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Synergy Between Choline and DHA

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03194659
Recruitment Status : Recruiting
First Posted : June 21, 2017
Last Update Posted : January 18, 2020
Balchem Corporation
Information provided by (Responsible Party):
Cornell University

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

Condition or disease Intervention/treatment Phase
Pregnancy Dietary Supplement: Choline Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: All investigators interacting with participants will be masked to the study arm assignment. Only the Primary Investigator and Laboratory Manager (prepares supplements) will have access to participant's study assignment.
Primary Purpose: Basic Science
Official Title: Maternal Choline Supplementation and Its Impact on Docosahexaenoic Acid Supply in Human Pregnancy
Actual Study Start Date : October 5, 2017
Estimated Primary Completion Date : December 5, 2021
Estimated Study Completion Date : December 5, 2021

Resource links provided by the National Library of Medicine

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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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. 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.

  6. 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.

Other Outcome Measures:
  1. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   21 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03194659

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Contact: Marie A. Caudill, PhD, RD 607-254-7456
Contact: Kevin C. Klatt, PhD, RD 267-978-8889

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United States, New York
Human Metabolic Research Unit, Cornell University Recruiting
Ithaca, New York, United States, 14853
Contact: Erica Bender, MSN, CNM    607-255-9417   
Principal Investigator: Marie A. Caudill, PhD, RD         
Sponsors and Collaborators
Cornell University
Balchem Corporation
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Principal Investigator: Marie A. Caudill, PhD, RD Cornell University
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Responsible Party: Cornell University Identifier: NCT03194659    
Other Study ID Numbers: IRB #: 1702006936
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cornell University:
docosahexaenoic acid
fatty acids
Additional relevant MeSH terms:
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Lipotropic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents
Lipid Regulating Agents
Nootropic Agents