Effect of Vitamin C, D and Zinc Supplementation on the Immune and Inflammatory Process in Type 2 Diabetic Subjects
Primary Purpose
Diabetes Mellitus, Type 2
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Vitamin Supplement
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Diabetes Mellitus type 2, Vitamin C, Vitamin D, Cinc
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Vitamin supplement
Placebo
Arm Description
Effervescent tablets containing Vitamin C, Vitamin D and zinc
Effervescent tablets not containing Vitamin C, Vitamin D and zinc
Outcomes
Primary Outcome Measures
Change in glycemia from baseline to 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
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
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
Calculated from: HOMA-IR = (insulin x glucose)/405
Secondary Outcome Measures
Change in plasma cytokines from baseline to 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
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
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
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
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
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
Analyzed with a Illumina sequencing equipment and Mothur y Stamp softwares, in percentage
Full Information
NCT ID
NCT03734445
First Posted
July 5, 2018
Last Updated
September 30, 2019
Sponsor
Universidad Autonoma del Estado de Mexico
1. Study Identification
Unique Protocol Identification Number
NCT03734445
Brief Title
Effect of Vitamin C, D and Zinc Supplementation on the Immune and Inflammatory Process in Type 2 Diabetic Subjects
Official Title
Effect of Vitamin C, Vitamin D and Zinc Supplementation on the Immune and Inflammatory Process in Type 2 Diabetic Subjects in Mexico
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Unknown status
Study Start Date
January 9, 2020 (Anticipated)
Primary Completion Date
January 9, 2020 (Anticipated)
Study Completion Date
March 26, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universidad Autonoma del Estado de Mexico
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Diabetes Mellitus type 2, Vitamin C, Vitamin D, Cinc
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantInvestigator
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
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Vitamin supplement
Arm Type
Experimental
Arm Description
Effervescent tablets containing Vitamin C, Vitamin D and zinc
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Effervescent tablets not containing Vitamin C, Vitamin D and zinc
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin Supplement
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in glycemia from baseline to 12 and 24 weeks
Description
Measured in plasma with a Selectra II automated equipment with Randox reactants, in mg/dL
Time Frame
Baseline, 12 and 24 weeks
Title
Change in glycosilated Hemoglobin (Hb1Ac) from baseline to 12 and 24 weeks
Description
Measured in plasma with a Selectra II automated equipment with Randox reactants, in percentage
Time Frame
Baseline, 12 and 24 weeks
Title
Change in plasma insulin from baseline to 12 and 24 weeks
Description
Multiplex Technology in a Milliplex Luminex Equipment with Merck-Millipore reactants, in uU/mL
Time Frame
Baseline, 12 and 24 weeks
Title
Change in Homeostatic Model Assesment for Insulin Resistance (HOMA-IR) from baseline to 12 and 24 weeks
Description
Calculated from: HOMA-IR = (insulin x glucose)/405
Time Frame
Baseline, 12 and 24 weeks
Secondary Outcome Measure Information:
Title
Change in plasma cytokines from baseline to 12 and 24 weeks
Description
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
Time Frame
Baseline, 12 and 24 weeks
Title
Change in plasma adipokines from baseline to 12 and 24 weeks
Description
Adiponectin, resistin and leptin, measured with Multiplex Technology in a Milliplex Luminex Equipment with Merck-Millipore reactants, in pg/mL
Time Frame
Baseline, 12 and 24 weeks
Title
Change in additional plasma inflammatory markers from baseline to 12 and 24 weeks
Description
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
Time Frame
Baseline, 12 and 24 weeks
Title
Change in lipid profile from baseline to 12 and 24 weeks
Description
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
Time Frame
Baseline, 12 and 24 weeks
Title
Changes in markers of oxidative stress from baseline to 12 and 24 weeks
Description
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
Time Frame
Baseline, 12 and 24 weeks
Title
Changes in lymphocyte subpopulations from baseline to 12 and 24 weeks
Description
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
Time Frame
Baseline, 12 and 24 weeks
Title
Changes in Intestinal microbiota patterns from baseline to 12 and 24 weeks
Description
Analyzed with a Illumina sequencing equipment and Mothur y Stamp softwares, in percentage
Time Frame
Baseline, 12 and 24 weeks
Other Pre-specified Outcome Measures:
Title
Change in plasma vitamin C from baseline to 12 and 24 weeks
Description
Measured with a Colorimetric assay, in mg/dL
Time Frame
Baseline, 12 and 24 weeks
Title
Changes in plasma vitamin D from baseline to 12 and 24 weeks
Description
Measured with a commercial ELISA kit, ng/mL
Time Frame
Baseline, 12 and 24 weeks
Title
Changes in plasma zinc from baseline to 12 and 24 weeks
Description
Measured with a Colorimetric assay, in mg/dL
Time Frame
Baseline, 12 and 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Available IPD and Supporting Information:
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Baothman+OA%2C+Zamzami+MA%2C+Taher+I%2C+ABugaker+J%2C+Abu-Farhca+MA.+The+role+of+Gut+Microbiota+in+the+development+of+obesity+and+diabetes
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Barengolts+E.+Vitamin+D+and+prebiotics+may+benefit+the+intestinal+microbacteria+and+improve+glucose+homeostasis+in+prediabetes+and+type+2+diabetes.
