Letrozole for Treatment of Uterine Fibroids: A randomized, placebo-controlled trial
来曲唑治疗子宫肌瘤:一项随机、安慰剂对照试验
基本信息
- 批准号:10718036
- 负责人:
- 金额:$ 69.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AccountingAdverse effectsAdverse eventAgeAromataseAromatase InhibitorsBackBiologicalBlindedCaringCellsClinicalClinical DataClinical ResearchClinical TrialsControl GroupsDataDevelopmentDiseaseDoseDrug usageEconomicsEnrollmentEnzymesEstrogensFDA approvedFibroid TumorFollow-Up StudiesFunctional disorderGoalsGonadotropin Hormone Releasing HormoneGonadotropinsGrowthHemorrhageHormonalHormone AntagonistsHormone useHormonesHot flushesHypertensionHysterectomyInfertilityIntestinesLetrozoleLong-Term EffectsMediatingMedicalMenopauseOperative Surgical ProceduresOralOutcomeOvarianOvarian hormoneOvaryParticipantPatientsPelvic PainPelvisPharmaceutical PreparationsPhasePlacebosPopulationPopulation HeterogeneityPostoperative PeriodPremenopauseProceduresProductionProgestinsQuality of lifeQuestionnairesRandomizedRecoveryReportingRiskSafetySerumSmooth Muscle TumorSourceSymptomsTestingTimeUncontrolled StudyUterine FibroidsUterine myomectomyUterusWomanWorkadverse pregnancy outcomeautocrineblack womencare costsclinical outcome assessmentdisabilityefficacy evaluationethnic diversityfollow-uphormone therapyimprovednovelnovel therapeuticsopen labelparacrineplacebo controlled trialpreferencepressureracial diversityrandomized placebo controlled trialreduce symptomssafety assessmentside effectsocialsymptomatic improvementtumorultrasoundurinary
项目摘要
PROJECT SUMMARY
Uterine fibroids are smooth muscle tumors that occur in >80% of Black women and 70% of white
women by age 50 years. Fibroids cause heavy menstrual bleeding, pelvic pain or pressure, urinary and bowel
dysfunction, infertility, and adverse pregnancy outcomes. Major surgery with hysterectomy and myomectomy is
the most common fibroid treatment, but surgery generally requires 2-6 weeks of recovery with substantial time
off work and the inability to perform usual activities. To avoid surgery, many women prefer medical therapy for
fibroids, but few options are available. There are only two FDA approved oral medications to treat fibroids,
GnRH antagonists that block gonadotropins and diminish ovarian estrogen production akin to menopause.
These medications require concomitant use of estrogen and progestin “add-back” therapy to mitigate hot
flashes and other side effects and risks of low serum estrogen. Many women aim to avoid this long-term
hormone therapy or have contraindications to hormone use. New medications that alleviate fibroid
symptoms but avoid low serum estrogen are needed to improve care for women with fibroids.
Fibroids are hormonally responsive tumors that decrease in volume when deprived of estrogen. The
ovary is the primary source of estrogen in premenopausal women, but fibroid cells also produce local estrogen
through activity of the aromatase enzyme. Through both autocrine and paracrine action, estrogen produced by
fibroids demonstrates local control over fibroid growth. Letrozole is an aromatase inhibitor (AI) that blocks
estrogen synthesis within fibroid cells. Therefore, letrozole may decrease fibroid volume and improve
symptoms. Low doses of letrozole will inhibit the modest aromatase activity within fibroids, but not significantly
block the robust aromatase activity in the ovaries of premenopausal women. Letrozole may serve as a novel
therapy that improves fibroid symptoms without adverse effects of low serum estrogen.
Despite a biologic mechanism to support AIs as a fibroid treatment, clinical data is very limited. In a few
small uncontrolled studies, fibroid volume decreased 35-55% during 8-12 weeks of treatment. We recently
completed a pilot, randomized, placebo-controlled trial of letrozole. The letrozole group had greater
improvement in fibroid symptoms and quality of life compared with the placebo during 2 months of treatment
and reported few side effects. Building on this preliminary data, we propose a full scale randomized, blinded,
placebo-controlled trial that is powered to detect clinically meaningful changes in fibroid symptoms and fibroid
volume. We will enroll 140 racially and ethnically diverse premenopausal women randomly assigned to oral
letrozole 2.5mg/day or an identical placebo for 3 months and assess clinical outcomes and the development of
adverse events. We will also evaluate long-term letrozole use with an open-label follow-up phase for up to 6
months of letrozole therapy. This trial will provide gold standard evidence to evaluate the efficacy of a
novel treatment for uterine fibroids that has significant advantages over existing medication.
