Non-specific Effects of Vaccination on Mortality and Morbidity (NOVAC)

August 31, 2018 updated by: Radboud University Medical Center

The Non-specific Effects of Vaccination Related to Mortality and Morbidity in Nanoro Health and Demographic Surveillance System Cohort

It has long been recognized that the positive effects of vaccination on childhood mortality cannot be solely attributed to a decline in the disease targeted by the vaccine. These so-called non-specific effects of vaccination have so far mostly been linked to mortality. However, it has been suggested that non-specific effects may also effect morbidity and nutritional status. This study aims to further explore the correlation between vaccination, susceptibility to infectious diseases (particularly malaria and bacterial infections), nutritional status and immunity.

With this prospective cross sectional study among healthy individuals in rural west-Africa we aim to address several research questions at the same time. This study will assess the influence of (time-point of) vaccination on morbidity, mortality and immune status among healthy individuals in a rural sub-Saharan African setting. Secondly, to explore the prevalence of subclinical malaria, iron deficiency anemia, sickle cell anemia and thallasemia among a healthy rural sub-Saharan African population. And finally to assess normal hemocytometry values among a healthy rural sub-Saharan African population.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

A cross sectional study among healthy participants randomly selected from the population living in the Nanoro HDSS cohort to (a) study the relation between vaccination and morbidity (including hemoglobin levels, subclinical malaria and stunting) (b) perform hemocytometry in order to determine reference values for that population and estimate the prevalence and causes of anemia, using reference values from other Sub-Sahara Africa countries and industrialized countries.

In a cross sectional study among a healthy population in the Nanoro HDSS cohort, hemocytometry will be performed in order to define normal values for that population. In addition, hemoglobin levels can be related to the presence of iron deficiency, thalassemia and malaria and be corrected for important confounding factors, such as the family income, family composition, distance to a healthcare center and vaccination status. This study will allow to assess simultaneously the normal range of hemoglobin values, the prevalence of (different causes of) anemia, the prevalence of subclinical malaria parasitemia, as well as the influence of (timepoint of) vaccination on all these issues. It is hypothized that early vaccination with live attenuated vaccines has a protective effect against malaria and other severe infectious diseases and will result in a better nutritional status, a higher hemoglobin level and a higher threshold of subclinical parasitemia. The protective effect of early vaccination with live attenuated vaccines may be due to the long-term modulation of the immune system through epigenetic changes causing a right balance between the pro- and anti-inflammatory responses. Such balance can be determined by ex-vivo stimulation of whole blood by a variety of stimuli, including Mycobacterium tuberculosis and lipopolysaccharide from Escherichia coli, followed by measurement of ex vivo cytokine production. Previous studies among healthy volunteers in the Netherlands have shown that BCG is indeed capable to induce epigenetic changes and influence immune response by influencing various pathways including through genetic variations in mTOR, HK2, PFKP, GLS, and GLUD1/2 (ref).

The new Sysmex analysers are not only capable to determine hemocytometry, but are at the same time capable to detect malaria parasites directly. Interestingly, not only the asexual stages of the parasites are detected but the gametocytes as well. This may be very important as gametocyte carriers are known to play a crucial role in malaria transmission. Gametocytes are presently detected by light microscopy or by PCR, however these techniques are limited; the sensitivity of light microscopy is relatively low and PCR is too complex to perform in most rural sub-Saharan African settings. The new Sysmex hematology analysers are easy to operate at low costs and may as such become an important tool for malaria elimination programs. No data are presently available about gametocyte density in Burkina Faso in a large population, nor is the lower level of detection of gametocytes using the sysmex analyzers known.

