Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000678897
Ethics application status
Approved
Date submitted
8/04/2021
Date registered
3/06/2021
Date last updated
25/04/2024
Date data sharing statement initially provided
3/06/2021
Date results information initially provided
9/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Micronutrient supplementation in metabolic syndrome
Scientific title
The effect of micronutrient supplementation on inflammation in metabolic syndrome
Secondary ID [1] 303257 0
None
Universal Trial Number (UTN)
U1111-1261-0076
Trial acronym
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Metabolic Syndrome 320670 0
Condition category
Condition code
Metabolic and Endocrine 318516 318516 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is an everyday oral micronutrient tablet (Bayer) which will be administered for 12 weeks.
Dose: 1 effervescent tablet
Route: dissolved in water for oral consumption
Frequency: once per day
Composition: 1000 mg vitamin C, 10 ug vitamin D, 45 mg vitamin E, 700 ug vitamin A, 6.5 mg vitamin B6, 400 ug folate, 9.6 ug vitamin B12, 10 mg zinc, 5 mg iron, 0.9 mg copper, 110 ug selenium
Intervention code [1] 319702 0
Treatment: Other
Comparator / control treatment
The placebo tablet will be an effervescent tablet and will not contain any active ingredient. It will be closely matched for appearance and flavour (Bayer).
Control group
Placebo

Outcomes
Primary outcome [1] 326485 0
Effect of intervention on plasma high-sensitivity C-reactive protein (hs-CRP) concentrations (Immunoturbidimetric, latex immunoassay)
Timepoint [1] 326485 0
Baseline (prior to intervention), 6 weeks and 12 weeks (primary endpoint) post the commencement of intervention.
Secondary outcome [1] 391642 0
Changes in plasma pro-inflammatory cytokines (TNF-a, IL-6) measured using ELISA
Timepoint [1] 391642 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [2] 391643 0
Changes in plasma glucose levels (glucose hexokinase enzymatic assay)
Timepoint [2] 391643 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [3] 391644 0
Changes in blood insulin concentrations (Roche Cobas e411 after PEG precipitation of immunoglobulins)
Timepoint [3] 391644 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [4] 391645 0
Changes in blood HbA1c concentrations (Bio-Rad D100, cation exchange HPLC)
Timepoint [4] 391645 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [5] 391646 0
Changes in plasma lipids: total cholesterol and HDL-Cholesterol (enzymatic cholesterol oxidase assay) and triglycerides (enzymatic hydrolysis), to calculate LDL-Cholesterol
Timepoint [5] 391646 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [6] 391647 0
Changes in oxidative stress marker urinary F2-isoprostanes (measured using ELISA)
Timepoint [6] 391647 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [7] 391648 0
Changes in antioxidant nutrient markers: plasma vitamin C and urate (measured using HPLC)
Timepoint [7] 391648 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [8] 391649 0
Changes in complete blood counts (CBC; Canterbury Health Laboratory)
Timepoint [8] 391649 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [9] 391650 0
Changes in plasma myeloperoxidase concentrations (MPO; ELISA)
Timepoint [9] 391650 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [10] 393853 0
Changes in weight (using a digital weigh scale), to calculate body mass index (BMI)
Timepoint [10] 393853 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [11] 395050 0
Changes in waist circumference (using a tape measure) to calculate waist/hip ratio
Timepoint [11] 395050 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [12] 395051 0
Changes in blood pressure (measured using a sphygmomanometer)
Timepoint [12] 395051 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [13] 395052 0
Changes in homeostatic model assessment for insulin resistance (HOMA-IR)
Timepoint [13] 395052 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [14] 395053 0
Changes in metabolic severity z score
Timepoint [14] 395053 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [15] 395054 0
Changes in subjective mood (Hospital Anxiety and Depression Scale - HADS)
Timepoint [15] 395054 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [16] 395055 0
Changes in fatigue (Multidimensional Fatigue Symptom Inventory - MFSI)
Timepoint [16] 395055 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.
Secondary outcome [17] 395056 0
Upper respiratory infection: Wisconsin Upper Respiratory Symptom Survey (WURSS)
Timepoint [17] 395056 0
Measured daily in the case of self-reported sickness during the 12-week intervention for the length of the illness.
Secondary outcome [18] 395057 0
Intervention compliance (assessed by plasma vitamin C status - HPLC)
Timepoint [18] 395057 0
Baseline (prior to intervention), 6 and 12 weeks post the commencement of intervention.

