Hormone Therapy for Peri- and Postmenopausal Women with HIV (HoT)
Hormone Therapy for Peri- and Postmenopausal Women with HIV (HoT)
批准号:
10698682
负责人:
Sara Hurtado Bares
金额:
$79.79万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-01 至 2028-08-31
关键词:
AIDS clinical trial groupAccelerationAffectAgingAnti-Inflammatory AgentsBiological AssayBiological MarkersBiometryCardiovascular DiseasesCaringCell CommunicationChronicCross-Over TrialsDataDetectionDevelopmentDouble-Blind MethodDown-RegulationEligibility DeterminationEndocrinologyEstrogen TherapyEstrogensExperimental ModelsFractureFutureGenetic TranscriptionGoalsGynecologyHIVHIV-1HealthHeart DiseasesHormonal ChangeHot flushesImmunologyImpaired cognitionInflammationInfrastructureLife ExpectancyMeasuresMediatingMedicineMenopausal SymptomMenopausal SyndromeMenopauseMental HealthMoodsNeurocognitionNeurocognitiveNeurocognitive DeficitNight SweatingOralOsteoporosisOutcomePathway interactionsPerimenopausePersonsPlacebo ControlPlacebosPostmenopausePreventionProcessProgesteronePropertyPsychologyQuality of lifeRNARandomizedResearchResearch PersonnelResidual stateResourcesRiskRoleSleepSymptomsVirusVisitWomanWomen&aposs Healthantiretroviral therapybonebone lossbone turnovercancer riskcardiometabolismcardiovascular risk factorcomorbiditydesigneffective therapyefficacy evaluationendothelial dysfunctionexperiencehigh riskhormone therapyimmune activationimprovedinnovationinterestmenopausal hormone therapymonocytemultidisciplinaryneurocognitive disorderolder womenpreventprospectivereproductive senescencesymptom treatmentsystemic inflammatory responsetherapy adherencetransdermal estrogentreatment responsevasomotor symptomsvirology
中文摘要
随着有效的联合抗逆转录病毒疗法(ART)的预期寿命延长,更多携带艾滋病毒的妇女
(WWH)正进入更年期。WWH经历更频繁和更严重的血管运动症状(VMS;
潮热和盗汗的统称)比没有感染艾滋病毒的妇女要多。更年期的转变是
还与骨质疏松/骨折等与衰老相关的合并症风险增加有关,
心血管疾病和神经认知障碍对WWH的影响不成比例。更年期
激素疗法(HT)是VMS最有效的治疗方法,但利用率低,且从未
在WWH上进行了研究。我们提出了一项随机、双盲、安慰剂对照、2x2交叉试验(n=80)。
评价经皮雌激素联合口服黄体酮与安慰剂治疗对症的疗效
围绝经期和绝经早期合并VMS的WWH(目标1)。我们还将比较高温与高温的效果。
安慰剂对神经认知功能、情绪、睡眠和生活质量的影响
已在更年期期间的WWH中进行了专门研究(目标2)。羟色胺具有显著的抗炎作用;
因此,我们将评估羟色胺对骨和心脏代谢健康生物标记物的影响,并检测
全身炎症的作用(目标3)。最后,我们将使用
通过基于诱导转录的测序(EDITS)分析检测包膜,提供前瞻性
用实验数据验证WWH后可诱导的HIV宿主增加的观测数据结果
更年期(探索性目标)。我们的建议利用了艾滋病诊所的资源和基础设施
试验组(ACTG)。资格标准和终端也设计为与MsFLASH保持一致
(更年期策略:寻找持久的症状答案和健康试验)网络试验允许
未来的分析比较了携带和不携带HIV的妇女的羟色胺反应。我们的研究结果将提供
关于羟色胺在预防衰老相关并发症中的作用的关键信息,并将阐明
全身性炎症是一种可改变的机制途径。此外,这次试验将为今后的工作奠定基础。
高血压与非激素治疗VMS及预防合并症的研究
老化的WWH。
英文摘要
As life expectancy increases with effective combination antiretroviral therapy (ART), more women with HIV
(WWH) are reaching menopause. WWH experience more frequent and severe vasomotor symptoms (VMS;
the collective term for hot flashes and night sweats) than women without HIV. The menopausal transition is
also associated with increasing risk of aging-related comorbidities such as osteoporosis/fracture,
cardiovascular disease and neurocognitive impairment that disproportionately affect WWH. Menopausal
hormone therapy (HT) is the most effective treatment for VMS; however, utilization is low and HT has never
been studied in WWH. We propose a randomized, double-blind, placebo-controlled, 2x2 cross-over trial (n=80)
to evaluate the efficacy of HT (transdermal estrogen plus oral progesterone) versus placebo for symptomatic
peri- and early post-menopausal WWH with VMS (Aim 1). We will also compare the effects of HT versus
placebo on neurocognitive function, mood, sleep and quality of life using a battery of assessments that have
been studied specifically in WWH during menopause (Aim 2). HT has noted anti-inflammatory properties;
therefore, we will evaluate the effect of HT on biomarkers of bone and cardiometabolic heath and examine the
role of systemic inflammation (Aim 3). Lastly, we will measure effects of HT on the HIV reservoir using the
Envelope Detection by Induced Transcription-based Sequencing (EDITS) assay, providing prospective
experimental data to validate observational data findings of increased inducible HIV reservoir in WWH after
menopause (Exploratory Aim). Our proposal leverages the resources and infrastructure of the AIDS Clinical
Trials Group (ACTG). Eligibility criteria and endpoints have also been designed to align with MsFLASH
(Menopause Strategies: Finding Lasting Answers for Symptoms and Health Trials) network trials to allow for
future analyses comparing HT response in women with and without HIV. The results of our study will provide
critical information about the role of HT in prevention of aging-related comorbidities and will elucidate whether
systemic inflammation is a modifiable mechanistic pathway. Further, this trial will set the groundwork for future
research comparing HT to non-hormonal therapies for treatment of VMS and prevention of comorbidities in
aging WWH.
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