This research has four main objectives :

  1. To perform hemocytometry among a healthy rural Burkina Faso population selected from the Nanoro HDSS cohort, in order to determine reference values for that population.
  2. To perform hemocytometry among a healthy rural Burkina Faso population selected from the Nanoro HDSS cohort, in order to estimate the prevalence and causes of anemia, using reference values from other Sub-Sahara Africa (SSA) countries and industrialized countries.
  3. To study the relation between (timepoint of) vaccination and morbidity (including hemoglobin levels, subclinical malaria, bacterial infection and stunting) among a healthy rural Burkina Faso population selected from the Nanoro HDSS cohort. For this objective the population will be stratified by birth cohort.

  4. To perform ex-vivo whole blood stimulation to assess differences in immune response between patientgroups with a different vaccination status, within a healthy rural Burkina Faso population selected from the Nanoro HDSS cohort

    Seondary objectives

  5. To assess the detection limit of gametocyte carriages for the new series Sysmex hematology analyzers.
  6. To assess if Salmonella resides in blood as a reservoir for invasive infection among a rural Burkina Faso population selected from the Nanoro HDSS cohort.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1005

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Burkina Faso
    • Boulkiemedé
      • Nanoro, Boulkiemedé, Burkina Faso
        • Clinical Research Unit of Nanoro

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

A total of 5 groups will be selected. Each age group will consist of 220 participant (including 20% for potential non response). The survey will be conducted among 24 villages. Demographic age distribution is comparable for each of the villages. In order to prevent bias, a proportionate number of participants will be selected from each village based on its total population. Participants will then be randomly selected from each sample stratum using systematic selection.

Description

Inclusion Criteria:

  • Healthy participants currently living in the Nanoro HDSS area, born before May 2016.

Exclusion Criteria:

  • Current febrile illness,
  • Current chronic illnesses, HIV, TB, renal failure, cardiac disease (if known)
  • Patients that have participated in the RTSS vaccination trial from Glaxo-Smith-Kline at the same inclusion site.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Children of 1 years old
200 healthy volunteers aged between 12 and 23 months
Other: Venipuncture
  1. Full blood count and leukocyte differentiation.
  2. Detection of malaria parasites and parasite differentiation to trophozoites, gametocytes and ringstages (XN-30)
  3. Detection of anemia, thallasemia and sickle cell anemia (XN-20)
  4. Ex-vivo stimulation of wholeblood with various stimuli. Read-out will be a spectrum of cytokines (ELISA)
  5. Circulating cytokines and inflammatory markers (ELIZA)
  6. DNA analysis to assess genetic variations determining pro- versus anti inflammatory response including mTOR, HK2, PFKP, GLS, and GLUD1/2.
  7. pan-Salmonella PCR
  8. Gametocyte PCR
Children aged 2-4
200 healthy volunteers aged between 24 and 59 months
Other: Venipuncture
  1. Full blood count and leukocyte differentiation.
  2. Detection of malaria parasites and parasite differentiation to trophozoites, gametocytes and ringstages (XN-30)
  3. Detection of anemia, thallasemia and sickle cell anemia (XN-20)
  4. Ex-vivo stimulation of wholeblood with various stimuli. Read-out will be a spectrum of cytokines (ELISA)
  5. Circulating cytokines and inflammatory markers (ELIZA)
  6. DNA analysis to assess genetic variations determining pro- versus anti inflammatory response including mTOR, HK2, PFKP, GLS, and GLUD1/2.
  7. pan-Salmonella PCR
  8. Gametocyte PCR
Children aged 5 - 9
200 healthy volunteers aged between 60 and 119 months
Other: Venipuncture
  1. Full blood count and leukocyte differentiation.
  2. Detection of malaria parasites and parasite differentiation to trophozoites, gametocytes and ringstages (XN-30)
  3. Detection of anemia, thallasemia and sickle cell anemia (XN-20)
  4. Ex-vivo stimulation of wholeblood with various stimuli. Read-out will be a spectrum of cytokines (ELISA)
  5. Circulating cytokines and inflammatory markers (ELIZA)
  6. DNA analysis to assess genetic variations determining pro- versus anti inflammatory response including mTOR, HK2, PFKP, GLS, and GLUD1/2.
  7. pan-Salmonella PCR
  8. Gametocyte PCR
Children aged 10 - 14
200 healthy volunteers aged between 120 and 179 months
Other: Venipuncture
  1. Full blood count and leukocyte differentiation.
  2. Detection of malaria parasites and parasite differentiation to trophozoites, gametocytes and ringstages (XN-30)
  3. Detection of anemia, thallasemia and sickle cell anemia (XN-20)
  4. Ex-vivo stimulation of wholeblood with various stimuli. Read-out will be a spectrum of cytokines (ELISA)
  5. Circulating cytokines and inflammatory markers (ELIZA)
  6. DNA analysis to assess genetic variations determining pro- versus anti inflammatory response including mTOR, HK2, PFKP, GLS, and GLUD1/2.
  7. pan-Salmonella PCR
  8. Gametocyte PCR
Adults of 15 years and older
200 healthy volunteers of 180 months or older
Other: Venipuncture
  1. Full blood count and leukocyte differentiation.
  2. Detection of malaria parasites and parasite differentiation to trophozoites, gametocytes and ringstages (XN-30)
  3. Detection of anemia, thallasemia and sickle cell anemia (XN-20)
  4. Ex-vivo stimulation of wholeblood with various stimuli. Read-out will be a spectrum of cytokines (ELISA)
  5. Circulating cytokines and inflammatory markers (ELIZA)
  6. DNA analysis to assess genetic variations determining pro- versus anti inflammatory response including mTOR, HK2, PFKP, GLS, and GLUD1/2.
  7. pan-Salmonella PCR
  8. Gametocyte PCR

