Repeated Controlled Human Hookworm Infection in Healthy Dutch Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Magnitude of adverse events
研究概览
简要总结
Twenty-four healthy hookworm-naive volunteers will be exposed to 50 L3 Necator americanus larvae for a maximum of three times.
详细描述
Twenty-four volunteers will be allocated equally into three groups (i.e. group A, B, C). Group A, B, and C will have one, two, and three infections respectively. Every infection will be performed with 50 L3 Necator americanus larvae. Group A will receive infection at week 4 only. Group B will be infected at week 2 and week 4. Group C will be infected at week 0, 2 and 4. To maintain blinding, group A and B will receive mock infections with water at week 0 and week 0 and 2 respectively. The interval between each CHHI is 2 weeks. Before every infection, the safety will be assessed by a review of adverse events data with a local safety monitor.
Sixteen weeks after the last infection (week 20), all volunteers will be offered treatment with a 3-day regimen of albendazole to abrogate infection. Volunteers with average egg counts >250 eggs per gram will be asked if they would be willing to keep their infection for a maximum of two years (chronic donors). No more than four volunteers will be selected to be chronic donors. Six months after the last infection (or after the last donation for the chronic donors) volunteers will undergo their last visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject is aged ≥ 18 and ≤ 45 years and in good health.
- •Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
- •Subject is able to communicate well with the investigator, is available to attend all study visits.
- •Subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period.
- •For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
- •Subject has signed informed consent.
排除标准
- •Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immune-deficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following:
- •Body Mass Index (BMI) <18.0 or >30.0 kg/m2 at screening;
- •positive HIV, HBV or HCV screening tests;
- •the use of immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period;
- •having one of the following laboratory abnormalities: ferritine <10 ug/L, transferrine <2.04 g/L or Hb <7.0 mmol/L for females or <8.0 mmol/L for males;
- •history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years;
- •any history of treatment for severe psychiatric disease by a psychiatrist in the past year;
- •history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.
- •Known hypersensitivity to or contra-indications for use of albendazole, including co-medication known to interact with albendazole metabolism (e.g. carbamazepine, phenobarbital, phenytoin, cimetidine, theophylline, dexamethasone)
- •Known allergy to amphotericin B or gentamicin
- •For female subjects: positive urine pregnancy test at screening
- •Positive faecal qPCR or Kato-Katz for hookworm at screening, any known history of hookworm infection or treatment for hookworm infection or possible exposure to hookworm in the past
- •Being an employee or student of the department of parasitology of the LUMC
- •Current or past scars, tattoos, or other disruptions of skin integrity at the intended site of larval application
- •Subjects with planned travel to hookworm endemic areas during this trial
- •Receipt of a vaccine within 4 weeks prior to the study initiation
- •Known food allergy
结局指标
主要结局
Magnitude of adverse events
时间窗: 28 weeks
Magnitude of adverse events as compared between study groups A, B and C.
Frequency of adverse events
时间窗: 28 weeks
Frequency of adverse events as compared between study groups A, B and C.
次要结局
- Variability in egg secretion(20 weeks)
- Lowest dose at which there is 100% patent hookworm infection(20 weeks)
- Comparison of the average number of eggs secreted(20 weeks)
研究者
Meta Roestenberg
Principal Investigator
Leiden University Medical Center