Effect of Tenofovir on Genital HSV Shedding: a Randomized, Double-blind, Placebo-controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo
研究概览
简要总结
The investigators propose a randomized, double blind, placebo-controlled, cross-over trial to evaluate the effect of oral and topical (vaginal gel) tenofovir on genital herpes simplex virus (HSV) shedding among herpes simplex virus type-2 (HSV-2) seropositive, human immunodeficiency virus (HIV) seronegative women. The investigators hypothesize that tenofovir will reduce genital HSV shedding compared to placebo.
详细描述
The investigators propose a randomized, double-blind, placebo-controlled, cross-over study of 55 adult, healthy women who are HSV-2 seropositive and HIV-1 seronegative. Women will first participate in a run-in phase with twice daily swabbing. Following 4 weeks of swabbing, participants will be randomized 2:2:1 to one of three groups: 1) oral tenofovir and placebo gel, 2) oral placebo and tenofovir gel, or 3) oral placebo and placebo gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drug will be administered daily.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women age 18-50
- •HSV-2 seropositive by the University of Washington (UW) Western blot
- •History of recurrent genital herpes, with more than 4 recurrences but less than 10 in the last year or, if currently on suppressive therapy, with more than 4 recurrences but less than 10 in the year prior to starting suppressive therapy
- •HIV negative
- •General good health
- •Willing to not use antiviral therapy (other than the study drug) for the duration of the study
- •Willing to obtain a swab from genital secretions twice daily for the duration of the study
- •Willing to use effective birth control
- •Able to provide written informed consent at screening and enrollment
排除标准
- •HIV positive or at high risk for HIV acquisition (intravenous drug user or HIV+ sex partner)
- •Hepatitis B (HepB) antigen (Ag) positive, or at high risk for HepB acquisition and not vaccinated
- •Have a history of adverse reaction to tenofovir and/or adefovir
- •Immunosuppressive medications, except for intranasal or topical (not high potency) steroids.
- •Any kidney disease, or renal insufficiency, defined as serum creatinine >1.5 mg/dl. Participants with a prior history of a single episode of pyelonephritis will be eligible.
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times upper limit of normal
- •Pregnancy, as confirmed by a urine pregnancy test, planning to become pregnant during the course of the trial, or breast-feeding.
- •Serious medical conditions or active infections
- •Any other conditions that in the judgment of the investigator would preclude successful completion of the clinical trial.
研究组 & 干预措施
Study Drug Phase: TDF
Participants will take tenofovir disoproxil fumarate (TDF) tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
干预措施: TDF (Drug)
Study Drug Phase: TDF
Participants will take tenofovir disoproxil fumarate (TDF) tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
干预措施: Placebo Vaginal Gel (Drug)
Study Drug Phase: Vaginal TFV Gel
Participants will take oral placebo tablets and apply a tenofovir 1% (TFV) vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
干预措施: Vaginal TFV Gel (Drug)
Study Drug Phase: Vaginal TFV Gel
Participants will take oral placebo tablets and apply a tenofovir 1% (TFV) vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
干预措施: Placebo Tablets (Drug)
Study Drug Phase: Double Placebo
Participants will take oral placebo tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
干预措施: Placebo Vaginal Gel (Drug)
Study Drug Phase: Double Placebo
Participants will take oral placebo tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
干预措施: Placebo Tablets (Drug)
结局指标
主要结局
HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo
时间窗: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase
The within-person changes in rate of HSV shedding during study drug administration (treatment phase) compared with the rate of HSV shedding during lead-in observation phase in the same participants. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment. This is analyzed separately for each treatment arm and not compared between arms.
次要结局
- Within-person Changes in Log-copy Numbers of HSV(Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase)
- Asymptomatic Shedding (Shedding on Days Without Genital Lesions)(Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase)
- Genital Lesion Rate(Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase)
研究者
Anna Wald
Professor
University of Washington