Allergy, Eczema, Infections, Respiratory Tract Infections
Conditions
Keywords
Non-specific/off-target effect of vaccine
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.
Interventions
BIOLOGICALMeasles-Mumps-Rubella vaccine (MMR)
0.5 ml of MMR vaccine injected intramuscularly in the deltoid region or in the anterolateral area of the thigh
Sponsors
Laure Pittet, MD-PhD
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
NONE
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)
Eligibility
Sex/Gender
ALL
Age
6 Months to 6 Months
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: 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: 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: 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: 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: 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: 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: 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: 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 |
| 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: 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 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) |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Allergic/atopic diseases: Prevalence of allergic/atopic disease within the 3 months following randomisation | Measured over the 3 months following randomisation | Calculated as: number of participants who have a flare / total number of participants |
| Allergic/atopic diseases: Prevalence of allergic/atopic disease within the 18 months following randomisation | Measured over the 18 months following randomisation | Calculated as: number of participants who have a flare / total number of participants |
| Allergic/atopic diseases: Incidence of allergic/atopic disease flare within the 3 months following randomisation | Measured over the 3 months following randomisation | Calculated as: number of flares / total time of follow-up |
| Allergic/atopic diseases: Incidence of allergic/atopic disease flare within the 18 months following randomisation | Measured over the 18 months following randomisation | Calculated as: number of flares / total time of follow-up |
| Allergic/atopic diseases: Days free of allergic/atopic disease flare within the 3 months following randomisation | Measured over the 3 months following randomisation | Calculated as: number of days free of flare / total days of follow-up of participants |
| Allergic/atopic diseases: Days free of allergic/atopic disease flare within the 18 months following randomisation | Measured over the 18 months following randomisation | Calculated as: number of days free of flare / total days of follow-up of participants |
| Eczema severity: Difference in eczema severity as assessed by SCORAD at 3 months following randomisation | Measured at 3 months after randomisation | Calculated as the difference in SCORAD score |
| Eczema severity: Difference in eczema severity as assessed by SCORAD at 18 months following randomisation | Measured at 18 months after randomisation | Calculated as the difference in SCORAD score |
| Eczema severity: Difference in eczema severity as assessed by POEM at 3 months following randomisation | Measured at 3 months after randomisation | Calculated as the difference in POEM score |
| Eczema severity: Difference in eczema severity as assessed by POEM at 18 months following randomisation | Measured at 18 months after randomisation | Calculated as the difference in POEM score |
| Eczema severity: Difference in eczema impact on quality of life at 3 months following randomisation | Measured at 3 months after randomisation | Assessed by IDQOL score |
| Eczema severity: Difference in eczema impact on quality of life at 18 months following randomisation | Measured at 18 months after randomisation | Assessed by IDQOL score |
| Eczema severity: Topical steroid use for eczema within 3 months following randomisation | Measured over the 3 months following randomisation | Per event, defined as a binary variable (yes/no) |
| Eczema severity: Topical steroid use for eczema within the 18 months following randomisation | Measured over the 18 months following randomisation | Per event, defined as a binary variable (yes/no) |
| Allergic/atopic diseases: time to first allergic/atopic disease flare within the 18 months following randomisation | Measured over 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 |
| Allergic/atopic diseases: time to first allergic/atopic disease flare within the 3 months following randomisation | Measured over 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 |
Countries
Switzerland
Contacts
Primary ContactLaure F Pittet, MD-PhD
Outcome results
None listed