BCG-induced Epigenetic Modifications in the NEXT Generation

Phase 4

Active, not recruiting

• Conditions: BCG Vaccine; Trained Immunity; Epigenetics
• Interventions: Biological: BCG-Vaccine SSI [Statens Serum Institut]) Danish strain 1331; Biological: Placebo

• Registration Number: NCT05766345
• Lead Sponsor: Radboud University Medical Center

Brief Summary

Non-specific protective effects resulting from the BCG vaccine appear to be paternally inheritable. Since the BCG vaccine is known to induce trained immunity, epigenetics might explain the fathers' contribution to the immune profile of their offspring. Epigenetic inheritance in mice has recently been demonstrated, but is not established in humans yet. By studying the DNA methylation profile of sperm cells after BCG vaccination, we aim to gain insight into the possibility of epigenetic inheritance in human males.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-16
• Study First Submitted QC: 2023-03-02
• Study First Posted: 2023-03-13
• Study Start: 2023-10-02
• Status Verified: 2024-02
• Last Update Submitted: 2024-04-09
• Last Update Posted: 2024-04-10
• Primary Completion: 2024-08
• Study Completion: 2024-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 36

Inclusion Criteria

• Healthy
• Male
• Age 18-25 years (at the moment of trial start)

Exclusion Criteria

• Any systemic disease or conditin, or the use of systemic medication (with the exception of non-threatening alelrgies, e.g. hay fever)
• Smoking or drug use
• Prior BCG vaccination
• Other vaccination four weeks prior to trial start or four weeks after the first study visit (no vaccine in the same arm as the BCG vaccine for three months)
• Acute illness two weeks prior to trial start
• Known allergy or history of anaphylaxis/other serious adverse reaction to any vaccine
• Participation in another drug trial
• Legally incapacitated or unwilling to provide informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BCG vaccine	BCG-Vaccine SSI [Statens Serum Institut]) Danish strain 1331	BCG-Vaccine SSI \[Statens Serum Institut\]) Danish strain 1331 0.1ml (=0.0075mg) One-time vaccination intradermally
Placebo vaccine	Placebo	0.9% NaCl placebo 0.1ml One-time vaccination intradermally

Primary Outcome Measures

Name	Time	Method
DNA methylation profile of sperm cells (first comparison; CHANGE)	Comparing T3 to baseline	Differentially methylated regions (DMRs)
DNA methylation profile of sperm cells (second comparison; CHANGE)	Comparing T4 to baseline	Differentially methylated regions (DMRs)

Secondary Outcome Measures

Name	Time	Method
Immunological profile of PBMCs, before and after BCG vaccination (comparison; CHANGE)	Comparing T1-T4 to baseline	Cytokine production assays (e.g. TNFa, IL6, IL1b)
CHANGE of the epigenetic profile of innate immune cells	Comparing T1-T4 to baseline	Differentially methylated regions (DMRs), ATAC sequencing, RNA sequencing

Trial Locations

Locations (1)

Radboudumc; 🇳🇱 Nijmegen, Netherlands