Comparison of Early and Late Administration of Doxycycline in Their Efficacy Against Mansonella Perstans and in Development of Immunity Against Mycobacterial Infections
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Microfilarial assessment
研究概览
简要总结
This study will determine the influence of doxycycline treatment against Wolbachia/M. perstans on immunity against concomitant mycobacterial infections in healthy M. perstans infected individuals. In this regard, the investigators will perform a community-based randomized controlled trial (Phase 2a) in Asante Akim North District. A cohort of 200 participants who are contacts of patients with Tuberculosis or Buruli ulcer, of both sexes with no clinical condition requiring long-term medication but connected with Mansonella perstans will be investigated for the effect of doxycycline on microfilaria, the immune response and development of mycobacterial disease.
详细描述
The purpose of this study is to describe the immune response to Mansonella perstans with or without doxycycline treatment. And to suggest the use of doxycycline for the treatment of Mansonella perstans infected individuals. Two hundred Mansonella perstans infected individuals who are contacts of patients with Buruli ulcer or Tuberculosis will be recruited and placed in two groups. Hundred patients in each group ('early', or 'delayed' doxycycline-treatment group) with weight 40kg and above. Individuals will be recruited from communities in the Asante Akim North District.
Half of the M. perstans infected individuals (randomly selected) will be treated immediately with 200mg daily doxycycline for six weeks. All recruited individuals will be asked to donate 20ml; 10 ml heparinized blood, 5ml Ethylenediaminetetraacetic acid blood and 5ml blood for serum analysis at baseline (day 0), after 4 months (day 112), after 12 months (day 336) and after 24 months (day 672). Six months after doxycycline treatment for M. perstans infected individuals the other 100 patients who are not treated at time point 0 (delayed' treatment group) will be treated as described for the 'early' treatment group. After four months (day 112) individuals from both treatment groups will be asked to donate blood for quantitative Polymerase Chain Reaction to confirm Wolbachia depletion and immunological analyses.
For 'early', and 'delayed', doxycycline-treatment group immunological assays will be performed at days 0, 112, 336 and 672 after treatment initiation for all recruited individuals.
Hypothesis:
Presence of filarial nematodes Mansonella perstans will polarize the host immunity towards humoral and T helper type 2-mediated immunity and treatment with doxycycline will result in killing of Wolbachia endosymbionts, depletion of Mansonella perstans and development of a T helper type 1 immunity and reduced risk of developing Tuberculosis and Buruli ulcer
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 9 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •M. perstans mg-positive status Good general health without any clinical condition requiring long-term medication.
- •Normal renal and hepatic laboratory profiles
排除标准
- •Known intolerance to the doxycycline Body weight <40 kg Pregnancy or breastfeeding History of severe allergic reaction or anaphylaxis Alcohol or drug abuse
研究组 & 干预措施
Early doxycycline administered
Early doxycycline administered - volunteers will be treated immediately with 200mg daily doxycycline for 6 weeks
干预措施: Doxycycline (Drug)
Delayed doxycycline administered
Delayed doxycycline administered-volunteers will be treated six months after the early group has received treatment with 200mg daily doxycycline for 6 weeks
干预措施: Doxycycline (Drug)
结局指标
主要结局
Microfilarial assessment
时间窗: Change from baseline microfilarial load at 12 months
Assessment of the microfilarial load
次要结局
- Demonstrate development of a T helper type 1 immunity through Immunological profile of cellular immune responses(Change from baseline T helper type 1 cytokine levels at 24 weeks)
研究者
Dr Richard Phillips
Dr
Kwame Nkrumah University of Science and Technology