Non-specific Effects of a Modified Measles Vaccination Schedule to Prevent Allergy and Unrelated Infection in Children

Phase 4

Recruiting

• Conditions: Allergy; Respiratory Tract Infections; Eczema; Infections
• Interventions: Biological: Measles-Mumps-Rubella vaccine (MMR)

• Registration Number: NCT05758532
• Lead Sponsor: Laure Pittet, MD-PhD

Brief Summary

The goal of this clinical trial is to evaluate the off-target/non-specific effects of the measles-mumps-rubella (MMR) vaccine in children.

Detailed Description

The overall objective of this project is to assess, in a randomised control trial (RCT), the effects of a "modified" MMR schedule in children, by an in-depth characterisation of both the clinical effects and the underlying immunomodulatory changes.

The current Swiss administration schedule of giving MMR at 9 and 12 months of age ("current schedule") will be compared with a "modified schedule". This is expected to maximise the beneficial non-specific effects of MMR by giving it at 6 and 13 months of age, separately from other vaccines ("modified schedule"). Factorial analysis will enable assessment of the benefit of the intervention on each of the two doses of MMR separately or in combination.

The clinical aims are to determine whether a modified schedule of MMR administration reduces both the risk and severity of: (i) infections with unrelated pathogens and (ii) atopic and allergic diseases.

The laboratory aims are to: (i) quantify and characterise the immunological non-specific effects of MMR, and (ii) identify the biological pathways and molecular mechanisms that are altered by MMR vaccination.

Study Timeline

• Study First Submitted: 2023-02-10
• Study First Submitted QC: 2023-02-24
• Study First Posted: 2023-03-07
• Study Start: 2023-03-17
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-27
• Last Update Posted: 2024-05-29
• Primary Completion: 2026-04
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

1. Informed Consent as documented by signature

2. 6-month-old children

3. In overall good health, without any clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.) and no clinically significant abnormal finding on history and/or physical examination

4. Fully immunised for age according to the Swiss vaccination schedule

   1. with at least 2 doses of DTP-containing vaccine
   2. the last dose of vaccine received at least 2 weeks prior to enrolment

Exclusion Criteria

1. Contra-indications to MMR, including

   1. immunosuppression (i.e. proven, suspected, or planned)
   2. allergy to a component of the vaccine
   3. receipt of a live-attenuated vaccine in the four weeks prior to inclusion

2. Vaccine refusal

3. Indication for an early MMR vaccination, including

   1. Measles outbreak
   2. Planned immunosuppression (indication to an accelerated schedule to be completed before starting an immunosuppressive treatment)
   3. Travel to a region with a high risk of measles outbreak

4. Indication for vaccination with MMR-varicella (MMRV) instead of MMR, including

   1. severe eczema
   2. parental will

5. Parental inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, known/suspected non-compliance, substance abuse, etc.

6. Plan to move out of the country or have prolong absence during the trial

7. Other sibling included in the trial (in the case of multiple pregnancy, only one child can be randomised)

8. Any temporary contra-indication to MMR, including child being sick (active significant illness, inclusion can be delayed a few days until the illness resolves)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
M.M. : Both MMR doses given on modified schedule (6 months and 13 months)	Measles-Mumps-Rubella vaccine (MMR)	Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: * 6 months (= modified schedule) * 13 months, distant from other vaccines (= modified schedule)
C.C. : Both MMR doses given on current schedule (9 months and 12 months)	Measles-Mumps-Rubella vaccine (MMR)	Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: * 9 months (= current Swiss schedule) * 12 months, concomitant with other vaccines (= current Swiss schedule)
M.C. : 1st MMR on modified schedule (6 months) and 2nd MMR on current schedule (12 months)	Measles-Mumps-Rubella vaccine (MMR)	Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: * 6 months (= modified schedule) * 12 months, concomitant with other vaccines (= current Swiss schedule)
C. M. : 1st MMR on current schedule (9 months) and 2nd MMR on modified schedule (13 months)	Measles-Mumps-Rubella vaccine (MMR)	Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: * 9 months (= current Swiss schedule) * 13 months, distant from other vaccines (= modified schedule)

Primary Outcome Measures

Name	Time	Method
Incidence of respiratory infection within the 3 months following randomisation	Measured over the 3 months following randomisation	Incidence of parent-reported respiratory infections between 6 months and 9 months of age using fortnightly REDCap questionnaires, with validation of data by confirmation with treating paediatrician and medical records.

Secondary Outcome Measures

Name	Time	Method
Infection: Time to first infection within the 3 months following randomisation	Measured over the 3 months following randomisation	Calculated as: For participants who have an event: Date of event onset - date of randomisation; For participants who did not have an event: Earliest censoring date - date of randomisation
Infection: Prevalence of infection within the 18 months following randomisation	Measured over the 18 months following randomisation	Calculated as: number of participants who have an event / total number of participants
Infection: Number of days free of infection within the 3 months following randomisation	Measured over the 3 months following randomisation	Calculated as: number of days free of event / total days of follow-up of participants
Infection: Number of days free of infection within the 18 months following randomisation	Measured over the 18 months following randomisation	Calculated as: number of days free of event / total days of follow-up of participants
Infection severity: Hospitalisation for infection within the 18 months following randomisation	Measured over the 18 months following randomisation	Per event, defined as a binary variable (yes/no)
Infection severity: Outcome of infection within the 18 months following randomisation	Measured over the 18 months following randomisation	Per event, defined as a categorical variable (uneventful/complication or sequel/death)
Infection severity: Duration of infection within the 3 months following randomisation	Measured over the 3 months following randomisation	Per event, calculated as: date of recovery - date of onset
Infection severity: Antibiotic use for infection within the 3 months following randomisation	Measured over the 3 months following randomisation	Per event, defined as a binary variable (yes/no)
Infection severity: Antibiotic use for infection within the 18 months following randomisation	Measured over the 18 months following randomisation	Per event, defined as a binary variable (yes/no)
Infection severity: Outcome of infection within the 3 months following randomisation	Measured over the 3 months following randomisation	Per event, defined as a categorical variable (uneventful/complication or sequel/death)
Infection: Time to first infection within the 18 months following randomisation	Measured over the 18 months following randomisation	Calculated as: For participants who have an event: Date of event onset - date of randomisation; For participants who did not have an event: Earliest censoring date - date of randomisation
Infection: Prevalence of infection within the 3 months following randomisation	Measured over the 3 months following randomisation	Calculated as: number of participants who have an event / total number of participants
Infection: Incidence of infection within the 3 months following randomisation	Measured over the 3 months following randomisation	Calculated as: number of events / total time of follow-up
Infection: Incidence of infection within the 18 months following randomisation	Measured over the 18 months following randomisation	Calculated as: number of events / total time of follow-up
Infection severity: Hospitalisation for infection within the 3 months following randomisation	Measured over the 3 months following randomisation	Per event, defined as a binary variable (yes/no)
Infection severity: Duration of infection within the 18 months following randomisation	Measured over the 18 months following randomisation	Per event, calculated as: date of recovery - date of onset
Incidence of respiratory infection within the 18 months following randomisation	Measured over the 18 months following randomisation	Incidence of parent-reported respiratory infections between 6 months and 24 months of age using fortnightly REDCap questionnaires, with validation of data by confirmation with treating paediatrician and medical records.

Trial Locations

Locations (1)

University Hospitals of Geneva; 🇨🇭 Geneva, Switzerland