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

Allergy Clinical Trial

— NEMAU  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05758532
• Other study ID #: 2022-00616
• Secondary ID: Ambizione n° PZ0
• Status: Recruiting
• Phase: Phase 4
• Start date: March 17, 2023
• Est. completion date: December 2026

Study information

• Verified date: May 2024
• Source: Pediatric Clinical Research Platform
• Contact: Laure F Pittet, MD-PhD
• Phone: +41 22 372 33 11
• Email: laure.pittet[@]hcuge.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 6 Months

Eligibility

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)

Related Conditions & MeSH terms

• Allergy
• Communicable Diseases
• Eczema
• Hypersensitivity
• Infections
• Respiratory Tract Infections

Intervention

Biological:
• Measles-Mumps-Rubella vaccine (MMR)
0.5 ml of MMR vaccine injected intramuscularly in the deltoid region or in the anterolateral area of the thigh

Locations

Country	Name	City	State
Switzerland	University Hospitals of Geneva	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
Laure Pittet, MD-PhD

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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