Plasmodium FalciparumNCT04445103
The Malaria Heart Disease Study
An observational study of Plasmodium Falciparum and Plasmodium Vivax, run by University Hospital, Gentofte, Copenhagen at 1 site in Brazil.
Trial summary
The Malaria Heart Disease Study is a prospective longitudinal cohort study of a random sample of approximately 1200 individuals from the state of Acre in Brazil. The overall hypothesis is that patients who have (i) previously suffered from a malaria infection or (ii) patients with ongoing symptomatic malaria will… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Plasmodium Falciparum, Plasmodium Vivax, Heart Diseases
- What is being tested?
- Assessment of cardiac function
- How many people
- 597 participants
- Where
- 1 siteBrazil
- Study dates
- 21 Jun 2020to 25 Jan 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study population conforms to three study groups: i) History of malaria infection ii) Controls and iii) Symptomatic malaria infection
Group 1 (History of malaria) Inclusion: Patients with a record of malaria >=18 years old will be invited at random Exclusion: Persons not able to cooperate and persons unwilling or unable to understand and sign "informed consent", persons who are hospitalized due to severe malaria
Group 2 (Controls) Inclusion: Patients with no record of malaria >=18 years old will be invited at random Exclusion: Persons not able to cooperate and persons unwilling or unable to understand and sign "informed consent"
Group 3 (Symptomatic malaria) Inclusion: Patients >=18 years old diagnosed in outpatient/inpatient clinic with malaria infection by thick and thin blood smear and/or rapid diagnostic test. Enrollment of both severe (complicated) and uncomplicated malaria cases as defined by the WHO criteria. Exclusion: Persons not able to cooperate and persons unwilling or unable to understand and sign "informed consent", suspected or verified concomitant protozoal infections
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Malaria Heart Disease Study: A Novel Pathway to Subclinical Heart Disease
The Malaria Heart Disease Study is a prospective longitudinal cohort study of a random sample of approximately 1200 individuals from the state of Acre in Brazil. The overall hypothesis is that patients who have (i) previously suffered from a malaria infection or (ii) patients with ongoing symptomatic malaria will benefit from having an echocardiogram and blood tests performed as a screening tool to diagnose early cardiac impairment and prevent future cardiovascular disease.
Read the detailed description
The purpose of this study is to investigate the relationship between exposure to malaria and the risk of developing subclinical and manifest cardiovascular disease. The study is conducted in the high endemic malaria zone pertaining to the city of Cruzeiro do Sul, located in the state of Acre, Brazil. The city is considered a part of the Amazon basin.
By invitation of a random sample of patients with a history of malaria, controls with no history of malaria, and symptomatic patients with ongoing malaria infection, the aim is to elucidate potential pathways linking malaria to cardiovascular disease.
Aim 1: Determine whether prior exposure to malaria is associated with myocardial dysfunction. The investigators hypothesize that adults with a history of treated malaria (cases) will have worse left ventricular (LV) diastolic function and systolic strain compared to age- and sex-matched controls without a history of malaria infection. The investigators will recruit 500 cases and 500 controls from Cruzeiro-do-Sul, Brazil. State-of-the-art ultrasonographic examinations will be used to asses novel imaging metrics of cardiac function.
Aim 2: Define the extent to which proinflammatory factors (such as Ang-2, CRP, VEGF) are associated with cardiac dysfunction in subjects with a history of malaria. The investigators hypothesize that proinflammatory biomarkers will be higher in cases compared to controls, and that higher concentrations of inflammatory markers will associate with worse LV diastolic function and strain. The investigators will measure inflammatory biomarkers, determine the association with cardiac dysfunction, and test whether history of malaria modifies this association.
Aim 3: Determine if echocardiographic parameters of systolic and diastolic function and cardiac biomarkers are significantly elevated in patients with symptomatic malaria (N=200).
Upon conclusion of this study, the investigators will better understand the relationship of malaria with subclinical cardiac dysfunction. This will allow development of the scientific foundation and necessary infrastructure to expand this project to a longitudinal study to prospectively assess associations with relevant clinical outcomes.
- Being tested
- Assessment of cardiac function
- Keywords
- Echocardiography, Endothelial dysfunction, Cardiovascular inflammation
- Medical subject headings
- Malaria, Falciparum, Malaria, Vivax, Heart Diseases, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Assessment of cardiac functionDiagnostic test
Echocardiographic examination and assessment of cardiac biomakers
| Study group | Role | What they receive |
|---|---|---|
| History of malaria | Individuals with a history of malaria infection Receives: Diagnostic Test: Assessment of cardiac function | |
| Controls | Individuals without a history of malaria infection Receives: Diagnostic Test: Assessment of cardiac function | |
| Symptomatic malaria | Patients with symptomatic malaria infection (complicated and uncomplicated) Receives: Diagnostic Test: Assessment of cardiac function |
What is being measured
The primary outcome is the main question the study is designed to answer.
