Effects of Vitamin D and Prebiotic Supplementation on Glucose Control During Pregnancy

Effects of Vitamin D and Prebiotic Supplementation on Glucose Control During Pregnancy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

The goal of this randomized, double-blind, placebo-controlled study included pregnant women at high risk of GDM at 6-15 weeks of gestation is to investigate whether supplementation with vitamin D (1600 IU per day) or prebiotics (inulin, 10 gram per day) during pregnancy has beneficial effects on controlling blood glucose during pregnancy.

Study Overview

• Status: Recruiting
• Conditions: Glucose Intolerance During Pregnancy
• Intervention / Treatment: Dietary supplement: Vitamin D3 placebo; Drug: Vitamin D3; Dietary supplement: Prebiotics; Dietary supplement: Prebiotics placebo

Detailed Description

The goal of this randomized, double-blind, placebo-controlled study included pregnant women at high risk of GDM at 6-15 weeks of gestation is to investigate whether supplementation with vitamin D (1600 IU per day) or prebiotics (inulin, 10 gram per day) during pregnancy has beneficial effects on controlling blood glucose during pregnancy.

About 500 pregnant women aged 18-45 years, at 6-15 weeks of gestation, had resided locally for at least one year, with high risk of GDM will be enrolled in the study. Pregnant women at high risk of GDM are defined as meeting any of the following criteria:

1. Pre-pregnancy body mass index (BMI) ≥24.0 kg/m2;
2. History of GDM or a family history of diabetes;
3. History of delivery of macrosomia (birth weight >4000 g);
4. Glycated hemoglobin (HbA1c) 5.7-6.4% or fasting blood glucose 5.6-7.0 mmol/L; Eligible participants must have singleton pregnancy, no infertility treatment, no history of diabetes or a definite diagnosis of diabetes, or impaired glucose tolerance at recruitment (fasting blood glucose >7.0 mmol/L or HbA1c≥6.5%), no allergic history of chicory root and they will be required to agree to limit the use of vitamin D, prebiotics, probiotics, or synbiotic supplementations and to be convenient access to study centers. Safety exclusions include serious chronic or infectious diseases, serious liver or kidney disease, abnormalities in calcium metabolism, and clinically diagnosed mental disorders, or other conditions that would preclude participation.

Eligible participants will be assigned by chance to one of four groups: (1) daily vitamin D (1600 IU) and prebiotics (10 gram); (2) daily vitamin D (1600 IU) and prebiotics placebo; (3) daily vitamin D placebo and prebiotics (10 gram); or (4) daily vitamin D placebo and prebiotics placebo. Randomization will be conducted.

At enrollment, baseline questionnaires are designed to collect data on sociodemographic factors, pregnancy-related information, lifestyle habits, health status, and medical conditions before and during pregnancy. Participants in all groups will take two capsules that contained either vitamin D or vitamin D placebo and a strip of prebiotics powder (10 g per strip, brew with warm water and take with meals) or prebiotics placebo each day until delivery.

Participants will be followed up three times during pregnancy (24-28 weeks gestation, 32-36 weeks gestation and delivery), and receive a single stage-specific dosage at any given follow-up time.

Participants will have physical measurements of height, weight, other anthropometric measurements, and blood pressure at baseline and each follow-up visit. Blood, urine, and stool samples will also be obtained in the study center, fasting blood glucose, HbA1c and other biochemical indicators will also be detected at the same time, and a 75g oral glucose tolerance test (OGTT) will be measured during 24-28 weeks of gestation to diagnose GDM.

The primary outcomes, including fasting blood glucose and HbA1c will be measured using blood samples.

Secondary outcomes in this study include incidence of GDM, changes in blood lipids (such as total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), trends in plasma vitamin D levels, inflammatory factors, intestinal flora related indicators, delivery mode, incidence of preeclampsia and adverse pregnancy outcomes. Data will be collected and analyzed.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gang Liu, PHD; Phone Number: 86-15926238366; Email: liugang026@hust.edu.cn
• Study Contact Backup: Name: Yuwei Lai, BM; Phone Number: 86-13247125977; Email: laiyuwei918@163.com

Study Locations

• China
  • Guangdong
    • Zhanjiang, Guangdong, China
      • Recruiting
      • Central People's Hospital of Zhanjiang
      • Contact: Xingyue Song; Phone Number: 18040520787
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Tongji Medical College, Huazhong University of Science and Technology
      • Principal Investigator: Gang Liu
      • Contact: Yuwei Lai; Phone Number: 13247125977
      • Principal Investigator: An Pan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 6-15 weeks of gestation.
2. Age 18-45 years old.
3. Permanent resident or resident locally at least one year.

4. GDM high-risk pregnant women (meeting any of the following criteria):

   1. Pre-pregnancy body mass index (BMI) ≥24.0 kg/m2,
   2. History of GDM or a family history of diabetes,
   3. History of delivery of macrosomia (birth weight >4000 g),
   4. HbA1c 5.7-6.4% or fasting blood glucose 5.6-7.0 mmol/L.

