Ignite Creation Date:
2024-05-06 @ 4:10 PM
Last Modification Date:
2024-10-26 @ 2:05 PM
Study NCT ID:
NCT04899765
Status:
RECRUITING
Last Update Posted:
2024-01-19
First Post:
2021-05-18
Brief Title:
Measles and BCG Vaccines for Mother and Child
Sponsor:
Bandim Health Project
Organization:
Bandim Health Project
Study Overview
Official Title:
Specific and Non-specific Effects of Measles and BCG Vaccines for Mother and Child
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MATVAC
Brief Summary:
In Africa the mortality from infectious diseases remains high The investigators have discovered that live vaccines such as the BCG vaccine against tuberculosis and the measles vaccine can strengthen resistance to other infections they have beneficial non-specific effects The investigators have now seen signs that these non-specific effects for children are stronger if their mother has been given the same vaccines
In Africa BCG vaccine is recommended at birth and measles vaccine at 9 months of age They are not used beyond childhood
The investigators will randomize 2400 women to BCG vaccine measles vaccine or placebo The investigators will further randomize their children to an extra early measles vaccine or placebo The investigators will assess which of the resulting six vaccination schedules are best for womens and childrens protection against measles for the childs immune system and for general health
The project will be the first in the world to investigate the importance of vaccinating women with live vaccines
In Africa BCG vaccine is recommended at birth and measles vaccine at 9 months of age They are not used beyond childhood
The investigators will randomize 2400 women to BCG vaccine measles vaccine or placebo The investigators will further randomize their children to an extra early measles vaccine or placebo The investigators will assess which of the resulting six vaccination schedules are best for womens and childrens protection against measles for the childs immune system and for general health
The project will be the first in the world to investigate the importance of vaccinating women with live vaccines
Detailed Description:
OBJECTIVES The investigators aim to study the effects of providing measles vaccine MV or Bacille Calmette-Guérin vaccine BCG to women of fertile age prior to pregnancy and to study the added effect of providing MV earlier to their children for measles-specific and non-specific immunity in the child and for overall health in mother and child
Specific objectives
To study the interaction of maternal MV and BCG and early infant MV with respect to
the magnitude of the measles-specific antibody response in women and children
the proportion of children with maternal measles antibodies at the time of measles immunization
the viral load following YF vaccination in children
overall health in women and children
HYPOTHESES
Providing MV to women in the fertile age will increase the proportion of children who are vaccinated in the presence of maternal measles antibody both at 20 weeks and 9 months of age
Providing MV or BCG to women in the fertile age will reduce the childs viral load after a YF vaccine provided at 9 months of age
Providing MV or BCG to women in the fertile age will reduce maternal and child infectious disease morbidity by 20
METHODS The study will take place at the Bandim Health Project BHP Bissau Guinea-Bissau
The investigators plan a 3-by-2 factorial trial with randomization of non-pregnant women of fertile age to MV BCG or placebo and randomization of their offspring who will all get BCG at birth according to recommendations to early MV or no early MV at 20 weeks of age All children will get the recommended MV by 9 months of age
The study will enroll 2400 non-pregnant HIV-negative women who will be randomized 111 to one of three injections BCG MV or placebo saline The first 100 children born to mothers from each of the three groups and surviving until 20 weeks of age will be selected for follow-up Within strata of maternal vaccination BCG MV placebo they will be randomized 11 to early MV at 20 weeks or placebo saline Thus a total of 6 groups A-F will be formed
By 9 months of age 20 children in each randomization group will receive a yellow fever YF vaccine and then MV 5 days later All other children will receive an MV and a YF vaccine when they reach 9 months of age
Setting
BHPs Health and Demographic Surveillance System HDSS covers six districts in the capital of Guinea-Bissau with around 100000 individuals The BHP follows all women of fertile age with monthly visits to register new pregnancies All children are followed with 4-monthly home visits for infections hospitalizations and vaccinations All vaccinations administered at the three health centers in the study area are documented by BHP Furthermore BHP monitors all consultations and admissions at the health centers and all pediatric consultations and admissions at the national hospital
Enrolment and randomization of women
Eligible women will be identified through the BHP HDSS They will receive a home visit by a project assistant who will explain the study If they are interested in participating they will be asked to come to a nearby health center Here following informed oral and written consent a blood sample will be drawn and tested for HIV If the HIV-test is positive immediate counseling will be given by a trained project nurse and the woman will be referred to the HIV clinic per current standard of care A urine pregnancy test will be carried out Provided negative HIV and pregnancy tests an interview regarding background factors including previous vaccinations will be carried out Finally the woman will be randomized and treated according to the allocation
Follow-up for pregnancies and morbidity
Women will be followed for pregnancy All participating women will also be followed with respect to morbidity consultations hospitalizations at 2-monthly interviews and continuous documentation of hospitalizations and consultations