Eligibility
Key inclusion criteria
1 - Male or female aged greater than or equal to 18 years

2 - Central/abdominal obesity (i.e. waist circumference greater than or equal to 94 cm for males, greater than or equal to 80 cm for females or BMI greater than or equal to 30 kg/m2)

3 - And any two of the below:
a) Hyperglycemia (i.e. fasting glucose greater than or equal to 5.6 mmol/L or taking medication for this condition)
b) Raised triglycerides (i.e. TG greater than or equal to 1.7 mmol/L or taking medication for this condition)
c) Lowered HDL (HDL less than 1.0 mmol/L males, less than 1.3 mmol/L females or taking medication for this condition)
d) Hypertension (i.e. blood pressure greater than 130 systolic or greater than 86 diastolic or taking medication for this condition)

4 - CRP greater than 3mg/L (i.e. high risk of cardiovascular disease - CVD)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1 - Acute illness within previous 2 weeks

2 - Taking anti-inflammatory medication (e.g. corticosteroids)

3 - Suffering from inflammatory conditions (e.g. active malignancy, rheumatoid arthritis, lupus, inflammatory bowel disease)

4 - Pregnant or breastfeeding

5 - Taking micronutrient (vitamin/mineral) supplements

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be concealed in opaque sealed envelopes. Treatment and placebo tablets will be in identical containers and allocated in the order participants enter the trial. Treatment/placebo will be dispensed by research staff who will be blinded as to which arm participants are allocated to.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation will be concealed with a pre-specified computer-generated random block randomisation list prepared by the study statistician to ensure blinding. Participants will be randomised (1:1) to receive either one micronutrient tablet or placebo tablet.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analyses will be carried out by an experienced biostatistician. Participant characteristics will be summarised using descriptive statistics and tabulated by treatment group. The absolute between-group difference in mean hs-CRP at 12 weeks will be estimated with 95% confidence intervals (CI) using ordinary least squares regression adjusting for hs-CRP at baseline. Continuous secondary outcomes will be analysed similarly. Participants will be analysed as randomised and multiple imputation used if missing data exceeds 10%. Sensitivity analysis will investigate differences in outcomes according to treatment compliance and vitamin C levels achieved. Secondary analysis will establish differences at the earlier time point, which will also be used for imputation due to dropout. Linear mixed model will be used to assess all three time points.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/06/2021
Actual
28/07/2021
Date of last participant enrolment
Anticipated
14/11/2022
Actual
16/03/2023
Date of last data collection
Anticipated
8/06/2023
Actual
11/06/2023
Sample size
Target
70
Accrual to date
Final
72
Recruitment outside Australia
Country [1] 23444 0
New Zealand
State/province [1] 23444 0
Canterbury

Funding & Sponsors
Funding source category [1] 307666 0
Commercial sector/Industry
Name [1] 307666 0
Bayer Consumer Care
Country [1] 307666 0
Switzerland
Primary sponsor type
University
Name
University of Otago, Dunedin
Address
University of Otago
362 Leith Street
North Dunedin
Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 308362 0
None
Name [1] 308362 0
Address [1] 308362 0
Country [1] 308362 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307704 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 307704 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 307704 0
New Zealand
Date submitted for ethics approval [1] 307704 0
08/02/2021
Approval date [1] 307704 0
08/04/2021
Ethics approval number [1] 307704 0
21/STH/43

Summary
Brief summary
Metabolic syndrome (MetS) is a cluster of conditions that, when occurring together, increase the risk of heart disease, stroke and type-2 diabetes. These conditions include hypertension (high blood pressure), insulin resistance (high blood sugar), excess fat around the waist, and elevated cholesterol or triglyceride levels.

Inflammation is believed to be a major driver of MetS, and those with the condition often show increased levels of inflammatory markers in their blood, such as C-reactive protein (CRP), which is a known risk factor for cardiovascular diseases. As such, there is a growing interest in using anti-inflammatory agents to potentially slow and/or prevent progression of MetS to the more severe diseases such as type 2 diabetes and cardiovascular disease.

Vitamin C is a potent antioxidant with anti-inflammatory properties. Research has shown that people with MetS have lower vitamin C levels than those without, and higher vitamin C levels have been associated with a lower risk of MetS. Vitamin C can also improve markers of metabolic health, such a blood sugar control and lipid profiles, including cholesterol and triglycerides. Humans cannot produce vitamin C endogenously, therefore, we must obtain it through our diet.

The aim of this study is to determine whether vitamin C plus micronutrient supplementation of people with MetS and elevated inflammation results in decreased markers of inflammation. We will undertake a 12 week randomised controlled trial (1 daily effervescent micronutrient tablet or placebo) in a group of volunteers with MetS. We will measure a number of blood and urine markers of inflammation, glycaemic measures, lipid measures, anthropomorphic measures, and subjective mood/fatigue at clinic visits at baseline and weeks 6 and 12.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108206 0
A/Prof Anitra Carr
Address 108206 0
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
New Zealand
Country 108206 0
New Zealand
Phone 108206 0
+64 3 3640649
Fax 108206 0
Email 108206 0
[email protected]
Contact person for public queries
Name 108207 0
A/Prof Anitra Carr
Address 108207 0
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
New Zealand
Country 108207 0
New Zealand
Phone 108207 0
+64 3 3640649
Fax 108207 0
Email 108207 0
[email protected]
Contact person for scientific queries
Name 108208 0
A/Prof Anitra Carr
Address 108208 0
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
New Zealand
Country 108208 0
New Zealand
Phone 108208 0
+64 3 3640649
Fax 108208 0
Email 108208 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The de-identified individual participant data will not be available for this study as we do not have ethical approval to do this.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes A High Vitamin C Micronutrient Supplement Is Unabl... [More Details]

Documents added automatically
No additional documents have been identified.