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

光学相干断层扫描 (OCT) 作为安全评估工具的评估

• 批准号: 7952177
• 负责人: Susan L Rosenthal
• 金额: $ 0.27万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952177
• 关键词: AIDS prevention; Address; Aftercare; Age; Animals; Cervical dysplasia; Cervix Uteri; Clinical Research; Coitus; Colposcopy; Computer Retrieval of Information on Scientific Projects Database; Conceptrol; Cream; Data; Detection; Disease; Dose; Drug Formulations; Enrollment; Ensure; Epidemic; Epithelial; Epithelium; Evaluation; Experimental Designs; Funding; Gel; Genital system; Gold; Grant; HIV; Human; Infection; Institution; Interview; Malignant Neoplasms; Medical History; Methods; Minor; Motivation; Nonoxynol 9; Optical Coherence Tomography; Oral cavity; Participant; Perception; Pharmaceutical Preparations; Placebos; Pregnancy; Prevention; Procedures; Randomized; Recruitment Activity; Research; Research Personnel; Resolution; Resources; Safety; Scientist; Screening procedure; Series; Sexually Transmitted Diseases; Source; Spermatocidal Agents; Structure; Telephone; Test Result; Toxic effect; United States National Institutes of Health; Vagina; Vaginal Gel; Visit; Woman; experience; hydroxyethylcellulose; microbicide; prevent; reproductive; safety study; safety testing; tool; vaginal microbicide; volunteer

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 背景： 尽管做出了各种努力来预防和治疗这种疾病，但艾滋病毒仍然是一种日益严重的流行病。 潜在的预防方法包括女性在阴道内使用杀微生物剂、乳膏或凝胶，以保护她们在性交过程中免受感染。 杀菌剂正在开发中，但测试安全性的方法不够灵敏。 在对两种潜在杀菌剂的研究中，科学家们发现使用这些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并未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) 有望作为一种高分辨率、非侵入性方法来评估阴道和子宫颈的内膜（上皮）。 在动物研究中，它可以检测阴道镜检查无法检测到的上皮变化，而阴道镜检查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 将对宫颈阴道上皮产生最小的变化（如果有的话）。 假设 2：OCT 将检测到阴道镜无法检测到的宫颈阴道上皮的微小变化。 具体目标和程序（摘要）： 该研究的主要目的是评估定期使用 N-9 非处方制剂是否会导致 OCT 可检测到但阴道镜无法检测到的上皮毒性。 志愿者将被随机分配在阴道内使用非处方杀精剂 Nonoxynol-9（Conceptrol）或安慰剂凝胶（羟乙基纤维素 - HEC，非处方阴道药物的成分），每天两次，持续 5.5 天。 初次筛查访视后，女性将在访视 1（第 0 天）、访视 2（第 6 天）和访视 3（第 13 天）时通过 OCT 和阴道镜进行评估。 治疗前后，OCT 和阴道镜检查结果将进行比较。 该研究的第二个目的是描述女性参与阴道产品安全研究的动机和障碍，并了解女性对 OCT 和阴道镜检查体验的看法。 这个次要目标是假设生成，因此没有提出计划的假设。 在三个录音半结构化访谈过程中提出的一系列开放式问题将涉及动机、障碍和看法等主题。这些定性数据的分析计划将使每个主题能够识别和总结主题。 实验设计（摘要）： 本研究的招募对象为育龄（18-45 岁）女性。他们将通过 UTMB 每日公告上的传单和研究公告以及口耳相传的方式招募。他们将进行电话筛查，询问有关病史的问题。 符合条件的女性将接受性传播疾病、宫颈发育不良和癌症以及怀孕筛查。 最多将筛选 25 名女性，以招募 18 名女性参与研究；我们预计有些人将因其筛选测试结果而失去资格。 十八名女性将进行初次就诊，并进行 OCT 和阴道镜检查。 然后，参与者将接受安慰剂 (HEC) 或 Nonoxynol-9，每天两次在阴道内使用，持续 5.5 天。 参与者将在最后一次服药当天返回进行重复 OCT 和阴道镜生殖器检查。 在一周未用药后，她将在一周后返回进行 OCT 和阴道镜生殖器检查。 在研究过程中，她将被要求禁欲并且不在阴道内使用其他产品。 每次访问时，她还将接受采访，探讨她参与研究、使用阴道凝胶产品以及接受 OCT 和阴道镜检查的经历。 意义（概要）： 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菌剂后上皮的变化。 如果 OCT 确定能够检测到阴道镜检查中未注意到的变化，正如我们在动物研究中所看到的那样，它具有巨大的潜力，可以增强我们开发安全阴道药物来预防 HIV 的能力，并可能有助于减缓这种疾病的感染率。