MalariaNCT00368810
Study of Factors Involved in Resistance to Severe Malaria
An observational study of Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will examine whether resistance to severe malaria is associated with weakening of a specific immune response (TLR-mediated pro-inflammatory cytokine response). Some children with mild malaria go on to develop severe disease, while others do not. Read more about this study
- Who is it for?
- Ages 2 to 10 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Feb 2006to 30 Nov 2006
- 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 2 to 10 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Males or females ages 3 to 10.
- Severe malaria as defined by positive blood smear for P. falciparum and need for hospitalization in accordance with the WHO definition of severe malaria (group I), or mild malaria as defined by positive blood smear for P. falciparum and triage to outpatient treatment (group II).
- Willingness of parent or guardian to have his or her child participate in the study as evidenced by the completed informed consent document.
- Males or females ages 3 to 10.
- No clinical evidence of malaria and negative blood smear.
- No acute febrile or systemic illness.
- Willingness of parent or guardian to have his or her child participate in the study as evidenced by the completed informed consent document.
Who cannot join
- Active bleeding or hematocrit less than or equal to 15%.
- Participation in a vaccine or drug trial within 30 days of starting this study.
- Use of corticosteroids or immunosuppressive drugs within 30 days of starting this study.
- Receipt of a live vaccine within past 4 weeks or killed vaccine within past 2 weeks prior to entry into the study.
- Known history of HIV infection.
- Positive malaria smear.
Show all 12Show fewer
- Sibling of malaria patient.
- Active bleeding or hematocrit less than or equal to 15%.
- Participation in a vaccine or drug trial within 30 days of starting this study.
- Use of corticosteroids or immunosuppressive drugs within 30 days of starting this study.
- Receipt of a live vaccine within past 4 weeks or killed vaccine within past 2 weeks prior to entry into the study.
- Known history of HIV infection.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: Response to Plasmodium Falciparum-Derived TLR Ligands in Severe and Uncomplicated Malaria in Mali
This study will examine whether resistance to severe malaria is associated with weakening of a specific immune response (TLR-mediated pro-inflammatory cytokine response). Some children with mild malaria go on to develop severe disease, while others do not. The study will analyze certain substances in the blood to try to determine what factors may protect against severe malaria.
Healthy children and children 3 - 10 years of age with severe malaria who are being treated at l'H pital Gabriel Toure in Mamako, Mali, West Africa, may be eligible for this study. Participants have a mall sample of blood drawn from a vein and from two finger pricks.
Read the detailed description
Malaria remains an important public health threat, responsible for over two million deaths annually, the majority among African children. The mechanisms underlying resistance to the most severe manifestations of malaria remain elusive. Severe malaria has been associated with high levels of pro-inflammatory cytokines that may contribute to the pathogenesis of cerebral malaria, severe anemia and acidosis. This response is thought to be driven primarily by glycosylphosphatidylinositol (GPI) anchors derived from erythrocyte-stage Plasmodium falciparum. It has been suggested that antibodies against GPI are responsible for resistance to severe malaria, which has led to efforts to develop a GPI-based vaccine. An alternative explanation for the development of resistance to severe malaria is down regulation of the innate pro-inflammatory response by repeated ligation of toll-like receptors (TLR) by GPI, or other putative P. falciparum-derived TLR ligands, such as hemozoin. This cross-sectional study at l'Hopital Gabriel Toure in Bamako, Mali, proposes to test the hypothesis that resistance to severe malaria is associated with an attenuation of the TLR-mediated pro-inflammatory cytokine response. After informed consent is obtained from the participant's parent or guardian, 2-3 mL of venous blood will be drawn from each of 60 children: 40 children presenting with acute P. falciparum infection (20 severe and 20 uncomplicated) and 20 healthy, P. falciparum uninfected controls. The blood will be tested for antibody titers against GPI and Merozoite Surface Protein-1 (MSP-1). Peripheral blood mononuclear cells (PBMCs) will be isolated and cultured with GPI, hemozoin, lipoteichoic acid (LTA), lipopolysaccharide (LPS), and cytosine-guanine dinucleotide (CpG). At 24 hours, supernatant will be collected and the following cytokines measured: IL-1, IL-6, IL-8, IL-10, IL-12, and TNF-alpha. A clearer understanding of the responsiveness to TLR ligands in children from malaria endemic areas may provide information on potential intervention strategies such as GPI-based vaccines or the use of TLR agonists as vaccine adjuvants.