Exclusion Criteria:

1. Multiple pregnancy.
2. Have received infertility treatment such as in vitro fertilization or intrauterine insemination.
3. History of diabetes or current diagnosis of diabetes (including type 1 and type 2 diabetes) or abnormal glucose tolerance at recruitment (fasting blood glucose >7.0 mmol/L or HbA1c≥6.5%).
4. Serious chronic diseases (including cardiovascular and cerebrovascular diseases, cancer, and thyroid dysfunction) or infectious diseases (including hepatitis B, active tuberculosis, acquired immunodeficiency syndrome, and syphilis).
5. Severe liver disease (such as cirrhosis) or severe kidney disease (such as renal failure or requiring dialysis).
6. Kidney stones, hypercalcemia, hypercalciuria, parathyroid hormone abnormality.
7. Any mental disorders, such as schizophrenia, depression, other mental disorders, or bipolar disorder.
8. History of allergy or intolerance to vitamin D, chicory root, or starch.
9. Have participated in or are participating in other clinical trials within the past 3 months.
10. Daily vitamin D intake >800 IU.
11. Inability or refusal to answer and communicate.
12. Those who are unwilling to sign the informed consent.
13. The researcher thinks that it is not suitable to participate in this research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D3 + Prebiotics; Vitamin D3 (cholecalciferol), 1600 IU per day. Prebiotics (inulin), 10g per day.	Drug: Vitamin D3; Vitamin D3 (cholecalciferol), 1600 IU per day.; Other Names: Cholecalciferol; Dietary supplement: Prebiotics; Prebiotics (inulin), 10g per day.; Other Names: Inulin
Active Comparator: Vitamin D3 + Prebiotics placebo; Vitamin D3 (cholecalciferol), 1600 IU per day. Prebiotics placebo.	Drug: Vitamin D3; Vitamin D3 (cholecalciferol), 1600 IU per day.; Other Names: Cholecalciferol; Dietary supplement: Prebiotics placebo; Prebiotics placebo.
Active Comparator: Prebiotics +Vitamin D3 placebo; Prebiotics (inulin), 10g per day. Vitamin D3 placebo.	Dietary supplement: Vitamin D3 placebo; Vitamin D3 placebo; Dietary supplement: Prebiotics; Prebiotics (inulin), 10g per day.; Other Names: Inulin
Placebo Comparator: Vitamin D3 placebo + Prebiotics placebo; Vitamin D3 placebo. Prebiotics placebo.	Dietary supplement: Vitamin D3 placebo; Vitamin D3 placebo; Dietary supplement: Prebiotics placebo; Prebiotics placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of fasting blood glucose	Concentration of fasting blood glucose, measured in mmol/L	24-28 gestational weeks, 32-36 gestational weeks, and delivery
Glycated hemoglobin (HbA1c)	Concentration of HbA1c, measured in the percentage of hemoglobin	24-28 gestational weeks, 32-36 gestational weeks, and delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Gestational Diabetes	75g oral glucose tolerance test (OGTT) will be performed at 24-28 weeks of gestation to diagnose gestational diabetes	24-28 gestational weeks
Concentration of blood lipids	Concentration of blood lipids (total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), measured in mmol/L	24-28 gestational weeks, 32-36 gestational weeks, and delivery
Concentration of plasma 25(OH)D	Concentration of plasma 25(OH)D concentrations, measured in nmol/L	24-28 gestational weeks, 32-36 gestational weeks, and delivery
Concentration of C-reactive protein (CRP)	Concentration of CRP, measured in mg/dL	24-28 gestational weeks, 32-36 gestational weeks, and delivery
Concentration of interleukin-6 (IL-6)	Concentration of IL-6, measured in pg/mL	24-28 gestational weeks, 32-36 gestational weeks, and delivery
Metagenomic analysis of the gut microbiota	The diversity of the gut microbiota will be assessed by high-quality whole-metagenomic sequencing	24-28 gestational weeks, 32-36 gestational weeks, and delivery
Birth weight	The baby's weight at birth, Weight in grams	Delivery
Gestational duration	The length of a woman's pregnancy from the start of her last period, duration in days	Delivery
Delivery mode	Method of the baby being born during childbirth, vaginal delivery or cesarean section	Delivery

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology
• Investigators: Principal Investigator: Gang Liu, PHD, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology; Principal Investigator: An Pan, PHD, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 11, 2024
• First Submitted That Met QC Criteria: August 11, 2024
• First Posted (Actual): August 14, 2024

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Vitamin D; Blood Glucose; Prebiotics; Adverse pregnancy outcomes; Glucose Intolerance During Pregnancy; Gestation diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Glucose Intolerance; Lipids; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Carbohydrates; Carbohydrates; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Polymers; Macromolecular Substances; Polysaccharides; Starch; Glucans; Biopolymers; Fructans; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Dietary Fiber; Polysaccharides, Bacterial; Cholecalciferol; Inulin; Prebiotics
• Other Study ID Numbers: VD, Prebiotics in Pregnancy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No