Clinical trial NCT02359214: Effect of Vitamin D3 Supplementation on Cardiometabolic Risk
Official title: Effect of Vitamin D3 Supplementation on Cardiometabolic Risk Factors in a Cohort of Overweight and Obese Adults in the United Kingdom (UK)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
Diabetes
Bone Disease
Keywords: Vitamin D
Cardiovascular disease
Diabetes
Obesity
Cardiometabolic
Bone disease
Lead sponsor: University of Chester
Sponsor class: OTHER
First posted: 2015-02-09
Enrollment: 49
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Supplementation studies with vitamin D have been performed where cardiometabolic risk markers have been assessed but these are few, and results are inconsistent. Hence, the purpose of this study is to determine:

1. Whether administering supplemental Vitamin D3 at a dose of 5000IU/day (125µg) in overweight and obese adult participants for 8 weeks will significantly increase circulating concentrations of 25(OH)D or achieve optimal vitamin D status.
2. Whether administering supplemental Vitamin D3 at a dose of 5000IU/day (125µg) in overweight and obese participants for 8 weeks will significantly improve the cardiometabolic parameters measured.
3. To evaluate the relationship between these variables and 25(OH)D concentration. We hypothesise that there will be a significant increase in plasma 25(OH)D following 8 weeks (56days) supplementation of oral vitamin D3 at a dose of 5000IU/day (125µg); Administering supplemental Vitamin D3 at a dose of 5000IU/day (125µg) in overweight and obese participants for 8 weeks will significantly improve the cardio metabolic parameters measured, and there will be a relationship between these variables and 25(OH)D concentrations.

Detailed description: This study is a parallel randomised, double-blind placebo - controlled trial which will be conducted at the University of Chester, Chester, United Kingdom. Ethical permission has been obtained through the University of Chester Faculty Research Ethics Committee(855/13/AT/CSN). Participants, especially students/staff will be recruited from the University of Chester by email, posters/leaflets.

Males were chosen for this study due to their higher risk of developing cardiometabolic diseases compared to premenopausal women. The participants will be randomised to receive either a vitamin D supplement (5000IU (125µg)/d) or placebo for eight weeks. A computer generated random number sequence will be used to assign participants to the intervention and placebo group. Eligibility will be based on 25(OH)D assessment made at a screening visit before the baseline visit, and participants with plasma 25(OH)D level ≤ 75nmol/l will be invited to participate in the study. To ensure compliance with the intervention, participants will be sent reminders about the intervention appointments by email or phone calls. The study will be performed according to the declaration of Helsinki. All participants will provide written consent. Study participants will be instructed to store the study supplements at room temperature. All unconsumed supplements will be returned and counted to assess compliance.

MEASUREMENTS Dietary intake will be estimated at baseline and post intervention using a three day food diary and information about health conditions, medications and health related behaviors will be assessed by a pre-screen test questionnaire, physical activity will be evaluated as the average of the metabolic equivalent of task (MET-min/week) using the International Physical Activity Questionnaire. Participants will be assessed at baseline (day 0), days 28 and 56. The plasma samples will be batch analyzed at the end of the trial.

ANTHROPOMETRIC MEASUREMENTS Height (m2) will be measured without shoes at baseline, using a stadiometer to the nearest 0.1cm precision, Body weight (kg) will be measured without shoes at baseline through post intervention using a digital scale with participants wearing light indoor clothing, BMI will be calculated as weight in kilograms divided by the square of height in meters (kg/m2), and waist circumference at the iliac crest will be measured with a tape measure with the subject standing.

PULSEWAVE VELOCITY AND BLOOD PRESSURE MEASUREMENTS Participants will be given a glass of water and allowed to rest for 5 minutes in a supine position and afterwards the pulse wave velocity meter (Arteriograph) cuff, for measuring arterial stiffness and blood pressure will be placed tightly round the dominant arm. Overall, three measurements will be performed but only the mean of two measurements will be taken.

BIOCHEMICAL MEASUREMENTS A morning blood sample will be collected by venepuncture from the antecubital vein according to standard protocols, with participants in a sitting position after an overnight fast of at least 8 hours. Blood samples will be drawn into 10ml lithium heparin and ethylene diamine triacetic acid (EDTA) tubes to avoid clotting after which they will be immediately transferred into an ice box and then centrifuged for 10 minutes at four degrees Celsius at 3500rpm. Afterwards the centrifuged plasma will be transferred into aliquots and stored at -80 degrees Celsius until analyzed.

CONDUCT OF THE STUDY

This study will require the participants to attend four clinic sessions on four separate days.

Clinic 1(day 0): Participants are expected to complete a consent form and screening test questionnaire after which their weight, height and waist circumference are to be measured. Afterwards, approximately 0.5ml of blood will be collected by finger prick and put in a heparin tube to avoid clotting for vitamin D status screening to ascertain if participant is eligible to partake in the study. Eligible participants will be invited to take part in the study.

