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

NCT00757887 | Completed DMC

• 1 other identifier: EHMI-8B
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

P. Falciparum Malaria

Keywords

malaria; plasmodium; falciparum; human; experimental infection

Outcome Measures

Primary Outcomes (4)

• A significant difference in time of thick smear positivity between EHMI-8 and control volunteers

  21 days

• A significant quantitative difference in parasitemia as measured by PCR between EHMI-8 and control volunteers

  21 days

• A significant difference in kinetics of parasitemia between EHMI-8 and control volunteers as measured by PCR.

  21 days

• A difference in occurrence of signs or symptoms between EHMI-8 and control volunteers

  21 days

Secondary Outcomes (1)

• Difference in immunological parameters between EHMI-8 and control volunteers.

  140 days

Study Arms (2)

EHMI8

EXPERIMENTAL

Previously protected volunteers, N=10

Biological: Exposure to 5 P. falciparum infected mosquitoes

control

ACTIVE COMPARATOR

5 malaria-naive volunteers

Biological: Exposure to 5 P. falciparum infected mosquitoes

Interventions

Exposure to 5 P. falciparum infected mosquitoes BIOLOGICAL

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

EHMI8; control

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age \> 18 and \< 35 years healthy volunteers (males or females).
• General good health based on history and clinical examination.
• Negative pregnancy test.
• Use of adequate contraception for females
• All volunteers have to sign the informed consent form following proper understanding of the meaning and procedures of the study
• Volunteer agrees to inform the general practitioner and agrees to sign a request for medical information concerning contra-indications for participation in the study
• Willingness to undergo a P. falciparum sporozoite challenge
• 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)
• Reachable by mobile phone during the whole study period
• Availability to attend all study visits
• Agreement to refrain from blood donation to Sanquin or for other purposes, during the course of the study
• Willingness to undergo an HIV, hepatitis B and C test
• Negative urine toxicology screening test at screening visit and day before challenge

You may not qualify if:

• History of malaria other than participation in EHMI-8, or residence in malaria endemic areas within the past six months
• Plans to travel to endemic malaria areas during the study period.
• Only for newly recruited control volunteers: previous participation in any malaria vaccine study and/or positive serology for P. falciparum
• 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 arrhythmia's or prolonged QT-interval
• Positive family history in 1st and 2nd degree relatives of 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.
• Any clinically significant deviation from the normal range in biochemistry or haematology 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
• Volunteers enrolled 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

UMC St. Radboud

Nijmegen, 6500 HB, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 28081133 DERIVED

• 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.

  PMID: 21514658 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Robert Sauerwein, Prof. Dr.

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 22, 2008
• First Posted: September 23, 2008
• Study Start: October 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: November 9, 2010

Record last verified: 2009-10

Locations

NL (1)