Immunization With Different Doses of Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis
NCT ID: NCT01218893
Last Updated: 2012-04-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
30 participants
INTERVENTIONAL
2011-04-30
2012-03-31
Brief Summary
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As a unique opportunity to study malaria immunology and efficacy of immunisation strategies, a protocol has been developed in the past to conduct experimental human malaria infections (EHMIs). EHMIs generally involve small groups of malaria-naïve volunteers infected via the bites of P. falciparum infected laboratory-reared Anopheline mosquitoes. Although potentially serious or even lethal, P. falciparum malaria can be radically cured at the earliest stages of blood infection where risks of complications are virtually absent.
The investigators have shown previously that healthy human volunteers can be protected from a malaria mosquito (sporozoite) challenge by immunization with sporozoites (by mosquito bites) under chloroquine prophylaxis (CPS immunization). However, it is unknown how many mosquito bites are necessary to confer protection. Moreover, as all volunteers were protected in this study, no correlates of protection could be established. For future development of vaccines and understanding of protective immunity to malaria, it is important to investigate the lowest dose of CPS immunization that confers 100% protection and to find correlates of protection. Therefore, the present study aims to make the CPS immunization protocol more sensitive by lowering the number of infected mosquito bites, in order to study the underlying mechanisms of protection.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
BASIC_SCIENCE
QUADRUPLE
Study Groups
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15-15-15
This group will receive three times 15 infected mosquito bites under chloroquine prophylaxis, as we know that this dose is protective.
Chloroquine prophylaxis
The chloroquine dose used will be 300mg for the first two days, followed by 300mg per week, for 13 weeks.
Immunization
All groups will be immunised with mosquitobites. The number of infected mosquitoes differs per group, as clarified in group description.
Plasmodium falciparum challenge
Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.
Malarone treatment
When thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone.
10-10-10
This group will receive three times 10 infected and 5 uninfected mosquito bites under chloroquine prophylaxis.
Chloroquine prophylaxis
The chloroquine dose used will be 300mg for the first two days, followed by 300mg per week, for 13 weeks.
Immunization
All groups will be immunised with mosquitobites. The number of infected mosquitoes differs per group, as clarified in group description.
Plasmodium falciparum challenge
Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.
Malarone treatment
When thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone.
5-5-5
This group will receive three times 5 infected and 10 uninfected mosquitobites under chloroquine prophylaxis.
Chloroquine prophylaxis
The chloroquine dose used will be 300mg for the first two days, followed by 300mg per week, for 13 weeks.
Immunization
All groups will be immunised with mosquitobites. The number of infected mosquitoes differs per group, as clarified in group description.
Plasmodium falciparum challenge
Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.
Malarone treatment
When thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone.
0-0-0
This group will receive three times 15 uninfected mosquitobites under prophylaxis.
Chloroquine prophylaxis
The chloroquine dose used will be 300mg for the first two days, followed by 300mg per week, for 13 weeks.
Immunization
All groups will be immunised with mosquitobites. The number of infected mosquitoes differs per group, as clarified in group description.
Plasmodium falciparum challenge
Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.
Malarone treatment
When thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone.
Interventions
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Chloroquine prophylaxis
The chloroquine dose used will be 300mg for the first two days, followed by 300mg per week, for 13 weeks.
Immunization
All groups will be immunised with mosquitobites. The number of infected mosquitoes differs per group, as clarified in group description.
Plasmodium falciparum challenge
Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.
Malarone treatment
When thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Good health based on history and clinical examination
* Negative pregnancy test
* Use of adequate contraception for females
* All volunteers must sign the informed consent form demonstrating their understanding of the meaning and procedures of the study
* Volunteer agrees to inform the general practitioner and agrees to sign a request to release medical information concerning contra-indications for participation in the study
* Willingness to undergo a Pf mosquito challenge
* For volunteers not living in Leiden: agreement to stay in a hotel room close to the trial center during a part of the study (Day 5 after challenge till 3 days after treatment)
* Reachable (24/7) by mobile phone during the whole study period
* Living with a third party that could contact the clinicians in case of alteration of consciousness or agreement to stay in a hotel room close to the trial center during a part of the study (Day 5 after challenge till 3 days after treatment)
* Available to attend all study visits
* Agreement to refrain from blood donation to Sanquin or for other purposes, during the study period until 337.
* Willingness to undergo HIV, hepatitis B and hepatitis C tests
* Negative urine toxicology screening test at screening visit and day before challenge
* Willingness to take a prophylactic regime of chloroquine and curative regimen of Malarone®
Exclusion Criteria
* Plans to travel to malaria endemic areas during the study period
* Plans to travel outside of the Netherlands during the challenge period
* Previous participation in any malaria vaccine study and/or positive serology for Pf
* Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers
* History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
* History of arrhythmias or prolonged QT-interval
* Positive family history in 1st and 2nd degree relatives for cardiac disease \< 50 years old
* An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system
* Clinically significant abnormalities in electrocardiogram (ECG) at screening
* Body Mass Index (BMI) below 18 or above 30 kg/m2
* Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis
* Positive HIV, HBV or HCV tests
* Participation in any other clinical study within 30 days prior to the onset of the study
* Enrollment in any other clinical study during the study period
* Pregnant or lactating women
* Volunteers unable to give written informed consent
* Volunteers unable to be closely followed for social, geographic or psychological reasons
* Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study
* A history of psychiatric disease
* Known hypersensitivity to Malarone® or chloroquine
* The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period
* Contra-indications to Malarone® or chloroquine including treatment taken by the volunteer that interferes with Malarone® or chloroquine
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia
* Co-workers of the departments of Medical Microbiology, Parasitology, or Internal Medicine of the Leiden University medical Centre
* A history of sickle cell anemia, sickle cell trait, thalassemia, thalassemia trait or G6PD deficiency
18 Years
35 Years
ALL
Yes
Sponsors
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Radboud University Medical Center
OTHER
Responsible Party
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Principal Investigators
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Leo G Visser, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Leiden University Medical Centre
Locations
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Leiden University Medical Centre
Leiden, , Netherlands
Countries
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References
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Nahrendorf W, Scholzen A, Bijker EM, Teirlinck AC, Bastiaens GJ, Schats R, Hermsen CC, Visser LG, Langhorne J, Sauerwein RW. Memory B-cell and antibody responses induced by Plasmodium falciparum sporozoite immunization. J Infect Dis. 2014 Dec 15;210(12):1981-90. doi: 10.1093/infdis/jiu354. Epub 2014 Jun 25.
Bijker EM, Teirlinck AC, Schats R, van Gemert GJ, van de Vegte-Bolmer M, van Lieshout L, IntHout J, Hermsen CC, Scholzen A, Visser LG, Sauerwein RW. Cytotoxic markers associate with protection against malaria in human volunteers immunized with Plasmodium falciparum sporozoites. J Infect Dis. 2014 Nov 15;210(10):1605-15. doi: 10.1093/infdis/jiu293. Epub 2014 May 27.
Other Identifiers
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ZonMw1
Identifier Type: -
Identifier Source: org_study_id
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