- Conditions
- Malaria
- Keywords
- Children, Cross-Sectional, Glycosylphosphatidylinositol, Cytokines, Peripheral Blood Mononuclear Cells, Malaria
- Medical subject headings
- Malaria
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2006 (estimated)
- Study start21 Feb 2006
- Study completion30 Nov 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Enrolment
- 120 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00368810
- Sponsor's protocol ID
- 999906104
- Other IDs
- 06-I-N104
- Status last verified
- 30 Nov 2006
- First submitted
- 22 Aug 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Boutlis CS, Gowda DC, Naik RS, Maguire GP, Mgone CS, Bockarie MJ, Lagog M, Ibam E, Lorry K, Anstey NM. Antibodies to Plasmodium falciparum glycosylphosphatidylinositols: inverse association with tolerance of parasitemia in Papua New Guinean children and adults. Infect Immun. 2002 Sep;70(9):5052-7. doi: 10.1128/IAI.70.9.5052-5057.2002.
PubMed 12183552
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Response to Plasmodium Falciparum-Derived TLR Ligands in Severe and Uncomplicated Malaria in Mali
- ClinicalTrials.gov ID
- NCT00368810
- Acronym / sponsor ID
- 999906104
- Conditions
- Malaria
- Keywords
- Children, Cross-Sectional, Glycosylphosphatidylinositol, Cytokines, Peripheral Blood Mononuclear Cells, Malaria
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 120 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 21 Feb 2006
- Study completion
- 30 Nov 2006
- First posted
- 25 Aug 2006 (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.
This study will examine whether resistance to severe malaria is associated with weakening of a specific immune response (TLR-mediated pro-inflammatory cytokine response). Some children with mild malaria go on to develop severe disease, while others do not. The study will analyze certain substances in the blood to try to determine what factors may protect against severe malaria.
Healthy children and children 3 - 10 years of age with severe malaria who are being treated at l'H pital Gabriel Toure in Mamako, Mali, West Africa, may be eligible for this study. Participants have a mall sample of blood drawn from a vein and from two finger pricks.
Detailed description
Malaria remains an important public health threat, responsible for over two million deaths annually, the majority among African children. The mechanisms underlying resistance to the most severe manifestations of malaria remain elusive. Severe malaria has been associated with high levels of pro-inflammatory cytokines that may contribute to the pathogenesis of cerebral malaria, severe anemia and acidosis. This response is thought to be driven primarily by glycosylphosphatidylinositol (GPI) anchors derived from erythrocyte-stage Plasmodium falciparum. It has been suggested that antibodies against GPI are responsible for resistance to severe malaria, which has led to efforts to develop a GPI-based vaccine. An alternative explanation for the development of resistance to severe malaria is down regulation of the innate pro-inflammatory response by repeated ligation of toll-like receptors (TLR) by GPI, or other putative P. falciparum-derived TLR ligands, such as hemozoin. This cross-sectional study at l'Hopital Gabriel Toure in Bamako, Mali, proposes to test the hypothesis that resistance to severe malaria is associated with an attenuation of the TLR-mediated pro-inflammatory cytokine response. After informed consent is obtained from the participant's parent or guardian, 2-3 mL of venous blood will be drawn from each of 60 children: 40 children presenting with acute P. falciparum infection (20 severe and 20 uncomplicated) and 20 healthy, P. falciparum uninfected controls. The blood will be tested for antibody titers against GPI and Merozoite Surface Protein-1 (MSP-1). Peripheral blood mononuclear cells (PBMCs) will be isolated and cultured with GPI, hemozoin, lipoteichoic acid (LTA), lipopolysaccharide (LPS), and cytosine-guanine dinucleotide (CpG). At 24 hours, supernatant will be collected and the following cytokines measured: IL-1, IL-6, IL-8, IL-10, IL-12, and TNF-alpha. A clearer understanding of the responsiveness to TLR ligands in children from malaria endemic areas may provide information on potential intervention strategies such as GPI-based vaccines or the use of TLR agonists as vaccine adjuvants.
Study design
Who may qualify
- Ages
- 2 to 10 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Males or females ages 3 to 10.
- No clinical evidence of malaria and negative blood smear.
- No acute febrile or systemic illness.
- Willingness of parent or guardian to have his or her child participate in the study as evidenced by the completed informed consent document.
Key exclusion criteria (12 listed)
- Active bleeding or hematocrit less than or equal to 15%.
- Participation in a vaccine or drug trial within 30 days of starting this study.
- Use of corticosteroids or immunosuppressive drugs within 30 days of starting this study.
- Receipt of a live vaccine within past 4 weeks or killed vaccine within past 2 weeks prior to entry into the study.
- Known history of HIV infection.
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
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 12183552Boutlis CS, Gowda DC, Naik RS, Maguire GP, Mgone CS, Bockarie MJ, Lagog M, Ibam E, Lorry K, Anstey NM. Antibodies to Plasmodium falciparum glycosylphosphatidylinositols: inverse association with tolerance of parasitemia in Papua New Guinean children and adults. Infect Immun. 2002 Sep;70(9):5052-7. doi: 10.1128/IAI.70.9.5052-5057.2002.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 United States.
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 7 inclusion and 12 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 2 Jul 2017. 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 United States. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00368810, which also lists 1 linked publication.
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 2 Jul 2017.