Re-exposure of EHMI-8 Human Volunteers to Live Malaria Sporozoites
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- A significant difference in kinetics of parasitemia between EHMI-8 and control volunteers as measured by PCR.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
- •Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study
- •A history of psychiatric disease
- •Known hypersensitivity for anti-malaria drugs
- •History of severe reactions or allergy to mosquito bites
- •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
- •Contra-indications to Malarone® including treatment taken by the volunteers that interfere with Malarone®
- •Any confirmed or suspected immunosuppressive or immunodeficiency condition, including asplenia
- •Co-workers of the departments of Medical Microbiology or Internal Medicine of the Radboud University Nijmegen Medical Centre
研究组 & 干预措施
EHMI8
Previously protected volunteers, N=10
干预措施: Exposure to 5 P. falciparum infected mosquitoes (Biological)
control
5 malaria-naive volunteers
干预措施: Exposure to 5 P. falciparum infected mosquitoes (Biological)
结局指标
主要结局
A significant difference in kinetics of parasitemia between EHMI-8 and control volunteers as measured by PCR.
时间窗: 21 days
A difference in occurrence of signs or symptoms between EHMI-8 and control volunteers
时间窗: 21 days
A significant difference in time of thick smear positivity between EHMI-8 and control volunteers
时间窗: 21 days
A significant quantitative difference in parasitemia as measured by PCR between EHMI-8 and control volunteers
时间窗: 21 days
次要结局
- Difference in immunological parameters between EHMI-8 and control volunteers.(140 days)