MalariaNCT02504918
Markers of T Cell Suppression: Associations With Malaria Infection and Antimalarial Treatment in Malian Children
An observational study of Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
Trial summary
Background: The disease malaria can cause very serious health problems. Researchers want to see if malaria affects the way T cells and vaccines work in the body. If it does, they may need to give malaria treatments before vaccines. They want to check the T cells in children who do or do not get antimalarial treatment. Read more about this study
- Who is it for?
- Ages 12 to 59 monthsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- How many people
- 200 participants
- Where
- 1 siteMali
- Study dates
- 21 Jul 2015to 12 Jun 2018
- 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 12 to 59 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- A study participant must satisfy the following criteria to be enrolled in this study:
- A child between 12-59 months
- Parent/guardian able to provide consent
- Resident of the health district of Ouelessebougou or neighboring district for at least a year
Who cannot join
- Clinically symptomatic or apparent severe anemia or any other condition that may be worsened by 5 mL phlebotomy or any other study procedure
- Chronic or debilitating condition that precludes attendance for monthly visits
- Known or clinically apparent condition of immunosuppression or chronic infection.
- Known allergies to study treatments (SP; amodiaquine; artemether-lumefantrine)
- Use of cotrimaxozale on a routine basis for prophylaxis
- Conditions that in the judgment of the investigator could increase the risk to the volunteer.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Markers of T Cell Suppression: Associations With Malaria Infection and Antimalarial Treatment
Background:
- The disease malaria can cause very serious health problems. Researchers want to see if malaria affects the way T cells and vaccines work in the body. If it does, they may need to give malaria treatments before vaccines. They want to check the T cells in children who do or do not get antimalarial treatment.
Read more
Objectives:
- To study the effect of blood stage malaria on T cell suppression and vaccine responses. To describe markers of T cell suppression in children who do or do not receive antimalarial treatment.
Eligibility:
- Children ages 12 59 months living near Ouelessebougou in Mali. They must have no serious illness.
Design:
- Participants will be screened with medical history and physical exam.
- Some participants will get a course of antimalarial tablets. Some will not. This will be decided at random.
- Participants will have monthly visits for up to a year. They will have blood tests at each visit.
Read the detailed description
Malaria caused by Plasmodium falciparum continues to be a global problem with devastating consequences. New interventions are needed to combat malaria, and progress is being made in development of vaccines: a subunit vaccine called RTSS confers partial protection against clinical malaria in children and is nearing licensure; a whole organism product called PfSPZ Vaccine can confer sterile protection against infection, and is now undergoing field trials. NIAID is involved in field trials of PfSPZ Vaccine and other vaccines, and a key question in vaccine trial design has been whether concurrent parasitemia will impair vaccine responses. The primary hypothesis in this study is that T cell suppression and regulation will decrease following antimalarial treatment that clears blood stage parasites for an extended period of time.
Up to 200 children will be recruited into longitudinal studies that will be conducted in Ouelessebougou and neighboring villages in Mali. In August 2015, up to 50 children presenting for Seasonal Malaria Chemoprevention (SMC) in a village where the government has implemented SMC will be enrolled, as well as up to 50 age-matched children residing in an adjacent village where SMC has not been implemented by the government of Mali; and then followed through the rainy season. In January 2016, up to 100 healthy children in Ouelessebougou village area will be enrolled and randomized to receive or not receive a course of artemether-lumefantrine, and then followed for the duration of the dry season (Jan-Jun 2016) and the subsequent rainy season (Jul-Dec 2016). Samples in both cohort studies (age-matched SMC study; randomized artemether-lumefantrine study) will be collected from the children at the time of monthly visits and assessed in ex vivo assays for markers of T cell suppression as the primary outcome of this study. For our secondary outcomes, we will examine levels of regulatory T cells, measure T cell responses in stimulation assays, and survey parasitemia by blood smear and by polymerase chain reaction (PCR) assays. We expect that levels of T cell suppression and regulatory T cells will be similar between groups before antimalarial treatment or malaria infection, but after treatment or in those subjects that remain uninfected these levels will be significantly lower as compared to the untreated and or infected subjects.
- Conditions
- Malaria
- Keywords
- Plasmodium Falciparum, Regulatory, Chemoprevention, Coartem, Parasitemia
- Medical subject headings
- Malaria, Malaria, Falciparum, Parasitemia
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate the association of recent malaria infection and percentage of PD1+ CD4 T cells in children that have not received SMC during the rainy season.
Measured: Approximately 3-6 months
To compare the percentage of PD1 +CD4 T cells in children who do or do not receive antimalarial treatment, in both rainy season and drythedry season.
Measured: Approximately 3-6 months
Secondary outcomes (3)
To compare and describe levels of regulatory T cells in children who do or do not receive antimalarial treatment, in both rainy season and dry season. To compare and describe T cell stimulation responses in children who do or do not receive anti...
Measured: Approximately 3-6 months
To determine and investigate phenotypic differences in T cell subsets in infected and uninfected subjects at baseline.
Measured: Approximately 3-6 months
To confirm that blood stage parasite burden is markedly reduced throughout the dry season by a single treatment with artemether-lumefantrine at enrollment; and to examine the association of parasite clearance during the dry season on malaria ris...
Measured: Approximately 3-6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study start21 Jul 2015
- Primary completion31 Dec 2016
- Study completion12 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- 200 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Michal Fried, Ph.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02504918
- Sponsor's protocol ID
- 999915163
- Other IDs
- 15-I-N163
- Status last verified
- 12 Jun 2018
- First submitted
- 21 Jul 2015
- Last updated
- 14 Jun 2018
- Results posted
- No
Publications
Cunnington AJ, Riley EM. Suppression of vaccine responses by malaria: insignificant or overlooked? Expert Rev Vaccines. 2010 Apr;9(4):409-29. doi: 10.1586/erv.10.16.
PubMed 20370551Dicko A, Diallo AI, Tembine I, Dicko Y, Dara N, Sidibe Y, Santara G, Diawara H, Conare T, Djimde A, Chandramohan D, Cousens S, Milligan PJ, Diallo DA, Doumbo OK, Greenwood B. Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Mali: a randomised, double-blind, placebo-controlled trial. PLoS Med. 2011 Feb 1;8(2):e1000407. doi: 10.1371/journal.pmed.1000407.
PubMed 21304923Wilson AL; IPTc Taskforce. A systematic review and meta-analysis of the efficacy and safety of intermittent preventive treatment of malaria in children (IPTc). PLoS One. 2011 Feb 14;6(2):e16976. doi: 10.1371/journal.pone.0016976.
PubMed 21340029Attaher O, Zaidi I, Kwan JL, Issiaka D, Samassekou MB, Cisse KB, Coulibaly B, Keita S, Sissoko S, Traore T, Diarra K, Diarra BS, Dembele A, Kanoute MB, Mahamar A, Barry A, Fried M, Dicko A, Duffy PE. Effect of Seasonal Malaria Chemoprevention on Immune Markers of Exhaustion and Regulation. J Infect Dis. 2020 Jan 1;221(1):138-145. doi: 10.1093/infdis/jiz415.
PubMed 31584094
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Markers of T Cell Suppression: Associations With Malaria Infection and Antimalarial Treatment
- ClinicalTrials.gov ID
- NCT02504918
- Acronym / sponsor ID
- 999915163
- Conditions
- Malaria
- Keywords
- Plasmodium Falciparum, Regulatory, Chemoprevention, Coartem, Parasitemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 21 Jul 2015
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 12 Jun 2018 (actual)
- First posted
- 22 Jul 2015 (estimated)
- 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.
Background:
- The disease malaria can cause very serious health problems. Researchers want to see if malaria affects the way T cells and vaccines work in the body. If it does, they may need to give malaria treatments before vaccines. They want to check the T cells in children who do or do not get antimalarial treatment.
Objectives:
- To study the effect of blood stage malaria on T cell suppression and vaccine responses. To describe markers of T cell suppression in children who do or do not receive antimalarial treatment.
Eligibility:
- Children ages 12 59 months living near Ouelessebougou in Mali. They must have no serious illness.
Design:
- Participants will be screened with medical history and physical exam.
- Some participants will get a course of antimalarial tablets. Some will not. This will be decided at random.
- Participants will have monthly visits for up to a year. They will have blood tests at each visit.
Detailed description
Malaria caused by Plasmodium falciparum continues to be a global problem with devastating consequences. New interventions are needed to combat malaria, and progress is being made in development of vaccines: a subunit vaccine called RTSS confers partial protection against clinical malaria in children and is nearing licensure; a whole organism product called PfSPZ Vaccine can confer sterile protection against infection, and is now undergoing field trials. NIAID is involved in field trials of PfSPZ Vaccine and other vaccines, and a key question in vaccine trial design has been whether concurrent parasitemia will impair vaccine responses. The primary hypothesis in this study is that T cell suppression and regulation will decrease following antimalarial treatment that clears blood stage parasites for an extended period of time.
Up to 200 children will be recruited into longitudinal studies that will be conducted in Ouelessebougou and neighboring villages in Mali. In August 2015, up to 50 children presenting for Seasonal Malaria Chemoprevention (SMC) in a village where the government has implemented SMC will be enrolled, as well as up to 50 age-matched children residing in an adjacent village where SMC has not been implemented by the government of Mali; and then followed through the rainy season. In January 2016, up to 100 healthy children in Ouelessebougou village area will be enrolled and randomized to receive or not receive a course of artemether-lumefantrine, and then followed for the duration of the dry season (Jan-Jun 2016) and the subsequent rainy season (Jul-Dec 2016). Samples in both cohort studies (age-matched SMC study; randomized artemether-lumefantrine study) will be collected from the children at the time of monthly visits and assessed in ex vivo assays for markers of T cell suppression as the primary outcome of this study. For our secondary outcomes, we will examine levels of regulatory T cells, measure T cell responses in stimulation assays, and survey parasitemia by blood smear and by polymerase chain reaction (PCR) assays. We expect that levels of T cell suppression and regulatory T cells will be similar between groups before antimalarial treatment or malaria infection, but after treatment or in those subjects that remain uninfected these levels will be significantly lower as compared to the untreated and or infected subjects.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 to 59 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- A child between 12-59 months
- Parent/guardian able to provide consent
- Resident of the health district of Ouelessebougou or neighboring district for at least a year
Key exclusion criteria (6 listed)
- Clinically symptomatic or apparent severe anemia or any other condition that may be worsened by 5 mL phlebotomy or any other study procedure
- Chronic or debilitating condition that precludes attendance for monthly visits
- Known or clinically apparent condition of immunosuppression or chronic infection.
- Known allergies to study treatments (SP; amodiaquine; artemether-lumefantrine)
- Use of cotrimaxozale on a routine basis for prophylaxis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To investigate the association of recent malaria infection and percentage of PD1+ CD4 T cells in children that have not received SMC during the rainy season.
Time frame: Approximately 3-6 months
To compare the percentage of PD1 +CD4 T cells in children who do or do not receive antimalarial treatment, in both rainy season and drythedry season.
Time frame: Approximately 3-6 months
3 secondary outcomes
To compare and describe levels of regulatory T cells in children who do or do not receive antimalarial treatment, in both rainy season and dry season. To compare and describe T cell stimulation responses in children who do or do not receive anti...
Time frame: Approximately 3-6 months
To determine and investigate phenotypic differences in T cell subsets in infected and uninfected subjects at baseline.
Time frame: Approximately 3-6 months
To confirm that blood stage parasite burden is markedly reduced throughout the dry season by a single treatment with artemether-lumefantrine at enrollment; and to examine the association of parasite clearance during the dry season on malaria ris...
Time frame: Approximately 3-6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2018.
- Background: PubMed 20370551Cunnington AJ, Riley EM. Suppression of vaccine responses by malaria: insignificant or overlooked? Expert Rev Vaccines. 2010 Apr;9(4):409-29. doi: 10.1586/erv.10.16.
- Background: PubMed 21304923Dicko A, Diallo AI, Tembine I, Dicko Y, Dara N, Sidibe Y, Santara G, Diawara H, Conare T, Djimde A, Chandramohan D, Cousens S, Milligan PJ, Diallo DA, Doumbo OK, Greenwood B. Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Mali: a randomised, double-blind, placebo-controlled trial. PLoS Med. 2011 Feb 1;8(2):e1000407. doi: 10.1371/journal.pmed.1000407.
- Background: PubMed 21340029Wilson AL; IPTc Taskforce. A systematic review and meta-analysis of the efficacy and safety of intermittent preventive treatment of malaria in children (IPTc). PLoS One. 2011 Feb 14;6(2):e16976. doi: 10.1371/journal.pone.0016976.
- Derived from this study: PubMed 31584094Attaher O, Zaidi I, Kwan JL, Issiaka D, Samassekou MB, Cisse KB, Coulibaly B, Keita S, Sissoko S, Traore T, Diarra K, Diarra BS, Dembele A, Kanoute MB, Mahamar A, Barry A, Fried M, Dicko A, Duffy PE. Effect of Seasonal Malaria Chemoprevention on Immune Markers of Exhaustion and Regulation. J Infect Dis. 2020 Jan 1;221(1):138-145. doi: 10.1093/infdis/jiz415.
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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.
Michal Fried, Ph.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
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 Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. 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: finished, as of the sponsor's last update on 14 Jun 2018. 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 Mali. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To investigate the association of recent malaria infection and percentage of PD1+ CD4 T cells in children that have not received SMC during the rainy season. (time frame: Approximately 3-6 months). 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 NCT02504918, which also lists 4 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 14 Jun 2018.