Effect of Vitamin C, D and Zinc Supplementation on the Immune and Inflammatory Process in Type 2 Diabetic Subjects

Sponsor

Universidad Autonoma del Estado de Mexico (Other)

Overall Status

Unknown status

CT.gov ID

NCT03734445

Collaborator

(none)

120

Enrollment

Arms

2.5

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Type 2 Diabetes Mellitus According to the World Health Organization (WHO), there are more than 346 million individuals with diabetes, of which 90% are type 2. Global estimations for the year 2030 predict an epidemic increase that will reach 366 million. According to the National Nutrition and Health Survey of 2006 (ENSANUT2005), there are 6.4 million type 2 diabetic subjects in Mexico.

According to the calculation of the sample size, the investigators will include 120 adults with type 2 diabetes mellitus selected from the outpatient preventive medicine offices of health centres in the State of Mexico who will divided in two groups: supplement and placebo (60 per group). After having been invited to participate and obtaining the informed consent, study subjects will be evaluated for dietary information, as well as biochemical biomarkers of metabolic control, anthropometric, immune and inflammatory markers, gut microbiota and oxidative stress, before beginning the trial, and after 12 and 24 weeks of supplementation. They will have a monthly follow-up visit for evaluation of adherence and adverse effects, as well as delivery of the supplement.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Dietary Supplement: Vitamin Supplement Other: Placebo	N/A

Detailed Description

Subjects will be randomly allocated to a supplementation with 1000 mg vitamin C, 400 IU vitamin D and 10 mg of zinc or placebo group, during 24 weeks. Subjects and researchers will be blinded to the supplement or placebo in order to guarantee double-blinding.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects will be randomly allocated to two groups (vitamin supplement or placebo), with a duration of 24 weeks. Dietary and compliance monthly follow-up and baseline, 12 and 24-week measurements.Subjects will be randomly allocated to two groups (vitamin supplement or placebo), with a duration of 24 weeks. Dietary and compliance monthly follow-up and baseline, 12 and 24-week measurements.

Masking:

Double (Participant, Investigator)

Masking Description:

Vitamin Supplement and placebo will be packaged by others not including the investigators, code will be kept secret until the end of the trial or unless a secondary effect is registered and merits the opening of the code

Primary Purpose:

Treatment

Official Title:

Effect of Vitamin C, Vitamin D and Zinc Supplementation on the Immune and Inflammatory Process in Type 2 Diabetic Subjects in Mexico

Anticipated Study Start Date :

Jan 9, 2020

Anticipated Primary Completion Date :

Jan 9, 2020

Anticipated Study Completion Date :

Mar 26, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin supplement Effervescent tablets containing Vitamin C, Vitamin D and zinc	Dietary Supplement: Vitamin Supplement Subjects will be randomly allocated to a supplementation of vitamin C 1000mg, vitamin D 400 IU and zinc 10 mg or an identical placebo. Subjects and researchers will be blinded to the supplement or placebo in order to guarantee double-blinding
Placebo Comparator: Placebo Effervescent tablets not containing Vitamin C, Vitamin D and zinc	Other: Placebo Subjects will be randomly allocated to a supplementation of an identical placebo. Subjects and researchers will be blinded to the supplement or placebo in order to guarantee double-blinding

Arm

Intervention/Treatment

Experimental: Vitamin supplement

Effervescent tablets containing Vitamin C, Vitamin D and zinc

Dietary Supplement: Vitamin Supplement

Subjects will be randomly allocated to a supplementation of vitamin C 1000mg, vitamin D 400 IU and zinc 10 mg or an identical placebo. Subjects and researchers will be blinded to the supplement or placebo in order to guarantee double-blinding

Placebo Comparator: Placebo

Effervescent tablets not containing Vitamin C, Vitamin D and zinc

Other: Placebo

Subjects will be randomly allocated to a supplementation of an identical placebo. Subjects and researchers will be blinded to the supplement or placebo in order to guarantee double-blinding

Outcome Measures

Primary Outcome Measures

Change in glycemia from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Measured in plasma with a Selectra II automated equipment with Randox reactants, in mg/dL
Change in glycosilated Hemoglobin (Hb1Ac) from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Measured in plasma with a Selectra II automated equipment with Randox reactants, in percentage
Change in plasma insulin from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Multiplex Technology in a Milliplex Luminex Equipment with Merck-Millipore reactants, in uU/mL
Change in Homeostatic Model Assesment for Insulin Resistance (HOMA-IR) from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Calculated from: HOMA-IR = (insulin x glucose)/405

