A Pilot Protocol to Determine the Effects of Chemical and Mechanical Stress on Rectal Permeability as a Surrogate for Toxicity Evaluation of Rectally Applied Microbicides
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
- Intra-subject comparison of urine and plasma concentrations of 99mTc-DTPA
研究概览
简要总结
The purpose of this study is to determine if detectable changes in permeability of the lining of the colon are caused by either application of HIV microbicide gels or medical procedures, such as flexible sigmoidoscopy.
详细描述
It is not currently known if procedures used to observe the lining of the distal colon, such as endoscopy with or without pinch biopsy, may cause mucosal trauma and thus alter colonic permeability. Additionally, the application of topical HIV microbicides (to prevent HIV transmission) and shearing forces associated with rectal intercourse might also adversely affect the epithelial layer, and thus alter colonic permeability. In order to appropriately interpret testing of the effects of topical HIV microbicides on the mucosal lining of the distal colon, it is essential to understand whether these procedures themselves, adversely affect the epithelial layer. If changes in permeability can be detected, this method may be developed to help determine microbicide distribution/toxicity in early phase studies, thus improving the selection of candidate microbicides for study in larger scale clinical trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 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
- •Greater than or equal to 21 years of age
- •Prior history of receptive anal intercourse (RAI)
- •Subjects must have a history of using commercially-available personal lubricants for RAI.
- •Ability to provide signed informed consent.
- •Willingness to abstain from lubricant use and anal receptive intercourse for 48 hours prior to and 48 hours after Phases A and B.
- •Willingness to use a single dose of rectally-applied N-9.
排除标准
- •Mental handicap or impaired cognitive performance status as judged by the investigator.
- •Coagulation abnormality which would put the subject at risk for bleeding as judged by the Principal Investigator.
- •History of anorectal surgery within the last month or the presence of any anorectal disease or condition that in the judgment of the investigator could affect permeability of the rectal mucosa.
- •Presence of any painful anorectal conditions or anorectal lesions that would be tender to manipulation.
- •History of occupational radiation exposure.
- •History of acute or chronic diarrhea defined as three or more loose stools per day.
- •History of any allergic response to rectal lubricants.
- •History of sleep apnea, or airway problems with previous sedation procedures.
- •History of significant adverse reaction to sedation medications.
研究组 & 干预措施
Normosol with simulation, endoscopy and biopsy
Normosol-R, 5 mL following simulation, endoscopy and biopsy
干预措施: Gastrointestinal instrumentation (Procedure)
Nonoxynol-9
Gynol-II, 2% N-9, 5 mL
干预措施: Nonoxynol-9 (Drug)
Normosol-R
Normosol-R, 5 mL, single administration, negative control
干预措施: Normosol-R (Drug)
Normosol with simulation, endoscopy and biopsy
Normosol-R, 5 mL following simulation, endoscopy and biopsy
干预措施: Normosol-R (Drug)
结局指标
主要结局
Intra-subject comparison of urine and plasma concentrations of 99mTc-DTPA
时间窗: 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours after introduction of the treatment assignment
次要结局
未报告次要终点
研究者
Craig W. Hendrix
Professor, Department of Medicine
Johns Hopkins University