Clinic 2 (week 0): Weight, height, waist circumference and blood pressure and body fat measurements will be performed. Afterwards, 25ml of blood will be collected to assess the cardiometabolic risk markers. Participants will then be randomised to receive either vitamin D or placebo (without the active ingredient) supplements for the intervention period.

Clinic 3 (week 4): The procedure performed in clinic 2 will be repeated in this clinic.

Clinic 4 (Week 8): The procedure performed in clinic 2 will be repeated. It is anticipated that the maximum length of each clinic visit will be 45mins.

Participants will be expected to complete a three-day food diary and physical activity questionnaire at Clinic 2 and 4.

SAMPLE-SIZE ESTIMATION

The estimated sample size will be 58 (29 per group), this sample size will allow for the detection of a treatment difference at 95% power, 0.97 effect size and 5% significance. The power calculation was based on a study by (Witham et al., 2012), and the primary outcome flow mediated dilation (FMD) a parameter of endothelial function from which an estimate of 29 per group was obtained, to allow for loss to follow up, sample size was increased to 37 (25%) per group (n= 74). Sample size estimation was conducted using G. Power version 3.1 software.

DATA-ANALYSIS

Data will be checked for a normal distribution by using Shapiro-Wilk since n = 74, and a homogenous variance will be assessed by Levene's statistic. if assumptions of a normal distribution and homogenous variance have been met , a parametric approach will be adopted,if not, a non parametric approach will be adopted

To assess the difference between the groups and the repeated measurement, i will perform a Mixed Model Anova,and any difference observed will be further analysed by a post- hoc, Tukey test.

To check for a relationship between variables and 25(OH)D, Pearson's correlation will be conducted if assumptions were met or spearman's correlation if assumptions were not met .

Descriptive statistics will be consulted to determine where findings differ from baseline values.The mean and standard deviation will provide information about changes that will occur.

Eligibility criteria: Inclusion Criteria:

* Healthy males aged 18-65 years,
* Those with a BMI ≥ 25kg/m2
* Those with plasma 25(OH)D concentrations \< 75nmol/l

Exclusion Criteria:

* Those with gastrointestinal disease, cardiovascular disease, diabetes, osteoporosis, renal and hepatic disorders
* Those taking weight loss drugs
* Those taking cholesterol lowering drugs
* Those currently on a weight reduction programme
* Those with blood pressure ≥ 160/90 mm Hg
* Those taking vitamin D/calcium supplements

Primary outcomes:
measure: Pulsewave Velocity
timeFrame: 0,4 and 8 weeks
Secondary outcomes:
measure: Aix Brachial
timeFrame: 0,4 and 8 weeks
measure: Aix Aortic
timeFrame: 0,4 and 8 weeks
measure: Mean Arterial Pressure
timeFrame: 0,4 and 8 weeks
measure: Pulse Pressure
timeFrame: 0,4 and 8 weeks
measure: Systolic Blood Pressure
timeFrame: 0,4 and 8 weeks
Other outcomes:
measure: Diastolic Blood Pressure
timeFrame: 0,4 and 8 weeks
measure: E-selectin
timeFrame: 0,4 and 8 weeks
measure: LDL Cholesterol
timeFrame: 0,4 and 8 weeks
measure: HDL Cholesterol
timeFrame: 0,4 and 8 weeks
measure: Total Cholesterol
timeFrame: 0,4 and 8 weeks
measure: Triacylglycerols
timeFrame: 0,4 and 8 weeks
measure: Plasma Isoprostanes
timeFrame: 0,4 and 8 weeks
measure: Plasma Renin
timeFrame: 0,4 and 8 weeks
measure: Plasma C-Reactive Protein (CRP)
timeFrame: 0,4 and 8 weeks
measure: Plasma Glucose
timeFrame: 0,4 and 8 weeks
measure: Plasma Insulin
timeFrame: 0,4 and 8 weeks
measure: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: 0,4 and 8 weeks
measure: Plasma 25(OH)D
timeFrame: 0,4 and 8 weeks
measure: Plasma Parathyroid Hormone (PTH)
timeFrame: 0,4 and 8 weeks
measure: Plasma Osteocalcin
timeFrame: 0,4 and 8 weeks
measure: Plasma Aldosterone
timeFrame: 0,4 and 8 weeks
measure: Plasma Angiotensin II
timeFrame: 0,4 and 8 weeks
Locations:
city: Chester
country: United Kingdom
facility: University of Chester
Study officials:
affiliation: University of Chester
name: Sohail Mushtaq, PhD
role: PRINCIPAL_INVESTIGATOR
References: