Effects Vitamin D Suppletion on Postprandial Leukocyte Activation (DOSFEM)

Effects of High and Low Dose Vitamin D Suppletion on Postprandial Leukocyte Activation, Oxidative Stress and Vascular Function in Healthy Overweight and Obese Females

Administration of vitamin D will have a beneficial effect on postprandial leukocyte activation, oxidative stress and arterial stiffness in vitamin D deficient females. High doses of vitamin D may have a more pronounced effect than low doses.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Oxidative Stress; Leukocyte Activation Disorder
• Intervention / Treatment: Drug: Cholecalciferol; Drug: Cholecalciferol

Detailed Description

Rationale: Postprandial lipemia, known to be associated with acute leukocyte activation, impairs endothelial function and promotes atherosclerosis. Deficiency of vitamin D is associated with increased cardiovascular risk, but the precise mechanism is still unclear. A recent pilot study performed in our laboratory showed improved postprandial vascular function by pulse wave analysis and decreased postprandial leukocyte activation after vitamin D supplementation. Interestingly, the effects on leukocyte activation were solely found in females.

Hypothesis: The beneficial effects of vitamin D administration on postprandial leukocyte activation are mediated by suppression of oxidative stress. High doses of vitamin D may have a more pronounced effect than low doses.

Objective: To estimate the effect sizes of different doses of vitamin D on postprandial leukocyte activation markers, oxidative stress and arterial stiffness in vitamin D deficient females.

Study design: Randomized, double blind pilot study. Study population: Premenopausal overweight and obese female volunteers with proven vitamin D deficiency, ≥ 18 years of age.

Intervention: Two oral fat load tests (OFLTs) will be performed. After the first OFLT, volunteers will be randomly assigned to receive a single low dose (75 000 IU) or high dose (300 000 IU) of cholecalciferol drink. One week later the OFLT will be repeated.

Main study parameters/endpoints: Postprandial leukocyte activation, oxidative stress parameters and arterial augmentation index.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The use of a single dose of 300 000 IU of cholecalciferol has been established to be a safe and effective way to correct vitamin D deficiency. Volunteers will be hospitalized on 2 different days (day 1, day 8) for approximately nine hours each day and receive an oral fat load. Cholecalciferol will be administered once. Volunteers will be instructed not to take vitamin D supplements during the study up until 3 months after the study. The volunteers' general practitioner will be informed on their participation. A total of 222ml (111ml for each postprandial test) of blood will be drawn. Volunteers will be allowed to drink only water during the tests. There is a theoretical risk of hypercalcemia but no excessive risk is involved. Volunteers receive 250 euros for full participation. Furthermore, volunteers will be told and given advice if they turn out to suffer from hyperlipidemia or any other condition.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3045 PM
      • Sint Franciscus Gasthuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age of 18 years or older;
• Pre-menopausal;
• BMI ≥25.0 kg/m2;
• Vitamin D deficiency, defined by a 25-hydroxyvitamin D level of <30ng/ml;
• Use of oral contraceptives.

Exclusion Criteria:

• The use of any kind of medication except oral contraceptives;
• Smoking;
• Pregnancy;
• Participation in a clinical study less than 6 months before inclusion;
• The use of (multi)vitamin supplements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High dose vitamin D; Volunteers assigned to this arm will receive a single dose of oral cholecalciferol 300 000 IU, in the form of 3 ml D-cura drink 100 000 IU/ml	Drug: Cholecalciferol; Single dose D-cura cholecalciferol drink 100 000 IU/ml, in total 300 000 IU (=3ml); Other Names: D-cura; Drug: Cholecalciferol; Single dose D-cura cholecalciferol drink 250 000 IU/ml, in total 75 000 IU (=3ml); Other Names: D-cura
Active Comparator: Low dose vitamin D; Volunteers assigned to this arm will receive a single dose of oral cholecalciferol 75000 IU, in the form of 3 ml D-cura drink 25 000 IU/ml	Drug: Cholecalciferol; Single dose D-cura cholecalciferol drink 100 000 IU/ml, in total 300 000 IU (=3ml); Other Names: D-cura; Drug: Cholecalciferol; Single dose D-cura cholecalciferol drink 250 000 IU/ml, in total 75 000 IU (=3ml); Other Names: D-cura

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of vitamin D on leukocyte cluster of differentiation antigen 11b expression	the differential effect of 75 000 IU low dose vs. 300 000 IU high dose vitamin D on postprandial leukocyte activation markers cluster of differentiation antigen 11b	2, 4, 6 and 8 hours postprandial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of vitamin D on oxidative stress	the differential effect of 75 000 IU low dose vs. 300 000 IU high dose vitamin D on oxidative stress	2,4,6 and 8 hours postprandial
Effect of vitamin D on vascular function	the differential effect of 75 000 IU low dose vs. 300 000 IU high dose vitamin D on vascular function (Pulse Wave Velocity and Augmentation Index)	0,2,6,8 and 8 hours postprandial

Collaborators and Investigators

• Sponsor: Sint Franciscus Gasthuis
• Investigators: Study Chair: Manuel Castro Cabezas, MD, PhD, Sint Franciscus Gasthuis

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: October 17, 2013
• First Submitted That Met QC Criteria: October 17, 2013
• First Posted (Estimate): October 23, 2013

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: October 4, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: NL44804.101.13