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Vaccination data
Time Frame: June 2017 - December 2017
Vaccination data as recorded on the vaccination card
June 2017 - December 2017
Nutritional status (Z-score or BMI)
Time Frame: June 2017 - December 2017
weight (kg), height (cm) and upperarm circumference (mm) leading to outcome measure on nutritional status: as appropriate Z-score or BMI
June 2017 - December 2017
History of disease
Time Frame: June 2017 - December 2017
Recorded history of disease according to the participants health card
June 2017 - December 2017
Immunological profile
Time Frame: June 2017 - December 2017
Cytokine levels, including IL-1b, IL-6, IL-10, IFN-gamma, TNF-alpha and IL-17, which will be assessed through ELISA. Measurement will be done on stimulated and unstimulated blood. Ex-vivo whole blood stimulation will be done with RPMI, LPS, MTB, Staphylococcus aureus, Candida albicans and Salmonella Typhimurium.
June 2017 - December 2017
Genetic immunological profile
Time Frame: June 2017 - December 2017
DNA analysis to assess genetic variations determining pro- versus anti inflammatory response including mTOR, HK2, PFKP, GLS, and GLUD1/2.
June 2017 - December 2017
subclinical parasitemia
Time Frame: June 2017 - December 2017
low level malaria infection detected by SYSMEX hematology analyzer XN - 30
June 2017 - December 2017
Anemia
Time Frame: June 2017 - December 2017
Differentiation of different forms of anemia using SYSMEX hematology analyzers XN -20 and XN - 30
June 2017 - December 2017
Reference values for hemocytometry in a healthy rural population from Burkina Faso
Time Frame: June 2017 - December 2017
Hemocytometry using SYSMEX hematology analyzers XN -20 and XN - 30
June 2017 - December 2017

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Gametocyte PCR
Time Frame: June 2017 - December 2017
Gametocyte PCR on EDTA whole blood stored in RNA protect
June 2017 - December 2017

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Salmonella PCR
Time Frame: June 2017 - December 2017
Salmonella PCR on EDTA whole blood (ethical clearance not yet obtained, amendment in progress)
June 2017 - December 2017

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Radboud University Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Clinical Research Unit of Nanoro

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: André van der Ven, Prof. Dr., Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 17, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2017

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 18, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 2, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 5, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 4, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 31, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2017-3339

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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