VitDPAS: Epigenetic Memory of Vitamin D Supplementation

Sponsor

Polish Academy of Sciences (Other)

Overall Status

Recruiting

CT.gov ID

NCT06104111

Collaborator

(none)

Enrollment

Location

Arm

17.9

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators will study the mechanistic details of dietary programming of the epigenome at the example of epigenetic programming of primary human immune cells with the micronutrient vitamin D3. They will follow a small number of healthy adult volunteers individually over time while measuring per individual a large number of molecular and dynamic parameters that will be used for mechanistic modeling. The main hypothesis of the investigators is that nutritional components, such as vitamin D3, have a direct effect on the epigenome of the different cell types of the immune system. Using complementary in vivo, in vitro and in silico approaches, they will investigate the mechanistic basis of this dietary epigenetic programming process and how it creates memory.

Condition or Disease	Intervention/Treatment	Phase
Immune System Diseases Infections Healthy Lifestyle	Dietary Supplement: Vitamin D3	Phase 1

Detailed Description

Exposure to dietary molecules during adulthood creates an epigenetic memory in immune cells affecting disease risk in later years of life. Many nutritional molecules have a direct effect on the human genome and/or epigenome, since they (or their metabolites) activate transcription factors or chromatin modifiers. This process is the mechanistic basis of the discipline nutrigenomics. Thus, the daily diet of humans leads to changes in the transcriptome and epigenome of many tissues and cell types. In this way, many physiological functions of the human body, such as a well-responding immune system, are influenced by diet. Some of these effects are not only transient but may lead to persistent changes of the epigenome in many different tissues. However, the mechanistic details of this dietary programming of the epigenome are not well understood. Therefore, in this study, the investigators will study this process at the example of epigenetic programming of primary human immune cells with the micronutrient vitamin D3. They will use the approach to follow a small but sufficient number of healthy adult volunteers (based on power calculation of self-controlled longitudinal studies) individually over time while measuring per individual a large number of molecular and dynamic parameters that will be used for mechanistic modeling, instead of investigating only few parameters from a large number of participants for statistical modeling. The main hypothesis of the investigators is that nutritional components, such as vitamin D3, have a direct effect on the epigenome of the different cell types of the immune system. Using complementary in vivo, in vitro and in silico approaches, they will investigate the mechanistic basis of this dietary epigenetic programming process and how it creates memory.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Investigating the Mechanisms of Epigenetic Memory at the Example of the Responsiveness of Human Immune Cells to Vitamin D

Actual Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Feb 14, 2024

Anticipated Study Completion Date :

Mar 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin D3 (cholecalciferol) 1000 IU vitamin D3 (cholecalciferol)/kg body mass will be taken in form of individual number of pills (4000 IU each, e.g. 20 pills for a person of 80 kg) in the morning together with a breakfast at days 0, 28 and 56	Dietary Supplement: Vitamin D3 Vitamin D3 bolus at days 0, 28 and 56. Blood samples taken at days 0, 1, 28, 29, 56, 57 ad 84 Other Names: Cholecalciferol

Arm

Intervention/Treatment

Experimental: Vitamin D3 (cholecalciferol)

1000 IU vitamin D3 (cholecalciferol)/kg body mass will be taken in form of individual number of pills (4000 IU each, e.g. 20 pills for a person of 80 kg) in the morning together with a breakfast at days 0, 28 and 56

Dietary Supplement: Vitamin D3

Vitamin D3 bolus at days 0, 28 and 56. Blood samples taken at days 0, 1, 28, 29, 56, 57 ad 84

Other Names:

Cholecalciferol

Outcome Measures

Primary Outcome Measures

Vitamin D-induced changes in the epigenome of PBMCs describing the individual -specific vitamin D response index of the study participants [3 months]
A bolus of vitamin D3 (monthly dose, taken once a month in three repeats) will change the epigenome (and transcriptome) of PBMCs of the study participants in an individual-specific way. These measurements will allow to distinguish the molecular response of the study participants, in order to segregate them into high, mid and low responders to vitamin D. This classification will lead to individual-specific recommendations for daily vitamin D3 supplementation in following winters. Moreover, the molecular investigations will allow a better understanding of the molecular mechanisms of vitamin D responsiveness

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

-Healthy adult (18-65 years)

Exclusion Criteria:

Smoker
BMI > 28 kg/m2
History of kidney stones, renal failure or dialysis, hypercalcemia, hypo- or hyperparathyroidism, severe liver disease (cirrhosis), or sarcoidosis or other granulomatous diseases, such as active chronic tuberculosis or Wegener's granulomatosis