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MalariaNCT01422954

Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine Versus Mefloquine Prophylaxis

A study testing Chloroquine prophylaxis, Mefloquine prophylaxis and Immunization in people with Malaria and Plasmodium Falciparum, run by Radboud University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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 800.000 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
Malaria, Plasmodium Falciparum
What is being tested?
Chloroquine prophylaxis, Mefloquine prophylaxis and Immunization
Type of treatment
Vaccines
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteNetherlands
Study dates
Jan 2012to Apr 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 infection through mosquito bites
  • Agreement to stay in a hotel room close to the trial center 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 visits
  • 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 prophylactic regime of chloroquine or mefloquine 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 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 20 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: pregnancy or lactation
  • 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 or moderate or severe psychological episode in volunteer
  • A history of convulsions in volunteer
  • Severe depression, anxiety disorder of psychosis in first or second degree family
  • Contra-indications to Malarone®, chloroquine or mefloquine including hypersensitivity or treatment taken by the volunteer that interferes with Malarone®, chloroquine or mefloquine
  • 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 asplenia
  • Co-workers or trainees 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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Leiden University Medical Centre

    Leiden, 2333 ZA

Other trials in Netherlands

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 800.000 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 controlled human malaria infections (CHMIs). CHMIs 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 when 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). Interestingly, sterile protection in 100% of the human CPS immunized volunteers was achieved by a relatively miniscule dose, i.e. a total of 45 infectious mosquito bites, strikingly 20-fold more potent than the 1000 bites needed in a model using irradiated mosquitoes. One possible explanation for this efficient induction of protective immunity, is the immune modulating effect of chloroquine. The investigators aim to assess this possible immune modulating effect in CPS immunization by comparing immunization with P. falciparum sporozoites under chloroquine with immunization under mefloquine prophylaxis, which has the same antimalarial effect, but not the immune modulating effects known from chloroquine.

Being tested
Chloroquine prophylaxis, Mefloquine prophylaxis, Immunization, Controlled Human Malaria Infection, Malarone
Medical subject headings
Malaria, Malaria, Falciparum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Chloroquine prophylaxisDrug

    Standard prophylactic regime: a loading dose of 300 mg on day 14 and day 17 and then 300 mg once a week, starting on day 21, for a total duration of 13 weeks. On day 0, day 3, day 7 and day 10, this group will receive a placebo.

  • Mefloquine prophylaxisDrug

    Mefloquine prophylaxis, starting with a loading regime of split doses during the first three weeks: 125 mg on day 0, day 3, day 7, day 10, day 14 and day 17 and 250 mg once a week from day 21 onwards for a total duration of 13 weeks.

  • ImmunizationBiological

    Group 1 and 2 will receive three immunizations with Plasmodium falciparum infected mosquito-bites. Group 3 will receive an equal number of uninfected mosquito-bites.

  • Controlled Human Malaria InfectionBiological

    Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.

  • MalaroneDrug

    Also called atovaquon/proguanil

    When thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone.

Study groups in NCT01422954
Study groupRoleWhat they receive
Chloroquine immunisationActive comparatorThis group will receive chloroquine prophylaxis, and three times infected mosquito-bites.
Receives: Drug: Chloroquine prophylaxis; Biological: Immunization; Biological: Controlled Human Malaria Infection; Drug: Malarone
Mefloquine immunisationExperimentalThis group will receive mefloquine prophylaxis and infected mosquito-bites.
Receives: Drug: Mefloquine prophylaxis; Biological: Immunization; Biological: Controlled Human Malaria Infection; Drug: Malarone
Mefloquine controlPlacebo comparatorThis group will receive mefloquine prophylaxis, and uninfected mosquito-bites.
Receives: Drug: Mefloquine prophylaxis; Biological: Immunization; Biological: Controlled Human Malaria Infection; Drug: Malarone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Duration of prepatent period after challenge infection as measured by microscopy

    Measured: 21 days after challenge (day 239 of the study)

Secondary outcomes (4)

  1. Development of parasitemia as measured by PCR

    Measured: 21 days after challenge (day 239 of study)

  2. Frequency of signs or symptoms in study groups

    Measured: Day 0 - day 358 of study

  3. Cellular immune responses between study groups

    Measured: Day 0 -day 358 of study

  4. Humoral immune responses between study groups

    Measured: Day 0 - 358

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Aug 2011 (estimated)
  2. Study startJan 2012
  3. Primary completionDec 2012
  4. Study completionApr 2013

Resources

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01422954
Sponsor's protocol ID
ZonMw2
Status last verified
Apr 2013
First submitted
23 Aug 2011
Last updated
29 Apr 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Bijker EM, Schats R, Obiero JM, Behet MC, van Gemert GJ, van de Vegte-Bolmer M, Graumans W, van Lieshout L, Bastiaens GJ, Teelen K, Hermsen CC, Scholzen A, Visser LG, Sauerwein RW. Sporozoite immunization of human volunteers under mefloquine prophylaxis is safe, immunogenic and protective: a double-blind randomized controlled clinical trial. PLoS One. 2014 Nov 14;9(11):e112910. doi: 10.1371/journal.pone.0112910. eCollection 2014.

    PubMed 25396417

Questions about this trial

What is this clinical trial studying?

A study testing Chloroquine prophylaxis, Mefloquine prophylaxis and Immunization in people with Malaria and Plasmodium 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 27 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 29 Apr 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. 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 after challenge infection as measured by microscopy (time frame: 21 days after challenge (day 239 of the study)). 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 NCT01422954, 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 29 Apr 2013.

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