Maternal blood samples
All blood will be collected into Na-Heparin tubes Baseline blood sample All women enrolled will have a blood sample obtained by venipuncture at baseline in conjunction with the HIV screening just before randomization
Baseline4weeks blood sample A blood sample will be obtained after 4 weeks from 30 women from each group These samples with be paired with the baseline sample to assess measles-specific antibodies level
Children
All children will be followed closely through monthly home visits during which the mother will be encouraged to bring her child for the scheduled vaccines At 20 weeks of age the children will be invited for further randomization
Inclusion criteria The first 100 children surviving until 20 weeks of age from each group of enrolled mothers and having received all recommended vaccines the 3rd pentavalent vaccine at least 6 weeks before are eligible for further study randomization
Exclusion criteria Exclusion criteria are lack of receipt of all scheduled vaccines pentavalent vaccine less than 6 weeks ago in which case children are asked to come back once 6 weeks are reached and overt illness in which case they will be referred for treatment and invited to come back when the child is well again
Randomization of children
Eligible children are identified at the monthly home visits and asked to come to a nearby health center in the afternoon Here provided maternal consent they will be randomly allocated to early MV or placebo saline
Child blood samples
All blood will be collected into Na-Heparin tubes Measles specific arm N30 from each of Groups A-F A 2 ml blood sample will be obtained at baseline either 20 weeks of age or 9 months of age and a second sample of 2 ml will be obtained at either 9 months of age those bled first at 20 weeks of age or 18 weeks after 9-month-vaccination those bled first at 9 months of age for assessment of measles-specific antibodies levels
Non-specific effect arm N20 from each of Groups A-F Children will receive YF vaccine at 9 months of age a blood sample will be obtained just before and a second sample will be obtained 5 days later for assessment of YF viraemia
Follow up for child morbidity and mortality
The 300 children enrolled in the child-vaccination part of the study as well as other children born to the 2400 women enrolled in the maternal vaccination study will be followed for morbidity and mortality The data collection with be based on the HDSS regular home visits the registration of consultations in the study area and the registration of admissions to the pediatric ward of the national hospital
Vaccination and blinding
Women vaccination Women will be vaccinated in right upper arm The vaccine administrator will know what is given but the women will not be told before the trial has come to an end
Child vaccination MV and YF vaccine will be given subcutaneously according to the national recommendations Placebo for MV at 20 weeks will be saline provided subcutaneously in the same volume as MV
Analysis of blood samples
The blood samples will be analyzed in collaboration with our international colleagues
Measles antibodies Total and measles-specific immunoglobulin G IgG levels will be analyzed
YF vaccine response Children will receive a single dose of YF vaccine A blood sample will be obtained 5 days after and tested for yellow fever viral load
Statistical analysis and sample size
Maternal and child morbidity data will be analyzed in standard survival analysis for time-to-event data to compare potential differential effects by vaccination allocation The analysis will take into account other possible interventions or events campaigns or epidemics occurring during the period of follow-up
The study sample size of 2400 women is based on the anticipated delivery rates in the area Based on census data from BHP the annual incidence of new deliveries in women with one child of 12 months will be around 15 Hence with a cohort of 2400 enrolled women it is expected to register 300 deliveries in the 5th -10th trimester after enrolment starts
Specific objectives
To study the interaction of maternal MV and BCG and early infant MV with respect to
the magnitude of the measles-specific antibody response in women and children
the proportion of children with maternal measles antibodies at the time of measles immunization
the viral load following YF vaccination in children
overall health in women and children
HYPOTHESES
Providing MV to women in the fertile age will increase the proportion of children who are vaccinated in the presence of maternal measles antibody both at 20 weeks and 9 months of age
Providing MV or BCG to women in the fertile age will reduce the childs viral load after a YF vaccine provided at 9 months of age
Providing MV or BCG to women in the fertile age will reduce maternal and child infectious disease morbidity by 20
METHODS The study will take place at the Bandim Health Project BHP Bissau Guinea-Bissau
The investigators plan a 3-by-2 factorial trial with randomization of non-pregnant women of fertile age to MV BCG or placebo and randomization of their offspring who will all get BCG at birth according to recommendations to early MV or no early MV at 20 weeks of age All children will get the recommended MV by 9 months of age
The study will enroll 2400 non-pregnant HIV-negative women who will be randomized 111 to one of three injections BCG MV or placebo saline The first 100 children born to mothers from each of the three groups and surviving until 20 weeks of age will be selected for follow-up Within strata of maternal vaccination BCG MV placebo they will be randomized 11 to early MV at 20 weeks or placebo saline Thus a total of 6 groups A-F will be formed
