The Effects of Ivermectin on Human Innate Immunity Against Filarial Parasites
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded.
研究概览
简要总结
We hypothesize that ivermectin, a drug used to treat parasitic worm infections, interacts with the human innate immune system and that this contributes to its anti-parasitic effects. Participants will donate blood before and after being administered the normal human dose of the drug. We will compare the cell types present in the blood and the chemicals known to influence the human immune system before and after the drug is given, as well as measuring any changes in gene expression in white blood cells 4 and 24hrs after the drug is taken.
详细描述
Subjects will visit the University of Georgia (UGA) Clinical & Translation Research Unit (CTRU) twice on consecutive days and blood will be drawn from them. On the first occasion they will be weighed and will complete the consent process. They will have been randomly assigned to the test (Stromectol) or control (placebo) group, with 8 participants in the test group and 4 participants in the control group. Stromectol will be obtained from a medical supply distributor and a placebo will be obtained through the UGA School of Pharmacy. Drugs will be prescribed by Jonathan Murrow MD. They will be stored in their original packaging at room temperature in a drug locker in the lab at CTRU. Participants will be identified by number and allocated to groups using a block randomization protocol. Randomization and drug dispensation will be done by CTRU. Eighteen ml of blood will drawn in a fasting state and they will be administered 150 mcg/kg Stromectol or the equivalent number of placebo tablets immediately after blood is drawn. Participants will remain at CTRU for four hours after they take the drug, then another 15ml of blood will be drawn. On the second day they will attend CTRU at the same time and the third blood sample will be drawn 24 hrs after administration of the drug. On each occasion the drawn blood will be coded by CTRU staff prior to being collected by a member of the Department of Infectious Diseases and taken to the laboratory (Wildlife Health G0007) for the isolation of leukocyte populations (peripheral monocytes, lymphocytes and polymorphonuclear cells (PMNs)) and for the preparation of serum. Complete blood counts will also be carried out. Sera will be analyzed on the Luminex for cytokine/chemokine content. RNA will be isolated from the cell populations for RNASeq analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Weight over 110 pounds and under 185 pounds
排除标准
- •Pregnancy or nursing mothers.
- •Immunosuppressed individuals.
- •Hypersensitivity to ivermectin, cellulose, starch, magnesium stearate, butylated hydroxyanisole, or citric acid powder (inert ingredients of Stromectol).
- •Recent (last 3 years) travel to West or Central Africa, or any other country where onchocerciasis is present
- •Hepatitis/HIV
- •Currently taking warfarin
- •Lactose intolerance (Lactose present in placebo)
- •Currently taking Steroid medications (inhaled, oral or injection)
- •Currently taking Barbiturates, Benzodiazepines such as Xanax or Klonopin, Valproic acid (Lithium), Calcium channel blockers, Statins (cholesterol medication)
- •Liver or renal dysfunction
研究组 & 干预措施
Ivermectin
Ivermectin will be administered once at 150mcg/kg, orally.
干预措施: Ivermectin (Drug)
Control
An oral placebo will be administered once
干预措施: Placebo (Other)
结局指标
主要结局
The Number of Cytokines Showing Statistically Significant Changes From Pre-treatment Levels Will be Recorded.
时间窗: Pre-treatment, 4 hours and 24 hours post-treatment
Changes in serum levels of a panel of 41 cytokines will be compared to baseline levels using Luminex methods (HCYTOMAG-60K-PX41 kit from EMD Millipore). No pre-specified threshold was set for biological significance, and the number of cytokines showing a statistically significant (p=\<0.05) change from time 0 for each group will be reported. The number of cytokines with significant changes is taken from a comparison of the mean levels in each of the groups, not at the level of individual participants.
Number of Transcripts in PBMC With Statistically Significant Changes From Pre-treatment Levels.
时间窗: Pre-treatment, 4 hours and 24 hours post-treatment
Changes in expression levels of approximately 770 genes involved in innate immunity will be measured in peripheral blood mononuclear cells (PBMC) before and after treatment. The number of transcripts with significant changes is taken from a comparison of the mean levels in each of the groups, not at the individual participant level. No pre-determined threshold was set for the biological significance of these changes.
次要结局
- Complete Blood Counts (CBC)(Pre-treatment (0hrs), 24 hours)
研究者
Adrian Wolstenholme
Professor
University of Georgia