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Capdor+J%2C+Foster+M%2C+Petocz+P%2C+Samman+S.+Zinc+and+glycemic+control%3A+a+meta-analysis+of+randomised+placebo+controlled+supplementation+trials+in+humans.
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Fruit+and+vegetable+intake+and+the+association+with+glucose+parameters%3A+a+cross-sectional+analysis+of+the+Let%27s+Prevent+Diabetes+Study
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/15008827
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Foster+M%2C+Petocz+P%2C+Samman+S.+Inflammation+markers+predict+zinc+transporter+gene+expression+in+women+with+type+2+diabetes+mellitus
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Gokhale+NH%2C+Acharya+AB%2C+Patil+VS%2C+Trivedi+DJ%2C+Thakur+SL.+(2013)+A+short-term+evaluation+of+the+relationship+between+plasma+ascorbic+acid+levels+and+periodontal+disease+in+systemically+healthy+and+type+2+diabetes+mellitus+subjects
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Jansen+J%2C+Rosenkranz+E%2C+Overbeck+S%2C+Warmuth+S%2C+Mocchegiani+E%2C+Giacconi+R%2C+Weiskirchen+R%2C+Karges+W%2C+Rink+L.+Disturbed+zinc+homeostasis+in+diabetic+patients+by+in+vitro+and+in+vivo+analysis+of+insulinomimetic+activity+of+zinc
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/20606205
Available IPD/Information Type
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Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/22699609
Available IPD/Information Type
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Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Kayaniyil+S%2C+Vieth+R%2C+Retnakaran+R%2C+Knight+JA%2C+Qi+Y%2C+Gerstein+HC%2C+et+al.+Association+of+vitamin+D+with+insulin+resistance+and+beta-cell+dysfunction+in+subjects+at+risk+for+type+2+diabetes.+Diabetes+care
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Ley%2C+R.+E.%2C+Lozupone%2C+C.+A.%2C+Hamady%2C+M.%2C+Knight%2C+R.+%26+Gordon%2C+J.+I.+Worlds+within+worlds%3A+evolution+of+the+vertebrate+gut+microbiota
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Mandl+J%2C+Szarka+A%2C+Bángheyl.+(2009)+Vitamin+C%3A+update+on+physiology+and+pharmacology.+B+J+Pharmacol
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Efficacy+of+supplementary+vitamins+C+and+E+on+anxiety%2C+depression+and+stress+in+type+2+diabetic+patients%3A+a+randomized%2C+single-blind%2C+placebo-controlled+trial
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Effect+of+vitamin+C+supplementation+on+postprandial+oxidative+stress+and+lipid+profile+in+type+2+diabetic+patients.
Available IPD/Information Type
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Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/9794114
Available IPD/Information Type
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Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Rafighi%2C+Z.%2C+Shiva+A.%2C+Arab%2C+S.+and+Mohd+Yousof%2C+R.+(2013)+Association+of+dietary+vitamin+C+and+E+intake+and+antioxidant+enzymes+in+type+2+diabetes+mellitus+patients
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Zinc+as+a+potential+coadjuvant+in+therapy+for+type+2+diabetes.
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Sarmento+RA%2C+Silva+FM%2C+Sbruzzi+G%2C+Schaan+BD%2C+Almeida+JC.+Antioxidant+micronutrients+and+cardiovascular+risk+in+patients+with+diabetes%3A+a+systematic+review
Available IPD/Information Type
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Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/25284151
Available IPD/Information Type
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http://www.ncbi.nlm.nih.gov/pubmed/27915988
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Insulino-mimetic+and+anti-diabetic+effects+of+zinc
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/28615382
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/12502486
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/22375253
Available IPD/Information Type
scientific article
Available IPD/Information URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=Iman+M+Ibrahim%2C+and+Manal+M+Alkady.+Role+of+Vitamin+D+on+glycemic+control+and+oxidative+stress+in+type+2+diabetes+mellitus
Learn more about this trial
Effect of Vitamin C, D and Zinc Supplementation on the Immune and Inflammatory Process in Type 2 Diabetic Subjects
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