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

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00757887
First received: September 22, 2008
Last updated: November 8, 2010
Last verified: October 2009
  Purpose

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.


Condition Intervention
P. Falciparum Malaria
Biological: Exposure to 5 P. falciparum infected mosquitoes

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Re-exposure of EHMI-8 Human Volunteers to Live Malaria Sporozoites

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • A significant difference in time of thick smear positivity between EHMI-8 and control volunteers [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • A significant quantitative difference in parasitemia as measured by PCR between EHMI-8 and control volunteers [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • A significant difference in kinetics of parasitemia between EHMI-8 and control volunteers as measured by PCR. [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • A difference in occurrence of signs or symptoms between EHMI-8 and control volunteers [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Difference in immunological parameters between EHMI-8 and control volunteers. [ Time Frame: 140 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: October 2009
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EHMI8
Previously protected volunteers, N=10
Biological: 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.
Active Comparator: control
5 malaria-naive volunteers
Biological: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00757887

Locations
Netherlands
UMC St. Radboud
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Robert Sauerwein, Prof. Dr. Radboud University
  More Information

Additional Information:
No publications provided by Radboud University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Dr. R.W. Sauerwein, Radboud University
ClinicalTrials.gov Identifier: NCT00757887     History of Changes
Other Study ID Numbers: EHMI-8B
Study First Received: September 22, 2008
Last Updated: November 8, 2010
Health Authority: Netherlands: Dutch Health Care Inspectorate

Keywords provided by Radboud University:
malaria
plasmodium
falciparum
human
experimental infection

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on August 28, 2014