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| ID | Type | Description | Link |
|---|---|---|---|
| Ambizione n° PZ00P3_209050 | Other Grant/Funding Number | Swiss National Science Foundation | |
| STARTER-MD n° RS08-08 | Other Grant/Funding Number | Foundation Louis-Jeantet and Private Foundation of the HUG | |
| PRD n° 4-2022-I | Other Grant/Funding Number | University Hospitals of Geneva |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| C.C. : Both MMR doses given on current schedule (9 months and 12 months) | Active Comparator | Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at:
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| M.C. : 1st MMR on modified schedule (6 months) and 2nd MMR on current schedule (12 months) | Experimental | Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at:
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| C. M. : 1st MMR on current schedule (9 months) and 2nd MMR on modified schedule (13 months) | Experimental | Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at:
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| M.M. : Both MMR doses given on modified schedule (6 months and 13 months) | Experimental | Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Measles-Mumps-Rubella vaccine (MMR) | Biological | 0.5 ml of MMR vaccine injected intramuscularly in the deltoid region or in the anterolateral area of the thigh |
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| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Allergic/atopic diseases: time to first allergic/atopic disease flare within the 3 months following randomisation | Calculated as: For participants who have a flare: Date of event onset - date of randomisation For participants who did not have a flare: Earliest censoring date - date of randomisation | Measured over the 3 months following randomisation |
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
Exclusion Criteria:
Contra-indications to MMR, including
Vaccine refusal
Indication for an early MMR vaccination, including
Indication for vaccination with MMR-varicella (MMRV) instead of MMR, including
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)
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Laure F Pittet, MD-PhD | Contact | +41 22 372 33 11 | laure.pittet@hcuge.ch |
| Name | Affiliation | Role |
|---|---|---|
| Laure F Pittet, MD-PhD | University Hospitals of Geneva | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals of Geneva | Recruiting | Geneva | 1211 | Switzerland |
Under the terms of the funding agreement with the Swiss National Science Foundation, the NEMAU trial has a data sharing agreement in place.
An anonymised Individual Participant Data (IPD) dataset and a data dictionary will be provided to a FAIR platform after database lock.
After database lock, a 12-month embargo period will be in place, to allow adequate time for analyses and publication outputs. Data transfer to a FAIR plateform will occur during the embargo period.
Researchers from a recognised research institution can approach the PI for access of data.
The researcher will need to provide evidence that the proposed use of the data has been ethically reviewed and approved by an Institutional Review Board (IRB)/ Human Research Ethics Committee(HREC), and accept HUG's conditions, under a collaborator agreement.
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Phase IV, single-centre, 4-group, open-label, randomised controlled trial with a factorial design (primary outcome analysed as a 2-group trial)
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| 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 |
| Allergic/atopic diseases: time to first allergic/atopic disease flare within the 18 months following randomisation | Calculated as: For participants who have a flare: Date of event onset - date of randomisation For participants who did not have a flare: Earliest censoring date - date of randomisation | Measured over the 18 months following randomisation |
| Allergic/atopic diseases: Prevalence of allergic/atopic disease within the 3 months following randomisation | Calculated as: number of participants who have a flare / total number of participants | Measured over the 3 months following randomisation |
| Allergic/atopic diseases: Prevalence of allergic/atopic disease within the 18 months following randomisation | Calculated as: number of participants who have a flare / total number of participants | Measured over the 18 months following randomisation |
| Allergic/atopic diseases: Incidence of allergic/atopic disease flare within the 3 months following randomisation | Calculated as: number of flares / total time of follow-up | Measured over the 3 months following randomisation |
| Allergic/atopic diseases: Incidence of allergic/atopic disease flare within the 18 months following randomisation | Calculated as: number of flares / total time of follow-up | Measured over the 18 months following randomisation |
| Allergic/atopic diseases: Days free of allergic/atopic disease flare within the 3 months following randomisation | Calculated as: number of days free of flare / total days of follow-up of participants | Measured over the 3 months following randomisation |
| Allergic/atopic diseases: Days free of allergic/atopic disease flare within the 18 months following randomisation | Calculated as: number of days free of flare / total days of follow-up of participants | Measured over the 18 months following randomisation |
| Eczema severity: Difference in eczema severity as assessed by SCORAD at 3 months following randomisation | Calculated as the difference in SCORAD score | Measured at 3 months after randomisation |
| Eczema severity: Difference in eczema severity as assessed by SCORAD at 18 months following randomisation | Calculated as the difference in SCORAD score | Measured at 18 months after randomisation |
| Eczema severity: Difference in eczema severity as assessed by POEM at 3 months following randomisation | Calculated as the difference in POEM score | Measured at 3 months after randomisation |
| Eczema severity: Difference in eczema severity as assessed by POEM at 18 months following randomisation | Calculated as the difference in POEM score | Measured at 18 months after randomisation |
| Eczema severity: Difference in eczema impact on quality of life at 3 months following randomisation | Assessed by IDQOL score | Measured at 3 months after randomisation |
| Eczema severity: Difference in eczema impact on quality of life at 18 months following randomisation | Assessed by IDQOL score | Measured at 18 months after randomisation |
| Eczema severity: Topical steroid use for eczema within 3 months following randomisation | Per event, defined as a binary variable (yes/no) | Measured over the 3 months following randomisation |
| Eczema severity: Topical steroid use for eczema within the 18 months following randomisation | Per event, defined as a binary variable (yes/no) | Measured over the 18 months following randomisation |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D006967 | Hypersensitivity |
| D004485 | Eczema |
| ID | Term |
|---|---|
| D012140 | Respiratory Tract Diseases |
| D007154 | Immune System Diseases |
| D003872 | Dermatitis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
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| ID | Term |
|---|---|
| D022542 | Measles-Mumps-Rubella Vaccine |
| ID | Term |
|---|---|
| D017778 | Vaccines, Combined |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D008458 | Measles Vaccine |
| D014765 | Viral Vaccines |
| D009108 | Mumps Vaccine |
| D012411 | Rubella Vaccine |
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