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

Laure Pittet, MD-PhD

Status and phase: Enrolling; Phase 4

Conditions: Infections; Eczema; Respiratory Tract Infections; Allergy

Treatments: Biological: Measles-Mumps-Rubella vaccine (MMR)

Study type: Interventional

Funder types: Other

Identifiers

NCT05758532

Ambizione n° PZ00P3_209050 (Other Grant/Funding Number)

2022-00616

PRD n° 4-2022-I (Other Grant/Funding Number)

STARTER-MD n° RS08-08 (Other Grant/Funding Number)

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the off-target/non-specific effects of the measles-mumps-rubella (MMR) vaccine in children.

Full 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.

Enrollment: 500 estimated patients

Sex: All

Ages: 6 to 6 months old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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500 participants in 4 patient groups

C.C. : Both MMR doses given on current schedule (9 months and 12 months)

Active Comparator group

Description:

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)

Treatment:

Biological: Measles-Mumps-Rubella vaccine (MMR)

M.C. : 1st MMR on modified schedule (6 months) and 2nd MMR on current schedule (12 months)

Experimental group

Description:

Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: * 6 months (= modified schedule) * 12 months, concomitant with other vaccines (= current Swiss schedule)

Treatment:

Biological: Measles-Mumps-Rubella vaccine (MMR)

C. M. : 1st MMR on current schedule (9 months) and 2nd MMR on modified schedule (13 months)

Experimental group

Description:

Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: * 9 months (= current Swiss schedule) * 13 months, distant from other vaccines (= modified schedule)

Treatment:

Biological: Measles-Mumps-Rubella vaccine (MMR)

M.M. : Both MMR doses given on modified schedule (6 months and 13 months)

Experimental group

Description:

Measles-mumps-rubella (MMR) vaccine 0.5 ml injected intramuscularly, at: * 6 months (= modified schedule) * 13 months, distant from other vaccines (= modified schedule)

Treatment:

Biological: Measles-Mumps-Rubella vaccine (MMR)