Echocardiography
Alterations in systolic and diastolic function assessed by conventional and speckle tracking echocardiography
Measured: 2020-2023
Biomarkers
Elevated cardiac biomarkers
Measured: 2020-2023
Secondary outcomes (2)
Endothelial dysfunction
Elevated markers of endothelial dysfunction
Measured: 2020-2023
Inflammation
Elevated proinflammatory markers
Measured: 2020-2023
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2020
- Study start21 Jun 2020
- Primary completion25 Jan 2021
- Study completion25 Jan 2021
Why it stopped: Due to the COVID-19 pandemic it was not possible to complete the study inclusion as originally anticipated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Plasmodium FalciparumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 597 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Federal University of Acre, University of Sao Paulo, Independent Research Fund Denmark
- Responsible party
- Principal investigator, Philip Brainin, University Hospital, Gentofte, Copenhagen
- Investigators
- Philip Brainin, MD, PhD, Principal investigator, Federal University of AcreOdilson Silvestre, MD, PhD, MPH, Principal investigator, Federal University of AcreTor Biering-Sørensen, MD, PhD, MPH, Principal investigator, Gentofte University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04445103
- Sponsor's protocol ID
- 68999970512
- Status last verified
- Jul 2022
- First submitted
- 21 Jun 2020
- Last updated
- 19 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Wegener A, Lima KO, Holm AE, Gomes LC, Matos LO, Vieira IVM, Souza RM, Marinho CRF, Vestergaard LS, Biering-Sorensen T, Silvestre OM, Brainin P. Cardiopulmonary alterations by ultrasound in a patient with uncomplicated mixed malaria infection: a case report from the Amazon Basin. Malar J. 2021 Jul 28;20(1):330. doi: 10.1186/s12936-021-03861-5.
PubMed 34321001Holm AE, Gomes LC, Lima KO, Wegener A, Matos LO, Vieira IVM, Kaagaard MD, Pareek M, de Souza RM, Marinho CRF, Biering-Sorensen T, Silvestre OM, Brainin P. Tropical diseases and risk of hypertension in the Amazon Basin: a cross-sectional study. J Hum Hypertens. 2022 Dec;36(12):1121-1127. doi: 10.1038/s41371-021-00633-1. Epub 2021 Nov 13.
PubMed 34775497Wegener A, Kaagaard MD, Gomes LC, Holm AE, Matos LO, Lima KO, Vieira IVM, de Souza RM, Olsen FJ, Marinho CRF, Biering-Sorensen T, Silvestre OM, Brainin P. Reference values for left ventricular dimensions, systolic and diastolic function: a study from the Amazon Basin of Brazil. Int J Cardiovasc Imaging. 2022 Apr;38(4):813-822. doi: 10.1007/s10554-021-02475-x. Epub 2021 Nov 22.
PubMed 34807316Kaagaard MD, Matos LO, Holm AE, Gomes LC, Wegener A, Lima KO, Vieira IVM, de Souza RM, Marinho CRF, Hviid L, Vestergaard LS, Dominguez H, Biering-Sorensen T, Silvestre OM, Brainin P. Frequency of Electrocardiographic Alterations and Pericardial Effusion in Patients With Uncomplicated Malaria. Am J Cardiol. 2022 Feb 15;165:116-123. doi: 10.1016/j.amjcard.2021.11.009. Epub 2021 Dec 12.
PubMed 34906368Wegener A, Holm AE, Gomes LC, Lima KO, Kaagaard MD, Matos LO, Vieira IVM, de Souza RM, Marinho CRF, Nascimento BR, Biering-Sorensen T, Silvestre OM, Brainin P. Prevalence of rheumatic heart disease in adults from the Brazilian Amazon Basin. Int J Cardiol. 2022 Apr 1;352:115-122. doi: 10.1016/j.ijcard.2022.01.026. Epub 2022 Jan 20.
PubMed 35065154Wegener A, Holm AE, Gomes LC, Lima KO, Matos LO, Vieira IVM, Kaagaard MD, de Souza RM, Hviid L, Guimaraes Lacerda MV, Vestergaard LS, Farias Marinho CR, Platz E, Biering-Sorensen T, Silvestre OM, Brainin P. Prevalence and Dynamic Changes in Lung Ultrasound Findings among Adults with Uncomplicated Malaria and Controls in the Amazon Basin, Brazil. Am J Trop Med Hyg. 2022 Apr 11;106(6):1637-1645. doi: 10.4269/ajtmh.21-1107. Print 2022 Jun 15.