项目概要
子宫肌瘤是平滑肌肿瘤,发生于 >80% 的黑人女性和 70% 的白人女性
50 岁以上的女性,子宫肌瘤会导致月经大量出血、盆腔疼痛或压迫感、泌尿和肠道不适。
功能障碍、不孕和不良妊娠结局是子宫切除术和子宫肌瘤切除术的主要手术。
最常见的肌瘤治疗方法,但手术一般需要 2-6 周的恢复时间,需要相当长的时间
下班和无法进行日常活动 为了避免手术,许多女性更喜欢药物治疗。
肌瘤,但只有两种 FDA 批准的口服药物可以治疗肌瘤。
GnRH 拮抗剂可阻断促性腺激素并减少卵巢雌激素的产生,类似于更年期。
这些药物需要同时使用雌激素和孕激素“回加”疗法来缓解热
许多女性希望长期避免这种情况的出现和其他副作用以及低血清雌激素的风险。
激素治疗或有激素使用禁忌症的新药物可以缓解子宫肌瘤。
需要改善对患有肌瘤的女性的护理,但需要避免低血清雌激素。
肌瘤是一种激素反应性肿瘤,当缺乏雌激素时,其体积会缩小。
卵巢是绝经前女性雌激素的主要来源,但肌瘤细胞也会产生局部雌激素
通过芳香酶的活性,通过自分泌和旁分泌作用,产生雌激素。
肌瘤显示出对肌瘤生长的局部控制。来曲唑是一种芳香酶抑制剂 (AI),可以阻止肌瘤生长。
因此,来曲唑可以减少子宫肌瘤体积并改善子宫肌瘤。
低剂量的来曲唑会抑制肌瘤内适度的芳香酶活性,但效果并不显着。
阻断绝经前女性卵巢中强大的芳香酶活性,来曲唑可能是一种新药。
改善子宫肌瘤症状且无低血清雌激素副作用的疗法。
尽管有生物机制支持人工智能作为子宫肌瘤的治疗方法,但临床数据非常有限。
我们最近进行了小型非对照研究,在 8-12 周的治疗期间,肌瘤体积减少了 35-55%。
完成了一项来曲唑试验、随机、安慰剂对照试验,来曲唑组的疗效更好。
治疗 2 个月期间,与安慰剂相比,肌瘤症状和生活质量得到改善
并报告了一些副作用,基于这些初步数据,我们提出了全面的随机、盲法。
安慰剂对照试验,旨在检测肌瘤症状和肌瘤的临床有意义的变化
我们将招募 140 名不同种族和民族的绝经前女性,随机分配到口腔组。
来曲唑 2.5 毫克/天或相同的安慰剂,持续 3 个月,并评估临床结果和发展
我们还将评估来曲唑的长期使用,并进行长达 6 年的开放标签随访阶段。
该试验将为评估来曲唑治疗的疗效提供金标准证据。
子宫肌瘤的新型治疗方法,与现有药物相比具有显着优势。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Alison Huang其他文献
Alison Huang的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Alison Huang', 18)}}的其他基金
Promoting Clinical and Translational Science Training and Career Development for Residents
促进住院医师的临床和转化科学培训和职业发展
- 批准号:
10598346 - 财政年份:2023
- 资助金额:
$ 69.49万 - 项目类别:
Language-Concordant Mobile Health Training and Support for Behavioral Management of Urinary Incontinence for Women with Limited English Proficiency
为英语水平有限的女性提供语言一致的移动健康培训和尿失禁行为管理支持
- 批准号:
10772574 - 财政年份:2022
- 资助金额:
$ 69.49万 - 项目类别:
Cognitive, urinary, and functional trajectories of older women using pharmacologic treatment strategies for urgency incontinence
使用药物治疗策略治疗急迫性尿失禁的老年女性的认知、泌尿和功能轨迹
- 批准号:
10563201 - 财政年份:2022
- 资助金额:
$ 69.49万 - 项目类别:
Cognitive, urinary, and functional trajectories of older women using pharmacologic treatment strategies for urgency incontinence
使用药物治疗策略治疗急迫性尿失禁的老年女性的认知、泌尿和功能轨迹
- 批准号:
10343015 - 财政年份:2022
- 资助金额:
$ 69.49万 - 项目类别:
Cognitive, urinary, and functional trajectories of older women using pharmacologic treatment strategies for urgency incontinence Administrative supplement
使用药物治疗策略治疗急迫性尿失禁的老年女性的认知、泌尿和功能轨迹行政补充
- 批准号:
10635598 - 财政年份:2022
- 资助金额:
$ 69.49万 - 项目类别:
Cognitive, urinary, and functional trajectories of older women using pharmacologic treatment strategies for urgency incontinence Administrative supplement
使用药物治疗策略治疗急迫性尿失禁的老年女性的认知、泌尿和功能轨迹行政补充
- 批准号:
10635598 - 财政年份:2022
- 资助金额:
$ 69.49万 - 项目类别:
Promoting Multidisciplinary Clinical and Translational Science in Aging by Resident Investigators
常驻研究人员促进老龄化领域的多学科临床和转化科学
- 批准号:
10333347 - 财政年份:2021
- 资助金额:
$ 69.49万 - 项目类别:
Promoting Multidisciplinary Clinical and Translational Science in Aging by Resident Investigators
常驻研究人员促进老龄化领域的多学科临床和转化科学
- 批准号:
10557121 - 财政年份:2021
- 资助金额:
$ 69.49万 - 项目类别:
A Feasibility Trial of a Group Based Yoga Intervention for Chronic Pelvic Pain in Women
基于团体的瑜伽干预治疗女性慢性盆腔疼痛的可行性试验
- 批准号:
9976159 - 财政年份:2020
- 资助金额:
$ 69.49万 - 项目类别:
相似国自然基金
基于真实世界医疗大数据的中西药联用严重不良反应监测与评价关键方法研究
- 批准号:82274368
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
OR10G7错义突变激活NLRP3炎症小体致伊马替尼严重皮肤不良反应的机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
基于隐狄利克雷分配模型的心血管系统药物不良反应主动监测研究
- 批准号:82273739
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
基于真实世界数据的创新药品上市后严重罕见不良反应评价关键方法研究
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
D.formicigenerans菌通过调控FoxP3-Treg影响PD-1抑制剂所致免疫相关不良反应的机制研究
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Heat-Related Health Risk Assessment and Mitigation for Aging Populations in Public Housing: A Community-Individual Environment-Health Nexus
公共住房中与热相关的健康风险评估和老龄化人口缓解:社区-个人环境-健康关系
- 批准号:
10587936 - 财政年份:2023
- 资助金额:
$ 69.49万 - 项目类别:
Pandemic-Related Disruptions in care for Veterans on Insulin Pumps (PD-VIP): A Mixed Methods Analysis
与流行病相关的胰岛素泵退伍军人护理中断 (PD-VIP):混合方法分析
- 批准号:
10637010 - 财政年份:2023
- 资助金额:
$ 69.49万 - 项目类别:
Physical Frailty and Symptom Monitoring and Management Behaviors in Heart Failure (PRISM-HF)
心力衰竭的身体虚弱和症状监测和管理行为 (PRISM-HF)
- 批准号:
10740609 - 财政年份:2023
- 资助金额:
$ 69.49万 - 项目类别:
Risk factors for chronic obstructive pulmonary disease exacerbations, quality of care, and outcomes in people with HIV
HIV 感染者慢性阻塞性肺病恶化的危险因素、护理质量和结果
- 批准号:
10700228 - 财政年份:2023
- 资助金额:
$ 69.49万 - 项目类别:
Sensor Hardware and Intelligent Tools for Assessing the Health Effects of Heat Exposure
用于评估热暴露对健康影响的传感器硬件和智能工具
- 批准号:
10522560 - 财政年份:2022
- 资助金额:
$ 69.49万 - 项目类别: