The Effect of Seminal Fluid on Distal Colon Mucosal Permeability and Susceptibility to HIV Infection
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 2
- 主要终点
- Epithelial Disruption Graded by a Pathologist Blinded to Study Intervention.
研究概览
简要总结
This research is being done to learn how seminal fluid affects the lining of the colon, and whether this might make it easier for HIV to get into the body and cause infection.
详细描述
Design of effective rectal microbicides to prevent HIV infection requires an understanding of rectal HIV transmission and the location within the lower gastrointestinal (GI) tract (luminal and mucosal) of HIV (cell-free and cell-associated) following exposure to infected seminal fluid. These basic details of HIV transmission have yet to be determined in human subjects, yet they are essential to select microbicide candidates if they are to be rationally designed to achieve effective concentrations at sites of HIV transmission. Rational development of a rectal microbicide also requires an understanding of those factors that may contribute to colonic mucosal injury - potential confounders of microbicidal effect. Such factors include exposure to seminal fluid which has been shown in animal and in vitro studies to cause histologic and permeability changes that might facilitate HIV transmission.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Able to provide signed informed consent
- •Men of 21 years or older.
- •Prior history of receptive anal intercourse.
- •Laboratory values within the last 28 days:
- •Negative for HIV antibodies
- •Lymphocyte count within normal limits
- •Neutrophil count > 1,000 cells/ml
- •Cluster of Differentiation 4 (CD4) cell count > 500 cells/ml
- •Platelet count ≥ 150,000 cells/mm3
- •Prothrombin Time (PT) within normal limits
- •Partial thromboplastin time (PTT) within normal limits.
- •No childbearing intentions.
排除标准
- •Active anorectal disease or recent (3 months) anorectal surgery;
- •Diarrhea, defined as three or more loose stools per day, for at least three days prior to admission.
- •History of sleep apnea, or airway problems with previous sedation procedures.
- •History of significant adverse reaction to sedation medications.
- •Other history, including significant occupational radiation exposure, history of inflammatory bowel disease or any other diseases and lab results, such that, in the judgment of the investigator, study procedures are not considered safe for the subject's participation.
结局指标
主要结局
Epithelial Disruption Graded by a Pathologist Blinded to Study Intervention.
时间窗: One hour
Endoscopy will be performed to obtain biopsy specimens at baseline and following each inpatient enema exposure. Samples will be obtained at each flexible sigmoidoscopy and set aside for batch sectioning and H\&E staining. Slides will be reviewed and scored by a qualified pathologist blinded to treatment assignment using a qualitative scoring system. This scoring system uses semi-quantitative scoring that focuses on acute toxicity to epithelial cell layer similar to that seen in animal studies. This is a categorical grading scale, where 0 = Epithelial surface intact;1 = \<1/3 of surface denuded; 2 = 1/3 - 2/3rds of surface denuded;3 = More than 2/3rds of surface denuded. Six separate biopsies for each subject and each treatment intervention were analyzed in a multi-level analysis. In comparison with the baseline condition (no intervention), the odds and 95% confidence interval (CI) of having a higher epithelial denudation score were calculated for each intervention.
次要结局
未报告次要终点