Choline Supplements for Gestational Diabetes

Overseen By Itamar Futterman, MD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Maimonides Medical Center

Disqualifiers: Diabetes, Cardiovascular, Liver disease, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a choline supplement can help manage gestational diabetes, a condition where pregnant women experience high blood sugar. Researchers seek to understand if choline can normalize how the placenta transports nutrients, potentially reducing the risk of the baby growing too large. Pregnant women with gestational diabetes before week 28, carrying one baby, and planning to deliver at Maimonides Medical Center might be suitable candidates. Participants will take either a choline supplement or a placebo for 8 weeks to observe any effects on fetal growth. As an unphased trial, this study provides a unique opportunity to contribute to understanding how choline might benefit pregnant women with gestational diabetes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that choline supplements are generally safe for pregnant women. Studies have found that taking up to 3500 mg per day is safe. In this trial, the dose is 470 mg per day, well below that limit. Previous research suggests that choline can benefit both the mother and the baby during pregnancy. However, more studies are needed to fully understand all the benefits and any possible side effects. Overall, choline supplements are considered safe at the doses used in similar studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for gestational diabetes, which typically involve lifestyle changes and insulin therapy, choline supplements offer a unique approach by targeting nutrient supplementation. Choline is an essential nutrient that plays a critical role in fetal brain development and metabolic processes. Researchers are excited about choline because it may help improve glucose metabolism and reduce insulin resistance, potentially offering a simpler, non-invasive option for managing gestational diabetes. This novel approach could complement existing therapies and provide additional support for those struggling to manage their condition with standard methods.

What evidence suggests that choline supplements might be an effective treatment for gestational diabetes?

This trial will compare the effects of choline supplements with a placebo in pregnant women with gestational diabetes. Research has shown that choline supplements might improve how the placenta manages nutrients, potentially leading to healthier baby growth and reducing the risk of excessive size. In animal studies, choline supplements balanced how the placenta handled fat and sugar, supporting normal growth and fat levels in babies. Another study found that choline improved insulin use and reduced body weight in offspring. These findings suggest that choline could help manage growth issues in babies related to gestational diabetes. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for pregnant women diagnosed with gestational diabetes before week 28 of pregnancy, who are over 18, speak English or Spanish, and plan to deliver at Maimonides Medical Center. It's only for those with a single baby (singleton pregnancy) and not for those with heart conditions, liver disease, or pre-existing high blood sugar.

Inclusion Criteria

Intending to deliver their babies at Maimonides Medical Center

You are pregnant with only one baby.

Pregnant women with gestational diabetes before the 28th week of pregnancy.

Exclusion Criteria

I have high blood sugar levels.

I have diabetes.

I had heart or liver conditions before getting pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive choline supplement or placebo for 8 weeks starting after gestational week 28

8 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including birthweight and gene expression analysis at birth

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Choline supplement
• Placebo

Trial Overview The study tests if taking choline supplements (470mg/day) can help manage fetal growth in pregnancies affected by gestational diabetes. Women will be randomly assigned to receive either the choline supplement or a placebo starting after the 28th week of pregnancy and continuing for 8 weeks.

How Is the Trial Designed?

Group I: Choline Supplement Group Active Control 1 Intervention

Choline Supplement 470 mg twice daily for total of 8 weeks.

Group II: Placebo Group Placebo Group 1 Intervention

Placebo pill twice daily for total of 8 weeks.

Choline supplement is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Choline supplement for:

• Prenatal nutrition
• Fetal development support

Approved in Canada as Choline supplement for:

• Prenatal nutrition
• Fetal development support

Approved in European Union as Choline supplement for:

• Prenatal nutrition
• Fetal development support

Who Is Running the Clinical Trial?

Maimonides Medical Center

Lead Sponsor

Trials

72

Recruited

15,400+

Published Research Related to This Trial

Choline requirements are significantly higher for preterm infants (50-60 mg/kg/day) compared to term infants (17-18 mg/kg/day), highlighting the importance of adequate choline intake during rapid organ growth in the third trimester.

Most infant formulas do not provide sufficient choline or the appropriate types of choline components found in breast milk, indicating a need for reformulation and clearer labeling to ensure infants receive adequate choline for healthy development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choline Content of Term and Preterm Infant Formulae Compared to Expressed Breast Milk-How Do We Justify the Discrepancies? Shunova, A., Böckmann, KA., Minarski, M., et al.[2021]

Choline is essential during pregnancy for critical functions such as brain development, neurotransmission, and gene expression, highlighting its importance for both maternal and fetal health.

Most pregnant women in the U.S. do not meet the recommended choline intake of 450 mg/day, suggesting that dietary or supplemental increases in choline could improve pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choline: Exploring the Growing Science on Its Benefits for Moms and Babies. Korsmo, HW., Jiang, X., Caudill, MA.[2020]

Prenatal choline supplementation of 550 mg/d significantly increased maternal plasma levels of choline and its metabolites, such as betaine and phosphatidylcholine, compared to a lower dose of 25 mg/d, indicating enhanced choline metabolism during pregnancy.