By 9 months of age 20 children in each randomization group will receive a yellow fever YF vaccine and then MV 5 days later All other children will receive an MV and a YF vaccine when they reach 9 months of age
Setting
BHPs Health and Demographic Surveillance System HDSS covers six districts in the capital of Guinea-Bissau with around 100000 individuals The BHP follows all women of fertile age with monthly visits to register new pregnancies All children are followed with 4-monthly home visits for infections hospitalizations and vaccinations All vaccinations administered at the three health centers in the study area are documented by BHP Furthermore BHP monitors all consultations and admissions at the health centers and all pediatric consultations and admissions at the national hospital
Enrolment and randomization of women
Eligible women will be identified through the BHP HDSS They will receive a home visit by a project assistant who will explain the study If they are interested in participating they will be asked to come to a nearby health center Here following informed oral and written consent a blood sample will be drawn and tested for HIV If the HIV-test is positive immediate counseling will be given by a trained project nurse and the woman will be referred to the HIV clinic per current standard of care A urine pregnancy test will be carried out Provided negative HIV and pregnancy tests an interview regarding background factors including previous vaccinations will be carried out Finally the woman will be randomized and treated according to the allocation
Follow-up for pregnancies and morbidity
Women will be followed for pregnancy All participating women will also be followed with respect to morbidity consultations hospitalizations at 2-monthly interviews and continuous documentation of hospitalizations and consultations
Maternal blood samples
All blood will be collected into Na-Heparin tubes Baseline blood sample All women enrolled will have a blood sample obtained by venipuncture at baseline in conjunction with the HIV screening just before randomization
Baseline4weeks blood sample A blood sample will be obtained after 4 weeks from 30 women from each group These samples with be paired with the baseline sample to assess measles-specific antibodies level
Children
All children will be followed closely through monthly home visits during which the mother will be encouraged to bring her child for the scheduled vaccines At 20 weeks of age the children will be invited for further randomization
Inclusion criteria The first 100 children surviving until 20 weeks of age from each group of enrolled mothers and having received all recommended vaccines the 3rd pentavalent vaccine at least 6 weeks before are eligible for further study randomization
Exclusion criteria Exclusion criteria are lack of receipt of all scheduled vaccines pentavalent vaccine less than 6 weeks ago in which case children are asked to come back once 6 weeks are reached and overt illness in which case they will be referred for treatment and invited to come back when the child is well again
Randomization of children
Eligible children are identified at the monthly home visits and asked to come to a nearby health center in the afternoon Here provided maternal consent they will be randomly allocated to early MV or placebo saline
Child blood samples
All blood will be collected into Na-Heparin tubes Measles specific arm N30 from each of Groups A-F A 2 ml blood sample will be obtained at baseline either 20 weeks of age or 9 months of age and a second sample of 2 ml will be obtained at either 9 months of age those bled first at 20 weeks of age or 18 weeks after 9-month-vaccination those bled first at 9 months of age for assessment of measles-specific antibodies levels
Non-specific effect arm N20 from each of Groups A-F Children will receive YF vaccine at 9 months of age a blood sample will be obtained just before and a second sample will be obtained 5 days later for assessment of YF viraemia
Follow up for child morbidity and mortality
The 300 children enrolled in the child-vaccination part of the study as well as other children born to the 2400 women enrolled in the maternal vaccination study will be followed for morbidity and mortality The data collection with be based on the HDSS regular home visits the registration of consultations in the study area and the registration of admissions to the pediatric ward of the national hospital
Vaccination and blinding
Women vaccination Women will be vaccinated in right upper arm The vaccine administrator will know what is given but the women will not be told before the trial has come to an end
Child vaccination MV and YF vaccine will be given subcutaneously according to the national recommendations Placebo for MV at 20 weeks will be saline provided subcutaneously in the same volume as MV
Analysis of blood samples
The blood samples will be analyzed in collaboration with our international colleagues
Measles antibodies Total and measles-specific immunoglobulin G IgG levels will be analyzed
YF vaccine response Children will receive a single dose of YF vaccine A blood sample will be obtained 5 days after and tested for yellow fever viral load
Statistical analysis and sample size
Maternal and child morbidity data will be analyzed in standard survival analysis for time-to-event data to compare potential differential effects by vaccination allocation The analysis will take into account other possible interventions or events campaigns or epidemics occurring during the period of follow-up
The study sample size of 2400 women is based on the anticipated delivery rates in the area Based on census data from BHP the annual incidence of new deliveries in women with one child of 12 months will be around 15 Hence with a cohort of 2400 enrolled women it is expected to register 300 deliveries in the 5th -10th trimester after enrolment starts
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None