PubMed 35405640Holm AE, Gomes LC, Wegener A, Lima KO, Matos LO, Vieira IVM, Kaagaard MD, Pareek M, de Souza RM, Marinho CRF, Biering-Sorensen T, Silvestre OM, Brainin P. Is self-rated health associated with cardiovascular risk factors and disease in a low-income setting? A cross-sectional study from the Amazon Basin of Brazil. BMJ Open. 2022 Aug 30;12(8):e058277. doi: 10.1136/bmjopen-2021-058277.
PubMed 36041756
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Malaria Heart Disease Study: A Novel Pathway to Subclinical Heart Disease
- ClinicalTrials.gov ID
- NCT04445103
- Acronym / sponsor ID
- 68999970512
- Keywords
- Echocardiography, Endothelial dysfunction, Cardiovascular inflammation
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Due to the COVID-19 pandemic it was not possible to complete the study inclusion as originally anticipated.
- Enrolment
- 597 participants (actual)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Collaborators
- Federal University of Acre, University of Sao Paulo, Independent Research Fund Denmark
- Study start
- 21 Jun 2020 (actual)
- Primary completion
- 25 Jan 2021 (actual)
- Study completion
- 25 Jan 2021 (actual)
- First posted
- 24 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Malaria Heart Disease Study is a prospective longitudinal cohort study of a random sample of approximately 1200 individuals from the state of Acre in Brazil. The overall hypothesis is that patients who have (i) previously suffered from a malaria infection or (ii) patients with ongoing symptomatic malaria will benefit from having an echocardiogram and blood tests performed as a screening tool to diagnose early cardiac impairment and prevent future cardiovascular disease.
Detailed description
The purpose of this study is to investigate the relationship between exposure to malaria and the risk of developing subclinical and manifest cardiovascular disease. The study is conducted in the high endemic malaria zone pertaining to the city of Cruzeiro do Sul, located in the state of Acre, Brazil. The city is considered a part of the Amazon basin.
By invitation of a random sample of patients with a history of malaria, controls with no history of malaria, and symptomatic patients with ongoing malaria infection, the aim is to elucidate potential pathways linking malaria to cardiovascular disease.
Aim 1: Determine whether prior exposure to malaria is associated with myocardial dysfunction. The investigators hypothesize that adults with a history of treated malaria (cases) will have worse left ventricular (LV) diastolic function and systolic strain compared to age- and sex-matched controls without a history of malaria infection. The investigators will recruit 500 cases and 500 controls from Cruzeiro-do-Sul, Brazil. State-of-the-art ultrasonographic examinations will be used to asses novel imaging metrics of cardiac function.
Aim 2: Define the extent to which proinflammatory factors (such as Ang-2, CRP, VEGF) are associated with cardiac dysfunction in subjects with a history of malaria. The investigators hypothesize that proinflammatory biomarkers will be higher in cases compared to controls, and that higher concentrations of inflammatory markers will associate with worse LV diastolic function and strain. The investigators will measure inflammatory biomarkers, determine the association with cardiac dysfunction, and test whether history of malaria modifies this association.
Aim 3: Determine if echocardiographic parameters of systolic and diastolic function and cardiac biomarkers are significantly elevated in patients with symptomatic malaria (N=200).
Upon conclusion of this study, the investigators will better understand the relationship of malaria with subclinical cardiac dysfunction. This will allow development of the scientific foundation and necessary infrastructure to expand this project to a longitudinal study to prospectively assess associations with relevant clinical outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| History of malaria | – | Diagnostic Test: Assessment of cardiac functionIndividuals with a history of malaria infection |
| Controls | – | Diagnostic Test: Assessment of cardiac functionIndividuals without a history of malaria infection |
| Symptomatic malaria | – | Diagnostic Test: Assessment of cardiac functionPatients with symptomatic malaria infection (complicated and uncomplicated) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study population conforms to three study groups: i) History of malaria infection ii) Controls and iii) Symptomatic malaria infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Assessment of cardiac functionEchocardiographic examination and assessment of cardiac biomakers | Diagnostic test | Controls, History of malaria, Symptomatic malaria |
Primary outcome
Echocardiography
Time frame: 2020-2023
Alterations in systolic and diastolic function assessed by conventional and speckle tracking echocardiography
Biomarkers
Time frame: 2020-2023
Elevated cardiac biomarkers
2 secondary outcomes
Endothelial dysfunction
Time frame: 2020-2023
Inflammation
Time frame: 2020-2023
Results and safety
The study was stopped early (reason given: Due to the COVID-19 pandemic it was not possible to complete the study inclusion as originally anticipated.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2022.
