EVALUATION OF OPTICAL COHERENCE TOMOGRAPHY (OCT) AS A SAFETY TOOL FOR ASSESSMENT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景： 尽管为预防和治疗这一疾病作出了各种努力，但艾滋病毒仍是一种日益严重的流行病。潜在的预防方法包括杀菌剂、乳膏或凝胶，妇女可以在阴道内使用这些药物来保护她们在性交过程中免受感染。然而，杀微生物剂正在开发中，测试安全性的方法还不够敏感。在对两种潜在杀微生物剂的研究中，科学家们发现，使用这两种药物的女性比不使用这些药物的女性更容易感染艾滋病毒。早期的动物和人体研究没有预测这些药物的安全性，因此需要更灵敏的方法。光学相干断层扫描(OCT)作为一种高分辨率、非侵入性的方法被认为是一种评估阴道和宫颈衬里(上皮)的方法。在动物研究中，它可以检测阴道镜没有检测到的上皮变化，阴道镜是目前人类安全评估的金标准。 假设： 假设1：在研究剂量中，N-9将在宫颈阴道上皮中提供最小的变化。 假设2：OCT将检测阴道镜未检测到的宫颈阴道上皮的微小变化。 具体目标和程序(摘要)： 这项研究的主要目的是评估定期使用非处方药N-9是否会导致OCT可以检测到上皮毒性，但阴道镜检查不能检测到。志愿者将被随机分为两组，一组为非处方药--杀精剂在首次筛查访问后，妇女将在访问1(第0天)、访问2(第6天)和访问3(第13天)时进行OCT和阴道镜检查。治疗前后比较OCT和阴道镜检查结果。 这项研究的第二个目的是描述女性参与阴道产品安全性研究的动机和障碍，并了解女性对OCT和阴道镜检查经验的看法。这个次要目的是产生假说，因此没有提出有计划的假说。在三次录音的半结构化面试过程中，一系列开放式问题将涉及动机、障碍和认知等主题。这些定性数据的分析计划将能够确定和总结每个主题的主题。 实验设计(摘要)： 育龄妇女(18-45岁)将是这项研究的对象。他们将通过使用传单和UTMB每日公告上的研究公告以及口头宣传来招募。他们将有一个电话筛查电话，在电话中将询问有关病史的问题。符合条件的妇女将接受性传播疾病、宫颈发育不良和癌症以及怀孕的筛查。多达25名妇女将接受筛查，以招募18名妇女参加这项研究；我们预计，一些妇女将因为她们的筛查测试结果而失去资格。18名女性将进行首次就诊，接受OCT和阴道镜检查。然后，参与者将接受安慰剂(HEC)或农诺醇-9，每天两次阴道内使用，持续5.5天。参与者将在最后一剂疫苗的当天返回进行重复的OCT和阴道镜生殖器检查。在停药一周后，她将在一周后回来接受OCT和阴道镜生殖器检查。在研究过程中，她将被要求禁欲，并不得在阴道内使用其他产品。在每次访问中，她还将参加采访，探讨参与研究、使用阴道凝胶产品、接受OCT和阴道镜检查的经验。 意义(摘要)： 为了确保这些产品的安全性，需要新的方法来检测使用阴道杀微生物剂后的上皮变化。如果OCT决心检测阴道镜检查中没有注意到的变化，就像我们在动物研究中看到的那样，它有很大的潜力增强我们开发安全的阴道药物预防艾滋病毒的能力，并有可能帮助减缓这种疾病的获得率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: HIV continues to be a growing epidemic despite various efforts to prevent and treat this disease. Potential methods of prevention include microbicides, creams or gels that can be used by women inside the vagina to protect them from acquiring infections during sexual intercourse. Microbicides are being developed however, the methods to test safety are not sensitive enough. In studies of two potential microbicides, the scientists found that the women who used the medications were more susceptible to HIV than those who did not. Early animal and human studies did not predict safety in these drugs therefore more sensitive methods are needed. Optical coherence tomography (OCT) holds promise as a high resolution, non-invasive method to evaluate the lining (epithelium) of the vagina and cervix. In animal studies, it can detect epithelial changes not detected by colposcopy, the current gold standard for safety evaluation in humans. Hypotheses: Hypothesis 1: In the study dosing, N-9 will provide minimal, if any, changes in the cervicovaginal epithelium. Hypothesis 2: OCT will detect minor changes in the cervicovaginal epithelium not detected by colposcopy. Specific Aims and Procedures (summary): The primary aim of the study is to evaluate whether regular use of an over-the-counter formulation of N-9 will result in epithelial toxicity detectable by OCT but not by colposcopy. Volunteers will be randomized to use either an over-the-counter spermicide, Nonoxynol-9 (Conceptrol ) or placebo gel (Hydroxyethylcellulose - HEC, a constituent in over-the-counter vaginal medications) intravaginally twice daily for 5.5 days. After the initial screening visit, women will be evaluated by OCT and colposcopy at Visit 1 (day 0), Visit 2 (day 6) and Visit 3 (day 13). Before and after treatment, OCT and colposcopy findings will be compared. The secondary aim of the study is to describe women's motivation and barriers to potential participation in a vaginal product safety study and to understand women's perceptions of the OCT and colposcopy experience. This secondary aim is hypothesis-generating and therefore no planned hypotheses are put forth. A series of open-ended questions over the course of three audio-recorded semi-structured interviews will address the topics of motivations, barriers, and perceptions. The analytic plan for these qualitative data will enable themes to be identified and summarized for each topic. Experimental Design (summary): Reproductive-aged (18-45 years) women will be targeted for enrollment in this study. They will be recruited with the use of flyers and study announcements on the UTMB daily announcements, and by word of mouth. They will have a telephone screening call in which questions about medical history will be asked. Women who are eligible will be screened for sexually transmitted diseases, cervical dysplasia and cancer, and pregnancy. Up to twenty-five women will be screened to enroll 18 women in the study; we anticipate that some will become ineligible because of their screening test results. Eighteen women will have an initial visit in which OCT and colposcopy will be performed. The participant will then receive either placebo (HEC) or Nonoxynol-9 to be used intra-vaginally twice daily for 5.5 days. The participant will return the day of the last dose for a repeat OCT and colposcopy genital examination. She will return a week later for OCT and colposcopy genital examination after a week without medication. She will be asked to be abstinent and to use no other products in the vagina during the course of the study. At each visit, she will also participate in an interview to explore her experience with being involved in the study, using the vaginal gel product, and undergoing the examination with OCT and colposcopy. Significance (summary): New methods of detection of epithelial changes after use of vaginal microbicides are needed in order to ensure the safety of these products. If OCT is determined to detect changes not noted on colposcopy, as we have seen in animal studies, it has great potential to enhance our ability to develop safe vaginal medications for the prevention of HIV and potentially help to slow the rate of acquisition of this disease.