The study suggests that higher choline intake supports metabolic adaptations necessary for both maternal and fetal health, with specific biomarkers identified for monitoring nutritional status during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choline metabolome response to prenatal choline supplementation across pregnancy: A randomized controlled trial. Taesuwan, S., McDougall, MQ., Malysheva, OV., et al.[2022]

In a study of 368 pregnant women, maternal dietary choline intake significantly influenced maternal and cord plasma concentrations of choline and its metabolites, with maternal levels increasing during pregnancy.

Fetal genetic variants did not predict the concentrations of choline and its metabolites in cord plasma, suggesting that maternal choline status is more critical for fetal development than genetic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations. Visentin, CE., Masih, S., Plumptre, L., et al.[2023]

Maternal betaine supplementation in obese mice prevented fetal and placental overgrowth and downregulated key transporters and growth factors at an early stage of pregnancy (E12.5), but these effects diminished by later stages (E17.5).

At E17.5, betaine supplementation reduced fetal fat accumulation and liver triglyceride levels, while enhancing the expression of a gene that supports fat metabolism, indicating that betaine may have a unique role in managing fetal metabolic health compared to choline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal betaine supplementation affects fetal growth and lipid metabolism of high-fat fed mice in a temporal-specific manner. Joselit, Y., Nanobashvili, K., Jack-Roberts, C., et al.[2019]

Low maternal choline intake is linked to a higher risk of neural tube defects (NTDs), with a pooled estimate indicating a 36% increased odds for NTDs among mothers with low choline levels based on a meta-analysis of 5 case-control studies involving over 5,500 mothers.

Higher maternal choline intake during pregnancy (550 mg to 1 g/day) and early postnatal periods is associated with improved neurocognitive outcomes in children, suggesting that increasing choline intake could enhance memory, attention, and learning abilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between Maternal Choline, Fetal Brain Development, and Child Neurocognition: Systematic Review and Meta-Analysis of Human Studies. Obeid, R., Derbyshire, E., Schön, C.[2023]

In a pilot study of 16 pregnant women in Jamaica, the average dietary choline intake was found to be significantly below the recommended level of 450 mg/day, with a mean intake of only 278.5 mg.

The mean plasma choline concentration in these women was 8.4 micromol/L, which is lower than the normal levels for both non-pregnant individuals and pregnant women, suggesting potential nutritional inadequacy that could affect fetal development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary intake of choline and plasma choline concentrations in pregnant women in Jamaica. Gossell-Williams, M., Fletcher, H., McFarlane-Anderson, N., et al.[2022]

Pregnant Wistar rats that received a high choline diet led to male offspring with better metabolic health when they were later fed a high-fat diet, showing lower body weight, reduced adiposity, and improved insulin sensitivity compared to those whose mothers had a standard choline diet.

In contrast, when the offspring were weaned to a normal fat diet, those from high choline mothers had increased food intake and body weight, indicating that the benefits of choline supplementation are more pronounced in a high-fat dietary context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Choline Intake during Pregnancy Reduces Characteristics of the Metabolic Syndrome in Male Wistar Rat Offspring Fed a High Fat But Not a Normal Fat Post-Weaning Diet. Hammoud, R., Pannia, E., Kubant, R., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10709661/

Choline Supplementation in Pregnancy: Current Evidence ... Choline supplementation shows promise in enhancing both maternal and fetal health. However, its full benefits can only be realized through further research.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04302168

Choline Supplementation on Fetal Growth in Gestational ... Previous research demonstrated that maternal choline supplementation (MCS) normalized placental fat and glucose transport as well as fetal growth and fat mass ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0955286324002377

Prenatal choline supplementation enhances metabolic ... Prenatal choline supplementation led to higher insulin sensitivity in female offspring at weaning as well as lower body weight and food intake.

4. grantome.com grantome.com/grant/NIH/SC2-DK108292-01

Effects of choline on fetal growth and lipid accretion in ... We hypothesize that maternal choline supplementation will prevent GDM-induced macrosomia and excessive adiposity across the lifespan of the offspring. In Aim 1, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6988845/

Maternal choline supplementation during the third trimester of ... Rodent studies demonstrate that supplementing the maternal diet with choline during pregnancy produces life-long cognitive benefits for the offspring.

6. mdpi.com mdpi.com/2072-6643/16/11/1767

Choline—An Underappreciated Component of a Mother-to- ... The results of this study showed that children of women who supplemented during pregnancy with a higher dose of choline (930 mg/d) were better at correctly ...

7. cda-amc.ca cda-amc.ca/sites/default/files/pdf/htis/2024/RC1531%20Choline%20Supplementation.pdf

Choline Supplementation for Infants, Children, and ... One RCT27 conducted a power calculation and found statistically significant results for some outcomes, the authors of the other RCTs indicated that Page 15 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11576091/

Choline and betaine intakes during pregnancy in relation ... No significant correlation was observed between the consumption of choline or betaine and incident GDM (adjusted OR (95 % CI), 0·77 (0·41, 1·43) ...