Re-exposure of EHMI-8 Human Volunteers to Live Malaria Sporozoites

NCT ID: NCT00757887

Last Updated: 2010-11-09

Study Results

Results pending

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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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-10-31

Study Completion Date

2010-08-31

Brief Summary

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In the EHMI-8 study (CMO 2006/207) the investigators induced sterile protection against P. falciparum challenge in healthy Dutch volunteers by repeated exposure to infected mosquitoes whilst under chloroquine prophylaxis. The surprisingly efficient induction of protection in this study strongly supports the development of whole parasite vaccines and is therefore an important finding to malaria vaccine development. In this study (EHMI8B) the investigators would like to explore the longevity of the protective immune response and simultaneously further characterise immune mechanisms responsible for protection by re-exposing EHMI-8 volunteers to infected mosquito bites.

Detailed Description

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Conditions

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P. Falciparum Malaria

Keywords

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malaria plasmodium falciparum human experimental infection

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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EHMI8

Previously protected volunteers, N=10

Group Type EXPERIMENTAL

Exposure to 5 P. falciparum infected mosquitoes

Intervention Type BIOLOGICAL

Five Anopheles Stephensi mosquitoes are infected with NF54 P.falciparum. volunteers are exposed to bites for 10 minutes.

control

5 malaria-naive volunteers

Group Type ACTIVE_COMPARATOR

Exposure to 5 P. falciparum infected mosquitoes

Intervention Type BIOLOGICAL

Five Anopheles Stephensi mosquitoes are infected with NF54 P.falciparum. volunteers are exposed to bites for 10 minutes.

Interventions

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Exposure to 5 P. falciparum infected mosquitoes

Five Anopheles Stephensi mosquitoes are infected with NF54 P.falciparum. volunteers are exposed to bites for 10 minutes.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Age \> 18 and \< 35 years healthy volunteers (males or females).
2. General good health based on history and clinical examination.
3. Negative pregnancy test.
4. Use of adequate contraception for females
5. All volunteers have to sign the informed consent form following proper understanding of the meaning and procedures of the study
6. Volunteer agrees to inform the general practitioner and agrees to sign a request for medical information concerning contra-indications for participation in the study
7. Willingness to undergo a P. falciparum sporozoite challenge
8. Resident near the RUNMC, Nijmegen or agree to stay in a hotel room during the intensive period of the study (Day 5 till Day T +3)
9. Reachable by mobile phone during the whole study period
10. Availability to attend all study visits
11. Agreement to refrain from blood donation to Sanquin or for other purposes, during the course of the study
12. Willingness to undergo an HIV, hepatitis B and C test
13. Negative urine toxicology screening test at screening visit and day before challenge

Exclusion Criteria

1. History of malaria other than participation in EHMI-8, or residence in malaria endemic areas within the past six months
2. Plans to travel to endemic malaria areas during the study period.
3. Only for newly recruited control volunteers: previous participation in any malaria vaccine study and/or positive serology for P. falciparum
4. 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.
5. History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
6. History of arrhythmia's or prolonged QT-interval
7. Positive family history in 1st and 2nd degree relatives of cardiac disease \< 50 years old
8. An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.
9. Any clinically significant deviation from the normal range in biochemistry or haematology blood tests or in urine analysis
10. Positive HIV, HBV or HCV tests
11. Participation in any other clinical study within 30 days prior to the onset of the study
12. Volunteers enrolled in any other clinical study during the study period
13. Pregnant or lactating women
14. Volunteers unable to give written informed consent
15. Volunteers unable to be closely followed for social, geographic or psychological reasons
16. Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study
17. A history of psychiatric disease
18. Known hypersensitivity for anti-malaria drugs
19. History of severe reactions or allergy to mosquito bites
20. The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months before study onset (inhaled and topical corticosteroids are allowed) and during the study period
21. Contra-indications to Malarone® including treatment taken by the volunteers that interfere with Malarone®
22. Any confirmed or suspected immunosuppressive or immunodeficiency condition, including asplenia
23. Co-workers of the departments of Medical Microbiology or Internal Medicine of the Radboud University Nijmegen Medical Centre
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Radboud University

Principal Investigators

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Robert Sauerwein, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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UMC St. Radboud

Nijmegen, , Netherlands

Site Status

Countries

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Netherlands

References

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Coffeng 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.

Reference Type DERIVED
PMID: 28081133 (View on PubMed)

Roestenberg M, Teirlinck AC, McCall MB, Teelen K, Makamdop KN, Wiersma J, Arens T, Beckers P, van Gemert G, van de Vegte-Bolmer M, van der Ven AJ, Luty AJ, Hermsen CC, Sauerwein RW. Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study. Lancet. 2011 May 21;377(9779):1770-6. doi: 10.1016/S0140-6736(11)60360-7. Epub 2011 Apr 22.

Reference Type DERIVED
PMID: 21514658 (View on PubMed)

Other Identifiers

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EHMI-8B

Identifier Type: -

Identifier Source: org_study_id