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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Respiratory Tract Infections, Infections, Allergy, Eczema

Intervention / Treatment
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* Biological: Measles-Mumps-Rubella vaccine (MMR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent as documented by signature 6-month-old children 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 Fully immunised for age according to the Swiss vaccination schedule with at least 2 doses of DTP-containing vaccine the last dose of vaccine received at least 2 weeks prior to enrolment Exclusion Criteria: Contra-indications to MMR, including immunosuppression (i.e. proven, suspected, or planned) allergy to a component of the vaccine receipt of a live-attenuated vaccine in the four weeks prior to inclusion Vaccine refusal Indication for an early MMR vaccination, including Measles outbreak Planned immunosuppression (indication to an accelerated schedule to be completed before starting an immunosuppressive treatment) Travel to a region with a high risk of measles outbreak Indication for vaccination with MMR-varicella (MMRV) instead of MMR, including severe eczema parental will Parental inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, known/suspected non-compliance, substance abuse, etc. Plan to move out of the country or have prolong absence during the trial Other sibling included in the trial (in the case of multiple pregnancy, only one child can be randomised) Any temporary contra-indication to MMR, including child being sick (active significant illness, inclusion can be delayed a few days until the illness resolves)

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional 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)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: C.C. : Both MMR doses given on current schedule (9 months and 12 months)<br>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) | Biological: Measles-Mumps-Rubella vaccine (MMR)<br>* 0.5 ml of MMR vaccine injected intramuscularly in the deltoid region or in the anterolateral area of the thigh<br>|
| Experimental: M.C. : 1st MMR on modified schedule (6 months) and 2nd MMR on current schedule (12 months)<br>Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: 6 months (= modified schedule) 12 months, concomitant with other vaccines (= current Swiss schedule) | Biological: Measles-Mumps-Rubella vaccine (MMR)<br>* 0.5 ml of MMR vaccine injected intramuscularly in the deltoid region or in the anterolateral area of the thigh<br>|
| Experimental: C. M. : 1st MMR on current schedule (9 months) and 2nd MMR on modified schedule (13 months)<br>Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: 9 months (= current Swiss schedule) 13 months, distant from other vaccines (= modified schedule) | Biological: Measles-Mumps-Rubella vaccine (MMR)<br>* 0.5 ml of MMR vaccine injected intramuscularly in the deltoid region or in the anterolateral area of the thigh<br>|
| Experimental: M.M. : Both MMR doses given on modified schedule (6 months and 13 months)<br>Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: 6 months (= modified schedule) 13 months, distant from other vaccines (= modified schedule) | Biological: Measles-Mumps-Rubella vaccine (MMR)<br>* 0.5 ml of MMR vaccine injected intramuscularly in the deltoid region or in the anterolateral area of the thigh<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of respiratory infection within 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. | Measured over the 3 months following randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infection: Time to first infection within 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 | Measured over the 3 months following randomisation | 
| Infection: Time to first infection within 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 | Measured over the 18 months following randomisation | 
| Infection: Prevalence of infection within the 3 months following randomisation | Calculated as: number of participants who have an event / total number of participants | Measured over the 3 months following randomisation | 
| Infection: Prevalence of infection within the 18 months following randomisation | Calculated as: number of participants who have an event / total number of participants | Measured over the 18 months following randomisation | 
| Infection: Incidence of infection within the 3 months following randomisation | Calculated as: number of events / total time of follow-up | Measured over the 3 months following randomisation | 
| Infection: Incidence of infection within the 18 months following randomisation | Calculated as: number of events / total time of follow-up | Measured over the 18 months following randomisation | 
| Infection: Number of days free of infection within the 3 months following randomisation | Calculated as: number of days free of event / total days of follow-up of participants | Measured over the 3 months following randomisation | 
| Infection: Number of days free of infection within the 18 months following randomisation | Calculated as: number of days free of event / total days of follow-up of participants | Measured over the 18 months following randomisation | 
| Infection severity: Duration of infection within the 3 months following randomisation | Per event, calculated as: date of recovery - date of onset | Measured over the 3 months following randomisation | 
| Infection severity: Duration of infection within the 18 months following randomisation | Per event, calculated as: date of recovery - date of onset | Measured over the 18 months following randomisation | 
| Infection severity: Antibiotic use for infection within the 3 months following randomisation | Per event, defined as a binary variable (yes/no) | Measured over the 3 months following randomisation | 
| Infection severity: Antibiotic use for infection within the 18 months following randomisation | Per event, defined as a binary variable (yes/no) | Measured over the 18 months following randomisation | 
| Infection severity: Hospitalisation for infection within the 3 months following randomisation | Per event, defined as a binary variable (yes/no) | Measured over the 3 months following randomisation | 
| Infection severity: Hospitalisation for infection within the 18 months following randomisation | Per event, defined as a binary variable (yes/no) | Measured over the 18 months following randomisation | 
| Infection severity: Outcome of infection within the 3 months following randomisation | Per event, defined as a categorical variable (uneventful/complication or sequel/death) | Measured over the 3 months following randomisation | 
| Infection severity: Outcome of infection within the 18 months following randomisation | Per event, defined as a categorical variable (uneventful/complication or sequel/death) | Measured over the 18 months following randomisation | 
| Incidence of respiratory infection within 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. | Measured over the 18 months following randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-specific/off-target effect of vaccine