The Impact of HIV on Accelerated Aging in the Female Genital Tract: a Pilot Trial of Topical Estradiol to Improve the Vaginal Microbiome and Symptoms of Vaginal Atrophy in Menopausal Women With HIV
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Kerry Murphy
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Most Bothersome Symptom (MBS) of Vaginal Atrophy
研究概览
简要总结
During menopause, there is a decrease in a hormone estrogen, which leads to aging of the vagina. Vaginal aging includes changes in the type and amount of healthy bacteria in the vagina, inflammation and a breakdown of natural barriers that keep the vagina healthy and protected from infections. Some menopausal women develop a condition called vaginal atrophy, which causes vaginal dryness, irritation, pain with sex, and itching. We are testing whether an estradiol tablet placed inside the vagina will lead to fewer changes in the types of bacteria present in the vagina, improve vaginal atrophy symptoms and ultimately keep the vagina healthier for a longer. This is important for women with HIV as they are living longer, healthier, sexually active lives due to successful treatment with antiretrovirals.
详细描述
HIV may be associated with premature aging in the female genital tract including alterations in the vaginal microbiome and mucosal inflammation, which may increase risk for vaginal atrophy, urinary tract infections (UTI) and other genital tract infections. This study will determine whether use of vaginal estradiol for 12 weeks in menopausal women living with HIV with symptomatic vaginal atrophy will improve atrophy symptoms and the vaginal microbiome and reduce mucosal inflammation thereby improving vaginal health. This study will include 50 participants randomized to treatment with a vaginal estradiol insert or no therapy for 12 weeks and will have 4 study visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •HIV infection
- •Females aged 45-70
- •Menopause defined by having no menstrual periods for 12 consecutive months, confirmed with serum follicle-stimulating hormone (FSH) level >40 IU/ml and serum estradiol level <20 pg/ml
- •Symptomatic vaginal atrophy defined as reporting at least once per week in the past 30 days, 1 or more of the following symptoms of moderate or severe intensity: Dryness, Itching, Irritation, Soreness or pain OR Pain associated with sexual activity at least once
- •Evidence of atrophy on exam, including thin, pale and dry vaginal and vulvar surfaces
- •Agrees not to use vaginal products other than vaginal estradiol tablet during the clinical trial
排除标准
- •Current or previous history of breast cancer or estrogen dependent neoplasia
- •Current or past thromboembolic disease (deep vein thrombosis or pulmonary embolism, not including thrombophlebitis)
- •Current or previous history of myocardial infarction or stroke
- •Known blood clotting disorders including Protein C, Protein S and antithrombin deficiency, Factor V Leiden or prothrombin mutations
- •Known severe liver disease including cirrhosis or active Hepatitis B
- •History of adverse reaction to vaginal estradiol
- •Current unexplained or unevaluated abnormal genital bleeding
- •Current or suspected pregnancy
- •If < age 55, had a hysterectomy and has at least one ovary
- •Pelvic or vaginal surgery in the prior 60 days
- •Use of systemic reproductive hormones in the past 2 months
- •Antibiotic use in the past 30 days
- •Use of immunosuppressive medications in the prior 60 days including biologics, chemotherapeutics or post-transplant immunosuppressive medications
- •Use of any vaginal or vulvar preparations 1 month prior to enrollment
- •Current active vaginal infection (diagnosed by wet mount at Visit 1 or 2)
- •Any serious disease or chronic condition that might interfere with study compliance
- •Unwilling to agree to the provisions of the protocol
研究组 & 干预措施
Estradiol Vaginal Insert
Using a pre-loaded single-use plastic applicator, participants will insert one 10 microgram estradiol tablet intravaginally daily for 2 weeks and then one tablet twice weekly for the remainder of the study for a total of 12 weeks.
干预措施: Estradiol Vaginal Insert (Drug)
结局指标
主要结局
Change in Most Bothersome Symptom (MBS) of Vaginal Atrophy
时间窗: Between baseline (Visit 2) and 12 weeks (Visit 5)
Change in the severity of MBS of vaginal atrophy as reported during the baseline visit was assessed at 12 weeks (Visit 5). During the baseline visit, participants were asked to identify their MBS and assess the severity of the MBS on an ordinal scale of "None," "Mild," "Moderate," or "Severe." During the follow-up visit at 12 weeks participants were again asked to identify and assess the severity of their MBS. The degree of severity of the MBS reported at baseline was then compared to the severity of the MBS reported at 12 weeks and categorically summarized and reported as either "Severity Increased" "Severity Decreased" or "No change in Severity" for the given MBS. Participants whose MBS reported at baseline changed during the follow-up visit at 12 weeks were excluded from the analysis. Participants who did not report an MBS during the baseline visit were also excluded. Data for each possible type of MBS is summarized by study arm.
Vaginal Microbiome - Relative Abundance of Lactobacillus Crispatus (L. Crispatus)
时间窗: Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
The relative abundance of the protective Lactobacillus species, L. crispatus, as quantified by lllumina MiSeq sequencing will be calculated by dividing the total number of L crispatus sequences detected in a sample by the total number of sequences from all bacterial species detected in the same sample. This proportion will be expressed as a percentage. The change in relative abundance between baseline (visit 2) and 12 weeks (visit 5) will be summarized by study arm.
Vaginal Microbiome - Quantitative Determination of Protective Lactobacilli Species
时间窗: Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Changes in the vaginal microbiome, specifically the quantities of protective Lactobacilli species (L. crispatus, L. jensenii and L. gasseri) as measured by quantitative PCR (qPCR) will be determined. The three Lactobacilli species will be identified and quantified in colony forming units per milliliter of sample (CFU/mL). Changes in abundance from baseline will be summarized by study arm using basic descriptive statistics.
次要结局
- Vaginal Microbiome - Relative Abundance of Bacterial Vaginosis Associated Species(Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5))
- Vaginal Microbiome - Quantitative Determination of Bacterial Vaginosis Associated Species(Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5))
- Change in Vaginal Cytokine and Chemokine Concentrations(Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5))
研究者
Kerry Murphy
Assistant Professor, Department of Medicine (Infectious Diseases)
Albert Einstein College of Medicine