Secondary Outcome Measures

Change in plasma cytokines from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Tumor Necrosis Factor alfa (TNFα), Interferon gamma (IFN-γ), Interleukins 1 beta, 4, 6 and 10 (IL-1β, IL4, IL-6, IL10) & transforming growth factor beta (TGF-β), measured with Multiplex Technology in a Milliplex Luminex Equipment with Merck-Millipore reactants, in pg/mL
Change in plasma adipokines from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Adiponectin, resistin and leptin, measured with Multiplex Technology in a Milliplex Luminex Equipment with Merck-Millipore reactants, in pg/mL
Change in additional plasma inflammatory markers from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Apolipoproteins A and B, C-reactive protein, vascular cell adhesion protein (V-CAM), intercellular adhesion molecule (I-CAM), complement proteins C-3 and C-4, measured with Multiplex Technology in a Milliplex Luminex Equipment with Merck-Millipore reactants, in pg/mL
Change in lipid profile from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Total cholesterol, HDL-, LDL-, Very Low Density Lipoprotein (VLDL)-cholesterol and triacylglycerides, measured in plasma with a Selectra II automated equipment with Randox reactants, in mg/dL
Changes in markers of oxidative stress from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Malondialdehyde (QuantiChromTM), Thiobarbituric acid reactive substances (TBARS Assay Kit), carbonylated proteins (colorimetric), antioxidant capacity (QuantiChromTM Antioxidant Assay Kit), catalase (EnzyChromTM Catalase Assay Kit), superoxide dismutase (EnzyChromTM Superoxide Dismutase Assay Kit) and glutathion peroxidase (metaphosphoric acid SIGMA ALDRICH y EnzyChromTM GSH/GSSG Assay Kit, measured with various commercial kits, in U/μL
Changes in lymphocyte subpopulations from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Cluster of desgination 4, 8, 17 and 19 (CD4+, CD8+, CD17+ and CD19+), measured by flow cytometry (Becton Dickinson Facs AriaMR de 6 canales), in percentage
Changes in Intestinal microbiota patterns from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Analyzed with a Illumina sequencing equipment and Mothur y Stamp softwares, in percentage

Other Outcome Measures

Change in plasma vitamin C from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Measured with a Colorimetric assay, in mg/dL
Changes in plasma vitamin D from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Measured with a commercial ELISA kit, ng/mL
Changes in plasma zinc from baseline to 12 and 24 weeks [Baseline, 12 and 24 weeks]
Measured with a Colorimetric assay, in mg/dL

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Between 25 and 55 years of age, as this is the age in which type 2 diabetes mellitus is more prevalent and there is less probability of encountering multiple diseases in the same subjects
Both sexes
Outpatients
BMI ≥ 25

Exclusion Criteria:

Without any other chronic disease (cancer, cardiovascular diseases, arthritis and Alzheimer's).
Severe renal insufficiency.
Nephrolithiasis or history of nephrolithiasis.
Hyperoxaluria.
Hemochromatosis.
Hypercalcaemia.
Hypervitaminosis D.
Using insulin.
Be taking drugs such as desferrioxamine, iron, cyclosporine, indinavir (protease inhibitors), warfarin, thiazide diuretic, orlistat, ion exchange resins (e.g cholestyramine, laxatives (e.g. mineral oil, senna), vitamin d analogues (e.g. ergocalciferol, calcitriol, and topical calcipotriene), tetracycline antibiotics, quinolone antibiotics, penicillamine, biphosphonates, levothyroxine, eltrombopag.
Patients with hypersensitivity to any of the active substance(s) or to any of the excipients.
Hypersensitivity to the by-products including honey, conifers, poplars, Peru balsam, and salicylate.
Intake of probiotics or supplemental vitamin or mineral (vitamin D, C, zinc or calcium) for 4 weeks before the beginning of the study.
Smoking and alcohol consumption (> 40 gr/ day for men and 25 gr/ day for women.
Pregnant or lactating.
Whose parents or grandparents are/were immigrant or of native origin.