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

P. Falciparum Malaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00757887
• Other study ID #: EHMI-8B
• Status: Completed
• Phase: N/A
• First received: September 22, 2008
• Last updated: November 8, 2010
• Start date: October 2009
• Est. completion date: August 2010

Study information

• Verified date: October 2009
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Dutch Health Care Inspectorate
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• P. Falciparum Malaria

Intervention

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.

Locations

Country	Name	City	State
Netherlands	UMC St. Radboud	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	A significant difference in time of thick smear positivity between EHMI-8 and control volunteers		21 days	No
Primary	A significant quantitative difference in parasitemia as measured by PCR between EHMI-8 and control volunteers		21 days	No
Primary	A significant difference in kinetics of parasitemia between EHMI-8 and control volunteers as measured by PCR.		21 days	No
Primary	A difference in occurrence of signs or symptoms between EHMI-8 and control volunteers		21 days	No
Secondary	Difference in immunological parameters between EHMI-8 and control volunteers.		140 days	No

External Links

•   Dutch description of study for recruitment purposes