Clinical trial NCT05995522: Effect of Vitamin K2 Over Osteocalcin, Leptin, Cytokines, and Cardiovascular Risk in Young Adults With Overweight and Obesity
Official title: Effect of Vitamin K2 Supplementation and Its Association With Osteocalcin Serum Levels, Leptin, Th1/Th2 Cytokine Profile, and Cardiovascular Risk in Young Mexican Adults With Overweight and Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Overweight and Obesity
Cardiometabolic Risk Factors
Keywords: Vitamin K
Overweight and Obesity
Cardiometabolic Risk Factors
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
First posted: 2023-08-16
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Clinical trial parallel design. Two groups with intervention, one with supplementation and other with placebo
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to compare de effect of vitamin K2 in young adults with overweight or obesity. The main questions to answer are:

What is the effect of Vitamin K2 supplementation on methylation, serum concentration of ucOC, cOC, Gas6, leptin, inflammatory markers, cardiometabolic risk factors, and cardiovascular risk in overweight or obese young adults? Participants will be assigned to one of two intervention groups where they will consume Vitamin K2 100 µg per day or cornstarch 500 mg per day for 90 days.

If there is a comparison group: Investigators will compare the supplementation group (Vitamin K2) with the placebo group (cornstarch) to see if vitamin K2 supplementation modifies methylation, increases serum vitamin K, osteocalcin, growth arrest-specific 6 protein serum concentration, decreases serum leptin concentration, inflammatory markers and reduces cardiometabolic risk factors and cardiovascular risk.

Detailed description: Study Overview To meet the objectives of the project, two groups will be compared, one that will be supplemented with vitamin K and another of patients who will receive corn starch as a placebo. Patients are going to have a follow up during 3 months with periodic evaluations every 30 days.

This is a double-blind study, it is achieved by maintaining similarities in appearance, taste and smell between the treatments that will be delivered in the same vials, with same number of pills and identical in shape, color and consistency for each study group.

Patient recruitment will take place by disseminating information through physical and social media, once potential participants have been identified, they will be contacted and informed about the project, and if they decide to participate in the study, they will be asked to sign the informed consent.

Simple randomization will be performed using R software to assign participants to one of the study groups. A clinical history, anthropometric measurements and blood sampling shall be applied.

Nutritional recommendations based on the position of the Academy of Nutrition and Dietetics for the treatment of overweight and obesity and the healthy eating plate of Harvard University will be given. An appointment is to be scheduled every 30 days in order to provide the supplementation and follow-up. At the end, the pertinent statistical analyzes will be carried out.

Notification of adverse effects will be made in each of the sessions, in addition to this the participants will have the contact of the researchers to notify any anomaly.

Sample's size calculation

The sample size was calculated using the statistical formula for the comparison of two means. This estimate was made using the following formula:

n=2(Zα+Z\[1-β\]2xSD2/d2

Where:

n= sample size required in each group SD= standard deviation of the effect Zα: to the value of Z for a confidence level of 95% Z\[1-β}: to the value of Z for a statistical power of 80% D= effect size A total of 19.72 patients per group were obtained. Considering a 20% loss, 24 patients are needed per study group.

Ethical considerations The study was approved by the Biosafety committee, research ethics committee and research committee of the University Center for Health Sciences, University of Guadalajara: CI-00421. The committees of the University have the authority to monitor and audit the study at any of its stages once it has been approved.

Objetives General objective Evaluate the effect of vitamin K2 supplementation on methylation, the serum concentration of total vitamin K, osteocalcin, growth arrest-specific 6 protein, leptin, inflammatory markers, cardiometabolic risk factors and cardiovascular risk in young Mexican adults with overweight or obesity.

Specific objectives

1. Compare the baseline variables between groups.
2. Compare the variable changes across the time within groups
3. Compare the variable changes across the time between groups

Statistical analysis The Shapiro-Wilk normality test is performed to determine whether the analysis will require parametric or non-parametric tests. Qualitative variables will be expressed as frequencies and percentages, while quantitative variables will be expressed as mean and standard deviation in parametric data or medians and ranges in non-parametric data.

Specific objective 1 Statistical technique T-student for independent samples if it has a normal distribution or by U-Mann Whitney for independent samples if it does not have a normal distribution

Specific objective 2 Variables with two measures Statistical technique T-student for paired samples if it has a normal distribution or the Wilcoxon signed-rank test if it does not have a normal distribution

Variables with more than two measures Statistical technique Repeated measures ANOVA if it has a normal distribution or the Friedman Test if it does not have a normal distribution

Specific objective 3 Statistical technique The effect size of the groups is compared with T-student for independent samples if it has a normal distribution or by U-Mann Whitney for independent samples if it does not have a normal distribution

Eligibility criteria: Inclusion Criteria:

* Body Mass Index greater than 25 kg/m2 and less than 40 kg/m2
* That they agree to participate in the study voluntarily and informed and sign the informed consent

Exclusion Criteria:

* People with self-reported diagnosis of chronic kidney, gastrointestinal or systemic disease
* Use of bile acid sequestrants drugs, insulin, glucocorticoids, contraceptives, bisphosphonates, thiazides, levetiracetam, thiazolidinediones, anticoagulants or estrogenic drugs and vitamin D, vitamin K, vitamin A, vitamin E, omegas or calcium supplements
* Patients who are on a hypocaloric or low-fat diet
* Self-reported pregnancy

Primary outcomes:
measure: Osteocalcin serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Vitamin K serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Leptin serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Tumour Necrosis Factor alpha serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Interleukin-1 Beta serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Interleukin-6 serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Interleukin-4 serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Interleukin-10 serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Cardiovascular risk
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: LEP gene methylation
timeFrame: Baseline and after 90 days of intervention
Secondary outcomes:
measure: Growth arrest-specific 6 protein serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Global methylation
timeFrame: Baseline and after 90 days of intervention
measure: Atherogenic indices
timeFrame: Baseline and after 90 days of intervention
measure: Triglycerides serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Total cholesterol serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: HDL cholesterol serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: LDL cholesterol serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: VLDL cholesterol serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Glucose serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Blood pressure
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Insulin serum concentration
timeFrame: Baseline and after 90 days of intervention
measure: Weight
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Body mass index
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Waist circumference
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Hip circumference
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Fat mass
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: % fat
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Lean mass
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Estimated energy consumption
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Estimated protein consumption
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Estimated carbohydrates consumption
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Estimated fat consumption
timeFrame: Baseline, after 30, 60 and 90 days of intervention
measure: Estimated vitamin K consumption
timeFrame: Baseline, after 30, 60 and 90 days of intervention
Other outcomes:
Locations:
city: Guadalajara
country: Mexico
facility: University of Guadalajara
state: Jalisco
Study officials:
name: Andrés López Quintero, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aguayo-Ruiz JI, Garcia-Cobian TA, Pascoe-Gonzalez S, Sanchez-Enriquez S, Llamas-Covarrubias IM, Garcia-Iglesias T, Lopez-Quintero A, Llamas-Covarrubias MA, Trujillo-Quiroz J, Rivera-Leon EA. Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: a randomized, double-blind, clinical trial. Diabetol Metab Syndr. 2020 Aug 18;12:73. doi: 10.1186/s13098-020-00580-w. eCollection 2020.