Clinical trial NCT05758532: Non-specific Effects of a Modified Measles Vaccination Schedule to Prevent Allergy and Unrelated Infection in Children
Official title: Harnessing the Beneficial Non-specific Effects of Measles-mumps-rubella Vaccine in Children on Infection With Unrelated Pathogens and Allergic Diseases - a Single-centre Phase IV RCT With a Factorial Design
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Respiratory Tract Infections
Infections
Allergy
Eczema
Keywords: Non-specific/off-target effect of vaccine
Lead sponsor: Pediatric Clinical Research Platform
Sponsor class: OTHER
First posted: 2023-03-07
Enrollment: 500
Sex: ALL
Minimum age (years): 6
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Phase IV, single-centre, 4-group, open-label, randomised controlled trial with a factorial design (primary outcome analysed as a 2-group trial)
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of respiratory infection within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
Secondary outcomes:
measure: Infection: Time to first infection within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Infection: Time to first infection within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Infection: Prevalence of infection within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Infection: Prevalence of infection within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Infection: Incidence of infection within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Infection: Incidence of infection within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Infection: Number of days free of infection within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Infection: Number of days free of infection within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Infection severity: Duration of infection within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Infection severity: Duration of infection within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Infection severity: Antibiotic use for infection within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Infection severity: Antibiotic use for infection within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Infection severity: Hospitalisation for infection within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Infection severity: Hospitalisation for infection within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Infection severity: Outcome of infection within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Infection severity: Outcome of infection within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Incidence of respiratory infection within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
Other outcomes:
measure: Allergic/atopic diseases: time to first allergic/atopic disease flare within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Allergic/atopic diseases: time to first allergic/atopic disease flare within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Allergic/atopic diseases: Prevalence of allergic/atopic disease within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Allergic/atopic diseases: Prevalence of allergic/atopic disease within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Allergic/atopic diseases: Incidence of allergic/atopic disease flare within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Allergic/atopic diseases: Incidence of allergic/atopic disease flare within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Allergic/atopic diseases: Days free of allergic/atopic disease flare within the 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Allergic/atopic diseases: Days free of allergic/atopic disease flare within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
measure: Eczema severity: Difference in eczema severity as assessed by SCORAD at 3 months following randomisation
timeFrame: Measured at 3 months after randomisation
measure: Eczema severity: Difference in eczema severity as assessed by SCORAD at 18 months following randomisation
timeFrame: Measured at 18 months after randomisation
measure: Eczema severity: Difference in eczema severity as assessed by POEM at 3 months following randomisation
timeFrame: Measured at 3 months after randomisation
measure: Eczema severity: Difference in eczema severity as assessed by POEM at 18 months following randomisation
timeFrame: Measured at 18 months after randomisation
measure: Eczema severity: Difference in eczema impact on quality of life at 3 months following randomisation
timeFrame: Measured at 3 months after randomisation
measure: Eczema severity: Difference in eczema impact on quality of life at 18 months following randomisation
timeFrame: Measured at 18 months after randomisation
measure: Eczema severity: Topical steroid use for eczema within 3 months following randomisation
timeFrame: Measured over the 3 months following randomisation
measure: Eczema severity: Topical steroid use for eczema within the 18 months following randomisation
timeFrame: Measured over the 18 months following randomisation
Locations:
city: Geneva
country: Switzerland
facility: University Hospitals of Geneva
Study officials:
affiliation: University Hospitals of Geneva
name: Laure F Pittet, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: