Malaria, FalciparumTIP4NCT01660854
Re-exposure of Human Volunteers to a Heterologous Strain of P. Falciparum Sporozoites
A study testing Heterologous challenge and Malarone treatment in people with Malaria, Falciparum, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
In a previous study (NL33904.091.10) the investigators challenged 24 volunteers after Chloroquine Prophylaxis Sporozoites (CPS) immunization with 45, 30 or 15 infected mosquito-bites respectively. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Falciparum
- What is being tested?
- Heterologous challenge and Malarone treatment
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteNetherlands
- Study dates
- Jul 2012to Jan 2013
- 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
- Signing of the informed consent form, thereby demonstrating understanding of the meaning and procedures of the study
- Agreement to inform the general practitioner and 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 controlled challenge through mosquito bites
- Agreement to stay in a hotel room close to the trial centre during a part of the study (Day 5 after challenge till treatment is finished)
- Reachable (24/7) by mobile phone during the whole study period
- Available to attend all study visit
- Agreement to refrain from blood donation to Sanquin or for other purposes, during the whole study period
- Willingness to undergo HIV, hepatitis B and hepatitis C tests
- Negative urine toxicology screening test at screening visit and the day before challenge
- Willingness to take a curative regimen of Malarone®
Who cannot join
- History of malaria (other than participation in ZonMw1 study) or residence in malaria endemic areas within the past six months
- 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 (except ZonMw1 volunteers)
- 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 events < 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
- For women: being pregnant or lactating
- Volunteers unable to give written informed consent
- Volunteers unable to be closely followed for social, geographic or psychological reasons
- History of drug or alcohol abuse interfering with normal social function
- A history of treatment for psychiatric disease
- A history of convulsions
- Contra-indications to Malarone®, including hypersensitivity or treatment taken by the volunteer that interferes with Malarone®
- The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids and oral anti-histaminic are allowed) and during the study period
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including (functional) asplenia
- Co-workers or trainees of the departments Infectious Diseases, Medical Microbiology or Parasitology of the Leiden University Medical Centre (LUMC) or Medical Microbiology, Parasitology, Radboud University Nijmegen (RUNMC)
- A history of sickle cell anaemia, sickle cell trait, thalassaemia (or trait), G6PD deficiency
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Re-exposure of Previously Immunized and Challenged Human Volunteers to a Heterologous Strain of P. Falciparum Sporozoites
In a previous study (NL33904.091.10) the investigators challenged 24 volunteers after Chloroquine Prophylaxis Sporozoites (CPS) immunization with 45, 30 or 15 infected mosquito-bites respectively. The availability of this immunized cohort opens the unique opportunity to determine protection to a heterologous challenge for both of the protected and unprotected volunteers as the previous challenge infection might have served as immunological boost to the unprotected volunteers.
In the current observational, proof of principle study, the investigators aim to investigate the protection on an individual basis of these previously immunized and challenged volunteers against a heterologous P. falciparum challenge.
- Conditions
- Malaria, Falciparum
- Being tested
- Heterologous challenge, Malarone treatment
- Keywords
- Plasmodium, falciparum, malaria, heterologous, 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.
Heterologous challengeBiological
challenge by the bites of 5 Plasmodium falciparum infected mosquitoes.
Malarone treatmentDrug
Also called atovaquon/proguanil
Three days: 4 tablets 250/100mg per day
| Study group | Role | What they receive |
|---|---|---|
| Heterologous challenge | Experimental | Biological: Heterologous challenge with 5 infected mosquito bites (NF135) after previous CPS immunization and challenge.
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.
Other Name: atovaquone/proguanil Receives: Biological: Heterologous challenge; Drug: Malarone treatment |
| Challenge control | Active comparator | Biological: Plasmodium falciparum mosquito challenge by the bites of 5 Plasmodium falciparum infected mosquitoes (NF135).
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.
Other Name: atovaquone/proguanil Receives: Biological: Heterologous 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 after challenge infection as measured by microscopy
Measured: 21 days after challenge
Secondary outcomes (3)
• 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
• Immune responses between study groups
Measured: 21 days after challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2012 (estimated)
- Study startJul 2012
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malaria, FalciparumStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center
- Responsible party
- Sponsor
- Investigators
- RW Sauerwein, PhD, Study director, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01660854
- Sponsor's protocol ID
- TIP4
- Acronym
- TIP4
- Status last verified
- Jul 2012
- First submitted
- 23 Jul 2012
- Last updated
- 13 Feb 2013
- 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 19641203Schats R, Bijker EM, van Gemert GJ, Graumans W, van de Vegte-Bolmer M, van Lieshout L, Haks MC, Hermsen CC, Scholzen A, Visser LG, Sauerwein RW. Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites. PLoS One. 2015 May 1;10(5):e0124243. doi: 10.1371/journal.pone.0124243. eCollection 2015.
PubMed 25933168
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Re-exposure of Previously Immunized and Challenged Human Volunteers to a Heterologous Strain of P. Falciparum Sporozoites
- ClinicalTrials.gov ID
- NCT01660854
- Acronym / sponsor ID
- TIP4 / TIP4
- Conditions
- Malaria, Falciparum
- Keywords
- Plasmodium, falciparum, malaria, heterologous, immunity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Leiden University Medical Center
- Study start
- Jul 2012
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 9 Aug 2012 (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.
In a previous study (NL33904.091.10) the investigators challenged 24 volunteers after Chloroquine Prophylaxis Sporozoites (CPS) immunization with 45, 30 or 15 infected mosquito-bites respectively. The availability of this immunized cohort opens the unique opportunity to determine protection to a heterologous challenge for both of the protected and unprotected volunteers as the previous challenge infection might have served as immunological boost to the unprotected volunteers.
In the current observational, proof of principle study, the investigators aim to investigate the protection on an individual basis of these previously immunized and challenged volunteers against a heterologous P. falciparum challenge.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Heterologous challenge | Experimental | Biological: Heterologous challenge, Drug: Malarone treatmentBiological: Heterologous challenge with 5 infected mosquito bites (NF135) after previous CPS immunization and challenge. Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone. Other Name: atovaquone/proguanil |
| Challenge control | Active comparator | Biological: Heterologous challenge, Drug: Malarone treatmentBiological: Plasmodium falciparum mosquito challenge by the bites of 5 Plasmodium falciparum infected mosquitoes (NF135). Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone. Other Name: atovaquone/proguanil |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 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
- Signing of the informed consent form, thereby demonstrating understanding of the meaning and procedures of the study
Key exclusion criteria (26 listed)
- History of malaria (other than participation in ZonMw1 study) or residence in malaria endemic areas within the past six months
- 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 (except ZonMw1 volunteers)
- 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 |
|---|---|---|
| Heterologous challengechallenge by the bites of 5 Plasmodium falciparum infected mosquitoes. | Biological | Challenge control, Heterologous challenge |
| Malarone treatmentAlso: atovaquon/proguanilThree days: 4 tablets 250/100mg per day | Drug | Challenge control, Heterologous challenge |
Primary outcome
Duration of prepatent period after challenge infection as measured by microscopy
Time frame: 21 days after challenge
3 secondary outcomes
• 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
• Immune responses between study groups
Time frame: 21 days after challenge
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 13 Feb 2013.
- 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.
- Derived from this study: PubMed 25933168Schats R, Bijker EM, van Gemert GJ, Graumans W, van de Vegte-Bolmer M, van Lieshout L, Haks MC, Hermsen CC, Scholzen A, Visser LG, Sauerwein RW. Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites. PLoS One. 2015 May 1;10(5):e0124243. doi: 10.1371/journal.pone.0124243. eCollection 2015.
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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.
RW Sauerwein, PhD study director
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 Heterologous challenge and Malarone treatment in people with Malaria, Falciparum, 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 14 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 13 Feb 2013. 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. 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 after challenge infection as measured by microscopy (time frame: 21 days after challenge). 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 NCT01660854, which also lists 2 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 13 Feb 2013.