An intravaginal ring for real-time evaluation of adherence to topical vagina

用于实时评估局部阴道依从性的阴道环

• 批准号: 8467514
• 负责人: John A Moss
• 金额: $ 21.19万
• 依托单位: AURITEC PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-12 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8467514
• 关键词: AIDS prevention; AIDS/HIV problem; Accounting; Adherence; Animal Model; Behavior; Body Temperature; Cessation of life; Clinic Visits; Clinical Trials; Collection; Computer software; Computers; Data; Development; Devices; Dose; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Effectiveness; Electronics; Evaluation; Failure; Gel; Goals; HIV; Health; Health Personnel; Institutes; Lead; Measurement; Measures; Memory; Methods; Metric; Modeling; Monitor; Mosses; Outcome; Participant; Patient Self-Report; Performance; Personal Computers; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physicians; Placebos; Prevention therapy; Principal Investigator; Process; Randomized; Reporting; Research; Research Personnel; Retrieval; Safety; Schedule; Science; Sheep; Silicones; Simulate; Solutions; Structure; Surface; Tablets; Technology; Telephone; Temperature; Temperature Sense; Tenofovir; Time; Vagina; Vaginal Gel; Vaginal Ring; Woman; Work; base; computerized data processing; cost; design; digital; efficacy evaluation; insight; laptop; microbicide; miniaturize; novel; prevent; product development; programs; public health relevance; sensor; time interval; transmission process; treatment strategy; vaginal fluid; vaginal microbicide

DESCRIPTION (provided by applicant): The broad long-term of this project is to develop methods for evaluation of adherence to intravaginal microbicide therapy for the prevention of HIV transmission. Correct determination of adherence to preventative therapies in clinical trials is essential to accurate evaluation of efficacy. A better understanding of the true adherence to a preventative therapy will lead to the development of products with higher acceptability, and provide insight into the relationship between self-reported use of preventative therapy and actual use. Current methods of adherence evaluation for vaginal microbicide trials include self-reporting by study participants, physician or health care provider assessment, and inspection of study materials (gel applicators or used intravaginal rings) returned during clinic visits. All of these methods are prone to inaccuracy as indicated by the over-reporting of adherence observed in several clinical trials when adherence metrics were compared to trial outcomes. The proposed adherence-monitoring intravaginal ring (adherence IVR) will allow the direct measurement of adherence to IVR-delivered microbicide therapy by monitoring IVR temperature, conductivity, or both continuously on a half-hourly to hourly timescale to determine if the IVR is being worn or not during a clinical trial. The adherence IVR will contain a miniaturized module for sensing temperature (IVR at body temperature when in and below when out) and conductivity (IVR wetted and conductivity high when in, IVR dry and conductivity low when out) to determine adherence state. A microcontroller circuit embedded completely in the silicone ring structure will process the sensor data and store a digital adherence state (1 = IVR in, 0 = IVR out) to non-volatile memory at a fixed time interval. When the ring is removed, typically monthly, the adherence data may be downloaded from the IVR to a laptop computer or other device (smart phone or tablet) to provide a record of adherence that is free from reporting bias. The project has three principal objectives: (1) development of the microcontroller and sensor electronics and embedded software for sensor signal processing, conversion to digital adherence values, and logging to non-volatile memory for subsequent retrieval; (2) incorporation of this adherence monitoring functionality into a pod-IVR for intravaginal delivery of the microbicide tenofovir; and (3) evaluation of adherence monitoring performance, preliminary safety, and pharmacokinetics of tenofovir delivery in a sheep model. At the conclusion of this Phase I effort, a novel method for evaluating adherence to IVR microbicide therapy for prevention of HIV transmission will have been designed, fabricated, and evaluated in an animal model. The adherence-monitoring technology developed here may be extended to other pod-IVR delivery devices (i.e. microbicide combinations) and other IVR platforms.

描述（由申请人提供）：该项目的长期目标是开发评价阴道内杀微生物剂治疗依从性的方法，以预防HIV传播。在临床试验中，正确确定预防性治疗的依从性对于准确评估疗效至关重要。更好地了解预防性治疗的真实依从性将导致开发具有更高可接受性的产品，并深入了解自我报告的预防性治疗使用与实际使用之间的关系。目前阴道杀微生物剂试验的依从性评价方法包括研究参与者的自我报告、医生或医疗保健提供者的评估以及检查临床访视期间返回的研究材料（凝胶涂抹器或使用过的阴道环）。所有这些方法都倾向于不准确，如在将依从性指标与试验结果进行比较时，在几项临床试验中观察到的依从性的过度报告所示。拟定的依从性监测阴道环（依从性IVR）将允许通过在半小时至每小时的时间尺度上连续监测IVR温度、电导率或两者来直接测量对IVR递送的杀微生物剂治疗的依从性，以确定在临床试验期间是否佩戴IVR。依从性IVR将包含一个微型化模块，用于感测温度（IVR在进入时处于体温，在离开时低于体温）和电导率（IVR湿润，在进入时电导率高，IVR干燥，在离开时电导率低），以确定依从性状态。完全嵌入硅胶环结构中的微控制器电路将处理传感器数据，并以固定的时间间隔将数字粘附状态（1 = IVR输入，0 = IVR输出）存储到非易失性存储器中。当环被移除时，通常每月，依从性数据可以从IVR下载到膝上型计算机或其他设备（智能手机或平板电脑），以提供没有报告偏差的依从性记录。该项目有三个主要目标：（1）开发微控制器和传感器电子器件以及用于传感器信号处理的嵌入式软件，转换为数字坚持值，并记录到非易失性存储器以供随后检索;（2）将这种坚持监测功能纳入用于阴道内递送杀微生物剂替诺福韦的pod-IVR;和（3）在绵羊模型中评价替诺福韦递送的依从性监测性能、初步安全性和药代动力学。在第一阶段的努力结束时，一种新的方法来评估遵守IVR杀微生物剂治疗预防艾滋病毒传播将被设计，制造，并在动物模型中进行评估。这里开发的粘附监测技术可以扩展到其他pod-IVR传输设备（即杀微生物剂组合）和其他IVR平台。