Supplemental Choline and Brain Development in Humans

This study has been completed.
Sponsor:
Collaborator:
Egg Nutrition Center
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00678925
First received: May 14, 2008
Last updated: June 16, 2010
Last verified: June 2010
  Purpose

Studies have shown that choline is a necessary part of the human diet. Choline is important in making membranes for all the cells in the body, and for making chemicals that are responsible for nerve function. Studies have also shown that choline improves memory of rats when they are given choline at early stages in their lives. The purpose of this study is to find out whether choline supplementation (provided as a choline dietary supplement) in pregnant women will improve memory function of their babies after they are born.

In this study, we hypothesize that high dietary choline consumption during pregnancy and lactation will:

  1. Increase maternal choline concentration in plasma
  2. Increase breast milk choline concentration
  3. Enhance memory performance in the children born of supplemented mothers

Condition Intervention
Healthy
Dietary Supplement: Phosphatidylcholine
Dietary Supplement: Corn oil placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Official Title: Supplemental Choline and Neurodevelopment in Humans

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Infant working memory [ Time Frame: 10 months & 12 months of age ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Breast milk choline concentration [ Time Frame: 45 & 90 days postpartum ] [ Designated as safety issue: No ]
  • Plasma choline concentrations [ Time Frame: 20 & 30 wks pregnancy, 45 & 90 days postpartum ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: December 2004
Study Completion Date: May 2008
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Choline supplement given from 18-weeks pregnancy through 90 days postpartum
Dietary Supplement: Phosphatidylcholine
850 mg per day from 18 weeks pregnancy through 90 days postpartum
Other Name: PhosChol
Placebo Comparator: 2
Placebo capsules given from 18 weeks pregnancy through 90 days postpartum
Dietary Supplement: Corn oil placebo
Placebo capsules containing corn oil given from 18 weeks pregnancy through 90 days postpartum

Detailed Description:

The development of brain during critical periods in embryogenesis is vulnerable to changes in diet, specifically changes in choline intake. Babies born of mothers eating more choline are smarter on memory testing. These effects of dietary choline have been repeatedly demonstrated in rodent models in a series of studies funded by the NIH during the last eight years. Specifically, prenatal choline supplementation in rats facilitates cognitive function and visuospatial memory, whereas choline deficiency impairs divided attention and accelerates the age-related decline in temporal processing. There are two sensitive periods in rat brain development during which treatment with choline produces long-lasting enhancement of spatial memory that is lifelong. The first occurs during embryonic days 12-17 (rats give birth on day 21) and the second, during postnatal days 16-30. Choline supplementation during these critical periods elicits a major improvement in memory performance at all stages of training on a 12-arm radial maze. These changes in memory are correlated with decreases in the threshold for induction of long-term potentiation and with biochemical changes. Choline supplementation in pregnant rats decreases choline acetyltransferase activity and increases phospholipase D (PLD) activity in the hippocampus of offspring. Also, it increases the size of the cell body of cholinergic neurons. In contrast choline deficiency increases the activity of cholinergic system, but does not affect the basal level of PLD activity in hippocampus. These long-lasting functional, anatomical, and biochemical alterations may be related to the changes in neurogenesis and differentiation in fetal hippocampus and septum, areas of brain that are important for normal spatial learning and memory.

It is not known if these findings in rodents are likely to be true in humans, as human and rat brains mature at different rates. Moreover, rat brain is comparatively more mature at birth than is the human brain, but in humans hippocampal development may start around 20 weeks gestation and continue for months after birth. However, everything we know about brain development tells us that the processes seen in rodents are the same as those that occur in the developing human brain. For this reason, it is extremely likely that the robust effects we observe for choline in rodent brain have importance in the human. The research is the first major study in humans to determine whether maternal diet and diet during the baby's first year influences brain function.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Less than 18 weeks pregnant
  • Intends to breastfeed
  • Receives regular prenatal care
  • Takes a prenatal vitamin

Exclusion Criteria:

  • Uses tobacco or illicit drugs
  • Consumes alcohol
  • History of chronic illness
  • History of allergy to soy or corn
  • Difficulty swallowing large capsules
  • BMI <18 or >35
  • Pregnant with more than 1 fetus
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00678925

Locations
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27514
Sponsors and Collaborators
The Gerber Foundation
Egg Nutrition Center
  More Information

No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Steve H. Zeisel, MD, PhD, University of North Carolina at Chapel Hill
ClinicalTrials.gov Identifier: NCT00678925     History of Changes
Other Study ID Numbers: 04-1752 (completed)
Study First Received: May 14, 2008
Last Updated: June 16, 2010
Health Authority: UNC School of Medicine Data Safety Monitoring Board

ClinicalTrials.gov processed this record on October 29, 2014