16 through Gestational Weeks 38-41
The total concentrations of docosahexaenoic acid (DHA; % total fatty acids as determined by Gas Chromatography-Flame Ionization Detector) will be measured in the maternal blood throughout this study. Additionally, at term, placenta and cord blood will be collected and analyzed for total DHA measurements.
Gestational Weeks 12-16 through Gestational Weeks 38-41
The Association of Maternal Choline Supplementation with Infant Visual Recognition Memory Novelty Score
Time Frame: 5, 7, 10, and 13 months of age
The composite novelty score (proportion of looking to the novel image) is obtained from a series of 9 visual paired comparison tests. The novelty score is a measure of visual recognition memory for infants and has been shown to predict cognitive outcomes in childhood.
5, 7, 10, and 13 months of age
The Association of Maternal Choline Supplementation with Infant Visual Attention Orienting Speed Score
Time Frame: 5, 7, 10, and 13 months of age
Visual attention orienting speed is measured by the latency to initiate a stimulus-guided fixation shift to a peripheral visual target (mean of up to 20 target presentations). The orienting score was found to be sensitive to maternal choline supplementation in infants of this age and has shown acceptable test-retest reliability and prediction of attention, memory, and intelligence quotient outcomes in childhood.
5, 7, 10, and 13 months of age
The Association of Maternal Choline Supplementation with Infant Sustained Focused Attention Score
Time Frame: 5, 7, 10, and 13 months of age
Sustained focused attention is measured during a 5-minute period in which infants are engaged in solitary play with a complex toy. The score is the average duration of infant engagement in a state of focused attention on the toy. Infants who sustain focused attention for longer durations have been found to have fewer attentional problems as children.
5, 7, 10, and 13 months of age
The Association of Maternal Choline Supplementation with Infant Recall Memory Score
Time Frame: 13 months of age
Recall memory is measured with a deferred imitation protocol. The infant watches an adult perform a novel sequence of actions on a set of objects to produce an interesting result. After a distraction-filled 15-minute delay the infant is given the objects and encouraged to engage in the modeled actions. The score is the number of target actions reproduced (average of 3 problems). Infants who achieve greater recall memory scores perform better on tests of memory during childhood.
13 months of age

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maternal choline intake and microbiome composition
Time Frame: Gestational Weeks 12-16 through Gestational Weeks 38-41 and neonatal month 3
Assess the effect of maternal choline intake during pregnancy on the maternal and neonatal gut microbiome, and the effect of the maternal microbiome on biomarkers of maternal status.
Gestational Weeks 12-16 through Gestational Weeks 38-41 and neonatal month 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cornell University

Collaborators

Balchem Corporation

Investigators

  • Principal Investigator: Marie A. Caudill, PhD, RD, Cornell University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 5, 2017

Primary Completion (Anticipated)

December 5, 2021

Study Completion (Anticipated)

December 5, 2021

Study Registration Dates

First Submitted

June 13, 2017

First Submitted That Met QC Criteria

June 19, 2017

First Posted (Actual)

June 21, 2017

Study Record Updates

Last Update Posted (Actual)

January 18, 2020

Last Update Submitted That Met QC Criteria

January 15, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB #: 1702006936

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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