Effects of Vitamin D3 and Prebiotics Supplementation on Cardiovascular Risk Factors in Patients With Type 2 Diabetes

Effects of Vitamin D3 and Prebiotics Supplementation on Cardiovascular Risk Factors in Patients With Type 2 Diabetes: A Randomized Double-Blind Controlled Trial

The goal of this randomized, double-blind, placebo-controlled, 6-month supplementation study in individuals with type 2 diabetes is to investigate whether taking daily dietary supplements of vitamin D3 (1600 IU) or prebiotics (inulin, 10 gram) has beneficial effects on cardiovascular disease risk factors.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus, Type 2
• 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 trial, with a two-by-two factorial design in individuals with type 2 diabetes (T2D) is to investigate whether taking daily dietary supplements of vitamin D3 (1600 IU) or prebiotics (inulin, 10 gram) has beneficial effects on cardiovascular disease (CVD) risk factors.

About 200 subjects with T2D will be included in this study. All participants will provide written informed consent before randomization. Eligible participants must have no history of cancer, macrovascular or microvascular complications at trial entry, and they are required to agree to limited use of vitamin D, prebiotics, probiotics, or synbiotic supplementations, as well as to convenient access to study centers. Safety exclusions include renal failure or dialysis, cirrhosis, history of hypercalcemia, or other conditions that would preclude participation.

Eligible participants will be assigned by chance to one of four groups: (1) daily vitamin D3 (1600 IU) and prebiotics (10 grams); (2) daily vitamin D3 (1600 IU) and prebiotics placebo (10 grams); (3) daily vitamin D3 placebo and prebiotics (10 grams); or (4) daily vitamin D3 placebo (1600 IU) and prebiotics placebo (10 grams). Randomization will be computer-generated within sex and age groups.

During the run-in period, baseline questionnaires will be designed to collect data on sociodemographic factors, lifestyle habits, health status, and medical conditions, and participants will undergo physical measurements at baseline. Blood, urine, and faeces samples will also be obtained at study centers.

Participants in all groups will be required to take two capsules each day, containing either vitamin D3 or vitamin D3 placebo, as well as a strip of prebiotics powder (10 g per strip, brew with warm water) or prebiotics placebo. Participants will receive their capsules and powder at study centers each month.

Participants will complete follow-up questionnaires, including information on adherence to trial regimens, outside use of supplementations, development of major illnesses, and potential side effects of the trial agents, at 3 months and 6 months after randomization. Physical measurements and collection of biological samples will be conducted at study centers 6 months after randomization.

The primary outcomes, including glycated hemoglobin (HbA1c) and blood lipids (such as total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), will be measured using blood samples. The data will be collected and analyzed.

• Study Type: Interventional
• Enrollment (Estimated): 200
• 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: Tianyu Guo, BM; Phone Number: 86-18210047875; Email: m202275509@hust.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Type 2 diabetes (meeting any of the following criteria):

   Physician-diagnosed type 2 diabetes, use of oral hypoglycemic medication or insulin, fasting blood glucose ≥ 7.0 mmol/L, HbA1c ≥ 6.5% (48 nmol/L), 2-hour plasma glucose (2hPG) ≥ 11.1 mmol/L.

2. Men aged 40-69 years or women aged 40-69 years.
3. Convenient access to study centers.
4. Written informed consent obtained before any trial-related activities.

Exclusion Criteria:

1. History of macrovascular diseases (including Coronary heart disease, myocardial infarction, heart failure, stroke, transient ischemic attack, peripheral vascular disease, post coronary artery bypass surgery).
2. History of diabetic microvascular complications (including diabetic nephropathy, diabetic retinopathy, or diabetic neuropathy).
3. History of other cardiovascular diseases (including aortic stenosis, transient ischemic attack, angina pectoris, cardiac arrest, complex ventricular arrhythmias, or surgery of cardiovascular diseases).
4. History of cancer, excluding non-melanoma skin cancer or cancers with a good prognosis (such as stage 1 cervical cancer).
5. Severe liver disease (such as cirrhosis), severe kidney disease (such as renal failure or requiring dialysis), or severe gastrointestinal disease (such as a history of bowel obstruction).
6. Kidney stones, hypercalcemia, parathyroid hormone abnormality.
7. Sarcoidosis or other granulomatous diseases, such as active chronic pulmonary tuberculosis or Wegener's granulomatosis.
8. Any mental disorders, such as schizophrenia, other mental disorders, or bipolar disorder.
9. Individuals with infectious diseases such as HIV/AIDS, viral hepatitis.
10. Individuals requiring long-term hospitalization or those with other serious illnesses requiring immediate hospital treatment.
11. In the past 3 months, those who have taken any vitamin D supplements exceeding 400 IU/day, calcium supplements exceeding 600 mg/day, prebiotics exceeding 2 g/day, or probiotics exceeding 10^8 colony forming units/day.
12. History of allergy or intolerance to vitamin D, prebiotics, or starch.
13. Individuals with unhealthy habits: heavy alcohol consumption (>80 grams/day for males, >40 grams/day for females) or smoking (>40 cigarettes/day).
14. Individuals with cognitive impairment, inability to communicate properly, inability to take care of themselves, or those with mobility issues.
15. Those having participated in other clinical trials or studies in the past 3 months.
16. Those who are intent to become pregnant within the next two years, are currently pregnant, or breastfeeding.
17. Individuals with abnormal laboratory tests and clinical manifestations who are judged by the researcher to be unsuitable for participation.

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	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	Drug: Vitamin D3; Vitamin D3 (cholecalciferol), 1600 IU per day.; Other Names: Cholecalciferol; Dietary supplement: Prebiotics placebo; Prebiotics placebo, 10g per day.
Active Comparator: Prebiotics +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	Dietary supplement: Vitamin D3 placebo; Vitamin D3 placebo; Dietary supplement: Prebiotics placebo; Prebiotics placebo, 10g per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycated hemoglobin (HbA1c)	Concentration of HbA1c, measured in the percentage of hemoglobin	6 months
Concentration of blood lipids	Concentration of blood lipids (total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), measured in mmol/L	6 months
Metagenomic analysis of the gut microbiota	The diversity of the gut microbiota will be assessed by high-quality whole-metagenomic sequencing	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of fasting glucose	Concentration of fasting glucose, measured in mmol/L	6 months
Concentration of fasting insulin	Concentration of fasting insulin, measured in milli-International unit/L	6 months
Systolic and diastolic blood pressure	The level of systolic blood pressure and diastolic blood pressure, measured in mmHg	6 months
Estimated glomerular filtration rate (eGFR)	Calculating the level of eGFR using Chronic Kidney Disease Epidemiology Collaboration equation	6 months
Concentration of C-reactive protein (CRP)	Concentration of CRP, measured in mg/dL	6 months
Concentration of procalcitonin	Concentration of procalcitonin, measured in pg/mL	6 months
Concentration of interleukin-6 (IL-6)	Concentration of IL-6, measured in pg/mL	6 months
Concentration of serum 25(OH)D	Concentration of serum 25(OH)D concentrations, measured in nmol/L	6 months
Body weight	Weight in kilograms	6 months
Waist circumference	Waist circumference in centimeters	6 months
Hip circumference	Hip circumference in centimeters	6 months

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 (Estimated): April 24, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: April 1, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Vitamin D; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Lipids; Blood Glucose; Prebiotics
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: VD3, Prebiotics in Diabetes

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