Plasmodium Falciparum MalariaEHMI9NCT01236612
Experimental Human Malaria Infection After Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis
A study testing Chloroquine prophylaxis, Immunization and Plasmodium falciparum Bloodstage challenge in people with Plasmodium Falciparum Malaria, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Malaria is one of the major infectious diseases in the world with a tremendous impact on the quality of life significantly contributing to the ongoing poverty in endemic countries. It causes almost one million deaths per year, the majority of which are children under the age of five. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Plasmodium Falciparum Malaria
- What is being tested?
- Chloroquine prophylaxis, Immunization and Plasmodium falciparum Bloodstage challenge
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2011to Jun 2012
- Phase
- Interventional
- 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 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age > 18 and < 35 years healthy volunteers (males or females)
- 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
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- Willingness to undergo a Pf mosquito or blood stage challenge
- For volunteers not living in Nijmegen: agreement to stay in a hotel room close to the trial center during a part of the study (for groups 1 and 3 from challenge day till 3 days after treatment, for groups 2 and 4 from 5 days 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 (for groups 1 and 3 from challenge day till 3 days after treatment, for groups 2 and 4 from 5 days 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 393
- 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®
Who cannot join
- History of malaria
- 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)
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- 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 anti-malaria drugs
- 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 or Internal Medicine of the RUNMC
- A history of sickle cell anemia, sickle cell trait, thalassemia, thalassemia trait or G6PD deficiency
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, 6500 HB
About this study
Malaria is one of the major infectious diseases in the world with a tremendous impact on the quality of life significantly contributing to the ongoing poverty in endemic countries. It causes almost one million deaths per year, the majority of which are children under the age of five. The malaria parasite enters the human body through the skin, by the bite of an infected mosquito. Subsequently, it invades the liver and develops and multiplies inside the hepatocytes. After a week, the hepatocytes burst open and the parasites are released in the blood stream, causing the clinical phase of the disease.
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, Plasmodium falciparum (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 challenge by immunization with mosquito-bites under chloroquine prophylaxis (CPS immunization). However, it is unknown whether this protection is based on immunity directed towards the liver- or the blood stage of the disease. For future development of vaccines and understanding of protective immunity to malaria, it is important to investigate at which level protective immunity is generated by CPS immunization. Therefore, we aim to investigate whether CPS immunization confers protection to a blood-stage challenge.
- Conditions
- Plasmodium Falciparum Malaria
- Being tested
- Chloroquine prophylaxis, Immunization, Plasmodium falciparum Bloodstage challenge, Plasmodium falciparum mosquito challenge, Malarone treatment
- Keywords
- Plasmodium, falciparum, malaria, chloroquine, immunity
- Medical subject headings
- Malaria, Falciparum, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chloroquine prophylaxisDrug
The chloroquine dose used will be 300mg for the first two days, followed by 300mg per week, for 13 weeks.
ImmunizationBiological
Groups 1 and 2 will be immunized with 3 times 15 bites of Pf infected mosquitoes under chloroquine prophylaxis.
Plasmodium falciparum Bloodstage challengeBiological
Groups 1 and 3 will be challenged by intravenous administration of Plasmodium falciparum infected erythrocytes.
Plasmodium falciparum mosquito challengeBiological
Groups 2 and 4 will be challenged by the bites of 5 Plasmodium falciparum infected mosquitoes.
Malarone treatmentDrug
Also called atovaquon/proguanil
When thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone.
| Study group | Role | What they receive |
|---|---|---|
| Immunization + bloodstage challenge | Experimental | Not described Receives: Drug: Chloroquine prophylaxis; Biological: Immunization; Biological: Plasmodium falciparum Bloodstage challenge; Drug: Malarone treatment |
| Immunization + mosquito challenge | Active comparator | Not described Receives: Drug: Chloroquine prophylaxis; Biological: Immunization; Biological: Plasmodium falciparum mosquito challenge; Drug: Malarone treatment |
| Control - Bloodstage challenge | Placebo comparator | Not described Receives: Biological: Plasmodium falciparum Bloodstage challenge; Drug: Malarone treatment |
| Control - Mosquito challenge | Placebo comparator | Not described Receives: Biological: Plasmodium falciparum mosquito challenge; Drug: Malarone treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of prepatent period as measured by microscopy
Measured: 21 days after challenge
Parasitemia and kinetics of parasitemia as measured by PCR
Measured: 21 days after challenge
Frequency of signs or symptoms in study groups
Measured: 21 days after challenge
Secondary outcomes (3)
Antibody production in groups 1, 2, 3 and 4
Measured: 393 days
Cellular immune response in groups 1, 2, 3 and 4
Measured: 393 days
Cytokine profile in groups 1, 2, 3 and 4
Measured: 393 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2010 (estimated)
- Study startApr 2011
- Primary completionJun 2012
- Study completionJun 2012
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 Plasmodium Falciparum MalariaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert W Sauerwein, MD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01236612
- Sponsor's protocol ID
- EHMI9
- Acronym
- EHMI9
- Status last verified
- Jan 2014
- First submitted
- 4 Nov 2010
- Last updated
- 22 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.
PubMed 19641203Bijker EM, Bastiaens GJ, Teirlinck AC, van Gemert GJ, Graumans W, van de Vegte-Bolmer M, Siebelink-Stoter R, Arens T, Teelen K, Nahrendorf W, Remarque EJ, Roeffen W, Jansens A, Zimmerman D, Vos M, van Schaijk BC, Wiersma J, van der Ven AJ, de Mast Q, van Lieshout L, Verweij JJ, Hermsen CC, Scholzen A, Sauerwein RW. Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7862-7. doi: 10.1073/pnas.1220360110. Epub 2013 Apr 18.
PubMed 23599283Coffeng LE, Hermsen CC, Sauerwein RW, de Vlas SJ. The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection. PLoS Comput Biol. 2017 Jan 12;13(1):e1005255. doi: 10.1371/journal.pcbi.1005255. eCollection 2017 Jan.
PubMed 28081133Nahrendorf 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.
PubMed 24970846
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Experimental Human Malaria Infection After Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis
- ClinicalTrials.gov ID
- NCT01236612
- Acronym / sponsor ID
- EHMI9 / EHMI9
- Conditions
- Plasmodium Falciparum Malaria
- Keywords
- Plasmodium, falciparum, malaria, chloroquine, immunity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 8 Nov 2010 (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.
Malaria is one of the major infectious diseases in the world with a tremendous impact on the quality of life significantly contributing to the ongoing poverty in endemic countries. It causes almost one million deaths per year, the majority of which are children under the age of five. The malaria parasite enters the human body through the skin, by the bite of an infected mosquito. Subsequently, it invades the liver and develops and multiplies inside the hepatocytes. After a week, the hepatocytes burst open and the parasites are released in the blood stream, causing the clinical phase of the disease.
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, Plasmodium falciparum (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 challenge by immunization with mosquito-bites under chloroquine prophylaxis (CPS immunization). However, it is unknown whether this protection is based on immunity directed towards the liver- or the blood stage of the disease. For future development of vaccines and understanding of protective immunity to malaria, it is important to investigate at which level protective immunity is generated by CPS immunization. Therefore, we aim to investigate whether CPS immunization confers protection to a blood-stage challenge.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Immunization + bloodstage challenge | Experimental | Drug: Chloroquine prophylaxis, Biological: Immunization, Biological: Plasmodium falciparum Bloodstage challenge, Drug: Malarone treatment |
| Immunization + mosquito challenge | Active comparator | Drug: Chloroquine prophylaxis, Biological: Immunization, Biological: Plasmodium falciparum mosquito challenge, Drug: Malarone treatment |
| Control - Bloodstage challenge | Placebo comparator | Biological: Plasmodium falciparum Bloodstage challenge, Drug: Malarone treatment |
| Control - Mosquito challenge | Placebo comparator | Biological: Plasmodium falciparum mosquito challenge, Drug: Malarone treatment |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Age > 18 and < 35 years healthy volunteers (males or females)
- 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
Key exclusion criteria (26 listed)
- History of malaria
- 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
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 |
|---|---|---|
| Chloroquine prophylaxisThe chloroquine dose used will be 300mg for the first two days, followed by 300mg per week, for 13 weeks. | Drug | Immunization + bloodstage challenge, Immunization + mosquito challenge |
| ImmunizationGroups 1 and 2 will be immunized with 3 times 15 bites of Pf infected mosquitoes under chloroquine prophylaxis. | Biological | Immunization + bloodstage challenge, Immunization + mosquito challenge |
| Plasmodium falciparum Bloodstage challengeGroups 1 and 3 will be challenged by intravenous administration of Plasmodium falciparum infected erythrocytes. | Biological | Control - Bloodstage challenge, Immunization + bloodstage challenge |
| Plasmodium falciparum mosquito challengeGroups 2 and 4 will be challenged by the bites of 5 Plasmodium falciparum infected mosquitoes. | Biological | Control - Mosquito challenge, Immunization + mosquito challenge |
| Malarone treatmentAlso: atovaquon/proguanilWhen thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone. | Drug | Control - Bloodstage challenge, Control - Mosquito challenge, Immunization + bloodstage challenge, Immunization + mosquito challenge |
Primary outcome
Duration of prepatent period as measured by microscopy
Time frame: 21 days after challenge
Parasitemia and kinetics of parasitemia as measured by PCR
Time frame: 21 days after challenge
Frequency of signs or symptoms in study groups
Time frame: 21 days after challenge
3 secondary outcomes
Antibody production in groups 1, 2, 3 and 4
Time frame: 393 days
Cellular immune response in groups 1, 2, 3 and 4
Time frame: 393 days
Cytokine profile in groups 1, 2, 3 and 4
Time frame: 393 days
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 22 Jan 2014.
- Background: PubMed 19641203Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.
- Results publication: PubMed 23599283Bijker EM, Bastiaens GJ, Teirlinck AC, van Gemert GJ, Graumans W, van de Vegte-Bolmer M, Siebelink-Stoter R, Arens T, Teelen K, Nahrendorf W, Remarque EJ, Roeffen W, Jansens A, Zimmerman D, Vos M, van Schaijk BC, Wiersma J, van der Ven AJ, de Mast Q, van Lieshout L, Verweij JJ, Hermsen CC, Scholzen A, Sauerwein RW. Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7862-7. doi: 10.1073/pnas.1220360110. Epub 2013 Apr 18.
- Derived from this study: PubMed 28081133Coffeng LE, Hermsen CC, Sauerwein RW, de Vlas SJ. The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection. PLoS Comput Biol. 2017 Jan 12;13(1):e1005255. doi: 10.1371/journal.pcbi.1005255. eCollection 2017 Jan.
- Derived from this study: PubMed 24970846Nahrendorf 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.
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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.
Robert W Sauerwein, MD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chloroquine prophylaxis, Immunization and Plasmodium falciparum Bloodstage challenge in people with Plasmodium Falciparum Malaria, run by Radboud University Medical Center at 1 site in Netherlands.
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 15 inclusion and 26 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 22 Jan 2014. 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 Netherlands. 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. Some participants in this study may receive a placebo. 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?
Duration of prepatent period as measured by microscopy (time frame: 21 days after challenge). The study lists 3 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 NCT01236612, 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 22 Jan 2014.