Immunological and Genetic Risk factors for Cardiac Serious Adverse Events following Controlled Human Malaria Infections: a Case-Control study

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 25

Inclusion Criteria

In order to be eligible to participate in this study as a case, a subject must
meet all of the following criteria:
1. Subject must sign written informed consent to participate in the trial.
2. By judgement of the clinical investigator, the subject is able to understand
the planned study procedures and (limited) risks associated with the study,
inc. the risk of incidental findings in genetic analysis.
3. The subject was enrolled in a CHMI study performed by the Radboudumc between
January 1998 and December 2021 and was subjected to a Controlled Human Malaria
Infection. Subject developed a cardiac serious adverse event in the period of
20 days following CHMI. A cardiac SAE is defined as either clinically
significant increased troponin levels and/or diagnosis of myocarditis, acute
coronary syndrome or myocardial infarction by a cardiologist, and meet the
criteria of an SAE as defined in the study protocol.
4. Subjects unwilling and/or unable to participate in genetic analysis, are
still eligible for immunological analysis (and vice versa).

In order to be eligible to participate in this study as a control, a subject
must meet all of the following criteria:
1. The subject has signed written informed consent.
2. The subject is able to understand the study procedures and (limited) risks
associated with the study.
3. The subject was enrolled in a CHMI study performed by the Radboudumc between
January 1998 and December 2021 and was subjected to a Controlled Human Malaria
Infection. Subject did not develop a cardiac serious adverse event in the
period of 20 days following CHMI. A cardiac SAE is defined as either
clinically significant increased troponin levels and/or diagnosis of
myocarditis, acute coronary syndrome or myocardial infarction by a
cardiologist, and meets the criteria of an SAE as defined in the respective
study protocol.

Exclusion Criteria

A potential case or control subject who meets any of the following criteria
will be excluded from participation in immunological screening:
1. Subject is HIV-positive or suffers from any other (acute or chronic) disease
as determined by medical history, physical examination or laboratory screening
tests which according to the clinical judgment of the investigator leads to
undesirable interference with the results of the immunological tests. The
clinical investigator will consider whether blood samples without such
interference can be obtained later in the study period (e.g. in case of acute
infectious disease).
2. Use or receipt of
i) immunosuppressive drugs or other immune modifying drugs within three months
prior to blood sampling for immunological screening (inhaled and topical
corticosteroids and oral anti-histamines exempted) OR
ii) use of illicit drugs determined through urine drug screening OR
iii) any vaccinations within 30 days prior to immunology blood sampling
IF use of these drugs or receipt of a vaccination lead to undesirable
interference with the results of the immunological tests according to the
clinical judgment of the investigator. The clinical investigator will consider
whether blood samples without such interference can be obtained later in the
study period.
3. Any history of malaria other than CHMI as part of the Radboudumc trial in
which the subject has previously participated.

A potential case subject who meets any of the following criteria will be
excluded from participation in genetic analysis:
1. A history of bone marrow transplantation.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. Immunological risk factors with significant odds ratios for cardiac SAEs<br /><br>following CHMI, i.e. in cases compared to controls.<br /><br>2. Genetic factors/deviations/variants identified in one or more cases which<br /><br>can (possibly and/or partially) explain why these subjects suffered cardiac<br /><br>SAEs following CHMI.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Immunological factors/deviations/variants identified in one or more cases<br /><br>which can (possibly and/or partially) explain why these subjects suffered<br /><br>cardiac SAEs following CHMI.</p><br>