MalariaNCT02544048
Markers of T Cell Suppression: Antimalarial Treatment and Vaccine Responses in Healthy Malian Adults
An observational study of Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
Trial summary
Background: People with malaria often show altered immune responses to many illnesses and vaccines. This means that the malaria might cause immune suppression. It is not clear how or which vaccines are impacted by malaria. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- How many people
- 49 participants
- Where
- 1 siteMali
- Study dates
- 4 Sep 2015to 11 Aug 2017
- 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 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Enrolled, completed unblinding, and have opted to receive the comparator vaccines in either NIAID Protocol 13-I-N109 or 15-I-0044
- In good general health and without any clinically significant medical history
- Willing to have blood samples stored for future research
- Known resident of Bancoumana or surrounding area
Who cannot join
- Known to be pregnant (by history)
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, psychiatric, or renal disease by history and/or physical examination
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol
- Prior to Study Day 0, receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks
- Use of chronic (greater than or equal to 14 days) oral or intravenous corticosteroids (excluding topical or nasal) at immunosuppressive doses (eg, prednisone > 10 mg/day) or immunosuppressive drugs within 30 days of Study Day 0
- Known allergies or contraindications to study treatment (Coartem [artemether//lumefantrine]) or vaccines (Euvax B or TWINRIX and Menactra )
- Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial, interfere with the evaluation of the study objectives, or would render the subject unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Background:
People with malaria often show altered immune responses to many illnesses and vaccines. This means that the malaria might cause immune suppression. It is not clear how or which vaccines are impacted by malaria. It is also not clear if the impacts are such that people should be preemptively treated before they get vaccinations. Researchers want to see if there is a link between taking an antimalaria drug prior to getting vaccines and the immune response to those vaccines. To do this, they will study people who are taking part in certain NIAID studies.
Read more
Objectives:
To compare the proportion of PD1+ CD4 T cells among all T cells in vaccine immune responses in adults who have or have not received antimalarials prior to getting a Menactra vaccine.
Eligibility:
Healthy Malian adults who:
Were previously enrolled in NIAID Protocol 13-I-N109 or 15-I-0044
Reside in Bancoumana and neighboring villages
Are not pregnant
Design:
Participants will be screened with a physical exam.
Participants will get the vaccines listed below as part of Protocol 13-I-N109 or 15-I-0044. This study will follow their schedule.
At each visit, participants will give a blood sample. They will also have a physical exam. Each visit will last 1 to 2 hours.
At visit 1, participants will get a hepatitis vaccine.
Two weeks later, participants may get the antimalarial drug Coartem . They will be chosen at random.
Two weeks later, participants will get Menactra .
Participants will have 5 follow-up visits after they get Menactra .
The study will last up to 4 months.
...
Read the detailed description
Malaria patients often show altered immune responses, not only to malaria parasites but also to unrelated pathogens (eg, HIV, EBV, salmonella, helminthes) and antigens, including routine vaccines, suggesting that there is an active immune suppression or more accurately perhaps, immunomodulation, occurring during the course of malaria infection. How and which vaccines are impacted by clinical malaria or asymptomatic parasitemia is not completely clear and nor is whether the impacts are significant enough to recommend delaying or pre-emptively treating individuals prior to vaccinations.
Up to 75 adults will be recruited from volunteers enrolled in NIAID protocol 13-I-N109 and NIAID protocol 15-I-0044 who after unblinding have opted to receive or complete the comparator vaccine series: Euvax (Hepatitis B) or TWINRIX (Hepatitis B) and Menactra (Meningococcal). This longitudinal study will be conducted in Bancoumana and neighboring villages in Mali. In September 2015, up to 50 adults presenting for their Vaccination #3 of Euvax will be enrolled from NIAID protocol 13-I-N109. In October 2015, up to 25 adults presenting for their Study Day 168 will be enrolled following unblinding from NIAID protocol 15-I-0044.
Following receipt of their Euvax B or TWINRIX vaccination, subjects will be randomized to receive or not receive a course of Coartem (artemether-lumefantrine) 2 weeks prior to their scheduled Menactra vaccination. They will then be followed for approximately 3 months post receipt of Menactra . Samples will be collected from the adults at the time of prior to and following receipt of both vaccinations 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 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
- Immune, Parasitemia, Menactra, Polymerase Chain Reaction (PCR), Coartem
- Medical subject headings
- Malaria, Parasitemia
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of T cells expressing PD-1 among all T cells on Study Day 42
Measured: Study Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2015 (estimated)
- Study start4 Sep 2015
- Primary completion4 Sep 2015
- Study completion11 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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
- 49 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sara A Healy, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02544048
- Sponsor's protocol ID
- 999915197
- Other IDs
- 15-I-N197
- Status last verified
- 11 Aug 2017
- First submitted
- 5 Sep 2015
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Williamson WA, Greenwood BM. Impairment of the immune response to vaccination after acute malaria. Lancet. 1978 Jun 24;1(8078):1328-9. doi: 10.1016/s0140-6736(78)92403-0.
PubMed 78096Cunnington 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 20370551Greenwood BM, Bradley-Moore AM, Bryceson AD, Palit A. Immunosuppression in children with malaria. Lancet. 1972 Jan 22;1(7743):169-72. doi: 10.1016/s0140-6736(72)90569-7. No abstract available.
PubMed 4109547
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Markers of T Cell Suppression: Antimalarial Treatment and Vaccine Responses in Healthy Malian Adults
- ClinicalTrials.gov ID
- NCT02544048
- Acronym / sponsor ID
- 999915197
- Conditions
- Malaria
- Keywords
- Immune, Parasitemia, Menactra, Polymerase Chain Reaction (PCR), Coartem
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 4 Sep 2015
- Primary completion
- 4 Sep 2015 (actual)
- Study completion
- 11 Aug 2017 (actual)
- First posted
- 9 Sep 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:
People with malaria often show altered immune responses to many illnesses and vaccines. This means that the malaria might cause immune suppression. It is not clear how or which vaccines are impacted by malaria. It is also not clear if the impacts are such that people should be preemptively treated before they get vaccinations. Researchers want to see if there is a link between taking an antimalaria drug prior to getting vaccines and the immune response to those vaccines. To do this, they will study people who are taking part in certain NIAID studies.
Objectives:
To compare the proportion of PD1+ CD4 T cells among all T cells in vaccine immune responses in adults who have or have not received antimalarials prior to getting a Menactra vaccine.
Eligibility:
Healthy Malian adults who:
Were previously enrolled in NIAID Protocol 13-I-N109 or 15-I-0044
Reside in Bancoumana and neighboring villages
Are not pregnant
Design:
Participants will be screened with a physical exam.
Participants will get the vaccines listed below as part of Protocol 13-I-N109 or 15-I-0044. This study will follow their schedule.
At each visit, participants will give a blood sample. They will also have a physical exam. Each visit will last 1 to 2 hours.
At visit 1, participants will get a hepatitis vaccine.
Two weeks later, participants may get the antimalarial drug Coartem . They will be chosen at random.
Two weeks later, participants will get Menactra .
Participants will have 5 follow-up visits after they get Menactra .
The study will last up to 4 months.
...
Detailed description
Malaria patients often show altered immune responses, not only to malaria parasites but also to unrelated pathogens (eg, HIV, EBV, salmonella, helminthes) and antigens, including routine vaccines, suggesting that there is an active immune suppression or more accurately perhaps, immunomodulation, occurring during the course of malaria infection. How and which vaccines are impacted by clinical malaria or asymptomatic parasitemia is not completely clear and nor is whether the impacts are significant enough to recommend delaying or pre-emptively treating individuals prior to vaccinations.
Up to 75 adults will be recruited from volunteers enrolled in NIAID protocol 13-I-N109 and NIAID protocol 15-I-0044 who after unblinding have opted to receive or complete the comparator vaccine series: Euvax (Hepatitis B) or TWINRIX (Hepatitis B) and Menactra (Meningococcal). This longitudinal study will be conducted in Bancoumana and neighboring villages in Mali. In September 2015, up to 50 adults presenting for their Vaccination #3 of Euvax will be enrolled from NIAID protocol 13-I-N109. In October 2015, up to 25 adults presenting for their Study Day 168 will be enrolled following unblinding from NIAID protocol 15-I-0044.
Following receipt of their Euvax B or TWINRIX vaccination, subjects will be randomized to receive or not receive a course of Coartem (artemether-lumefantrine) 2 weeks prior to their scheduled Menactra vaccination. They will then be followed for approximately 3 months post receipt of Menactra . Samples will be collected from the adults at the time of prior to and following receipt of both vaccinations 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 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
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Enrolled, completed unblinding, and have opted to receive the comparator vaccines in either NIAID Protocol 13-I-N109 or 15-I-0044
- In good general health and without any clinically significant medical history
- Willing to have blood samples stored for future research
- Known resident of Bancoumana or surrounding area
Key exclusion criteria (7 listed)
- Known to be pregnant (by history)
- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, psychiatric, or renal disease by history and/or physical examination
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol
- Prior to Study Day 0, receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks
- Use of chronic (greater than or equal to 14 days) oral or intravenous corticosteroids (excluding topical or nasal) at immunosuppressive doses (eg, prednisone > 10 mg/day) or immunosuppressive drugs within 30 days of Study Day 0
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
Proportion of T cells expressing PD-1 among all T cells on Study Day 42
Time frame: Study Day 42
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 17 Dec 2019.
- Background: PubMed 78096Williamson WA, Greenwood BM. Impairment of the immune response to vaccination after acute malaria. Lancet. 1978 Jun 24;1(8078):1328-9. doi: 10.1016/s0140-6736(78)92403-0.
- 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 4109547Greenwood BM, Bradley-Moore AM, Bryceson AD, Palit A. Immunosuppression in children with malaria. Lancet. 1972 Jan 22;1(7743):169-72. doi: 10.1016/s0140-6736(72)90569-7. No abstract available.
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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.
Sara A Healy, M.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 7 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 17 Dec 2019. 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?
Proportion of T cells expressing PD-1 among all T cells on Study Day 42 (time frame: Study Day 42). 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 NCT02544048, which also lists 3 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 17 Dec 2019.