- Results publication: PubMed 34321001Wegener A, Lima KO, Holm AE, Gomes LC, Matos LO, Vieira IVM, Souza RM, Marinho CRF, Vestergaard LS, Biering-Sorensen T, Silvestre OM, Brainin P. Cardiopulmonary alterations by ultrasound in a patient with uncomplicated mixed malaria infection: a case report from the Amazon Basin. Malar J. 2021 Jul 28;20(1):330. doi: 10.1186/s12936-021-03861-5.
- Results publication: PubMed 34775497Holm AE, Gomes LC, Lima KO, Wegener A, Matos LO, Vieira IVM, Kaagaard MD, Pareek M, de Souza RM, Marinho CRF, Biering-Sorensen T, Silvestre OM, Brainin P. Tropical diseases and risk of hypertension in the Amazon Basin: a cross-sectional study. J Hum Hypertens. 2022 Dec;36(12):1121-1127. doi: 10.1038/s41371-021-00633-1. Epub 2021 Nov 13.
- Results publication: PubMed 34807316Wegener A, Kaagaard MD, Gomes LC, Holm AE, Matos LO, Lima KO, Vieira IVM, de Souza RM, Olsen FJ, Marinho CRF, Biering-Sorensen T, Silvestre OM, Brainin P. Reference values for left ventricular dimensions, systolic and diastolic function: a study from the Amazon Basin of Brazil. Int J Cardiovasc Imaging. 2022 Apr;38(4):813-822. doi: 10.1007/s10554-021-02475-x. Epub 2021 Nov 22.
- Results publication: PubMed 34906368Kaagaard MD, Matos LO, Holm AE, Gomes LC, Wegener A, Lima KO, Vieira IVM, de Souza RM, Marinho CRF, Hviid L, Vestergaard LS, Dominguez H, Biering-Sorensen T, Silvestre OM, Brainin P. Frequency of Electrocardiographic Alterations and Pericardial Effusion in Patients With Uncomplicated Malaria. Am J Cardiol. 2022 Feb 15;165:116-123. doi: 10.1016/j.amjcard.2021.11.009. Epub 2021 Dec 12.
- Results publication: PubMed 35065154Wegener A, Holm AE, Gomes LC, Lima KO, Kaagaard MD, Matos LO, Vieira IVM, de Souza RM, Marinho CRF, Nascimento BR, Biering-Sorensen T, Silvestre OM, Brainin P. Prevalence of rheumatic heart disease in adults from the Brazilian Amazon Basin. Int J Cardiol. 2022 Apr 1;352:115-122. doi: 10.1016/j.ijcard.2022.01.026. Epub 2022 Jan 20.
- Results publication: PubMed 35405640Wegener A, Holm AE, Gomes LC, Lima KO, Matos LO, Vieira IVM, Kaagaard MD, de Souza RM, Hviid L, Guimaraes Lacerda MV, Vestergaard LS, Farias Marinho CR, Platz E, Biering-Sorensen T, Silvestre OM, Brainin P. Prevalence and Dynamic Changes in Lung Ultrasound Findings among Adults with Uncomplicated Malaria and Controls in the Amazon Basin, Brazil. Am J Trop Med Hyg. 2022 Apr 11;106(6):1637-1645. doi: 10.4269/ajtmh.21-1107. Print 2022 Jun 15.
- Derived from this study: PubMed 36041756Holm AE, Gomes LC, Wegener A, Lima KO, Matos LO, Vieira IVM, Kaagaard MD, Pareek M, de Souza RM, Marinho CRF, Biering-Sorensen T, Silvestre OM, Brainin P. Is self-rated health associated with cardiovascular risk factors and disease in a low-income setting? A cross-sectional study from the Amazon Basin of Brazil. BMJ Open. 2022 Aug 30;12(8):e058277. doi: 10.1136/bmjopen-2021-058277.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip Brainin, MD, PhD principal investigator
Federal University of Acre
Odilson Silvestre, MD, PhD, MPH principal investigator
Federal University of Acre
Tor Biering-Sørensen, MD, PhD, MPH principal investigator
Gentofte University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Plasmodium Falciparum and Plasmodium Vivax, run by University Hospital, Gentofte, Copenhagen at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Due to the COVID-19 pandemic it was not possible to complete the study inclusion as originally anticipated.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Echocardiography (time frame: 2020-2023). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04445103, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2022.