Multicenter Interventional Lymphangioleiomyomatosis Early Disease Trial (MILED) - DCC
多中心介入性淋巴管平滑肌瘤病早期疾病试验 (MILED) - DCC
基本信息
- 批准号:10249943
- 负责人:
- 金额:$ 29.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-20 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdverse eventAromatase InhibitorsBenignBiological MarkersCellsCessation of lifeChargeChronicChronic Myeloid LeukemiaClinicClinicalCommunitiesCystDataData Coordinating CenterDepartment of DefenseDevelopmentDiffuseDiseaseDisease ProgressionDoseEligibility DeterminationEnrollmentFDA approvedFRAP1 geneFloridaFoundationsFrightGasesGenesGleevecGoalsGrowthGrowth FactorImpairmentInformation DisseminationInfrastructureInternationalInterventionInvestmentsJapanKnowledgeLeadLungLung diseasesLymphangiogenesisLymphangioleiomyomatosisMagnetic Resonance ImagingMeasuresMolecularMutationNeoplasm MetastasisNeoplasmsPathogenesisPathway interactionsPatient ParticipationPatientsPerformancePharmaceutical PreparationsPhasePlacebosPleural effusion disorderPneumothoraxPrognostic MarkerPulmonary Function Test/Forced Expiratory Volume 1Pulmonary function testsQuality of lifeRandomizedRecurrenceRespiratory FailureSafetySerumSeveritiesSignal TransductionSirolimusSiteSmooth MuscleSmooth Muscle MyocytesSourceTimeToxic effectTuberous SclerosisUniversitiesVascular Endothelial Growth Factor DVital capacityWomanadvanced diseaseairway obstructionbiomarker discoverydata managementdiagnostic biomarkerdisabilityimprovedlung injurylung preservationlung volumemTOR InhibitormTOR inhibitionmiddle agemortalityneoplasticplacebo grouppreventprimary endpointprogramspulmonary functionpulmonary function declinerandomized placebo controlled trialrate of changerecruitrespiratorysecondary endpointside effecttargeted treatment
项目摘要
Project summary/abstract
Lymphangioleiomyomatosis (LAM) is low-grade metastasizing neoplasm of women, driven by activating
mutations in the mTOR pathway that result in cystic destruction of the lung. The benign appearing, mutation
bearing smooth muscle-like LAM cells that infiltrate the lung arise from an unknown source and execute a
program of matrix remodeling that leads to cyst formation, recurrent pneumothorax, chylous pleural effusion
and progressive respiratory failure. There has been tremendous progress in LAM in the past decade, including
a rich molecular understanding of disease pathogenesis, development of a diagnostic and prognostic
biomarker, and the discovery of a treatment. The randomized controlled Rare Lung Disease Consortium
(RLDC) Multicenter International LAM Efficacy of Sirolimus (MILES) Trial (Sponsor-FXM, IND 71,340)
demonstrated that mTOR inhibition with sirolimus is an effective suppressive therapy for LAM, stabilizing lung
function, functional performance, and quality of life in women with abnormal lung function. Side effects due to
sirolimus were common in MILES, although SAEs were balanced in the sirolimus and placebo groups. The
beneficial effects of sirolimus waned when the drug was held in the second year of the trial. Although the
primary eligibility criterion was forced expiratory volume in 1 second (FEV1) ≤ 70%, enrolled MILES patients
had more advanced respiratory impairment, with about half of lung function remaining (on average), limiting the
generalizability of the findings to mild disease. Fear of toxicities and lifelong therapy lead most clinicians and
patients to wait until lung function becomes abnormal before initiating sirolimus therapy to stabilize the
damaged lung. This approach is suboptimal and inadequate. The Multicenter Interventional LAM Early Disease
Trial (MILED) is phase III, randomized, placebo-controlled trial to determine if early, long term (2 yr), low dose
(1 mg/day) sirolimus treatment of patients with well-preserved lung function will safely prevent disease
progression. Sixty patients with normal FEV1 (FEV1>70%) will be enrolled and randomized to 1 mg/day
sirolimus or placebo, and followed for 2 years with pulmonary function testing every 4 months. The primary
endpoint will be the between-group (placebo vs. sirolimus) difference in the rate of change in FEV1 (in liters).
Secondary endpoints will include between group differences in adverse events, forced vital capacity, lung
volumes, diffusing capacity, serum VEGF-D, and early airflow obstruction assessed using hyper-polarized gas
MRI. The study will be conducted using the infrastructure created for the RLDC, using the Rare Lung Disease
Clinic Network, which is currently following over 1300 U.S. LAM patients and conducting the TRAIL trial. The
LAM Foundation will be an integral partner and will assist with study recruitment and patient participation. Data
will be managed by the University of South Florida Data Management and Coordinating Center. Successful
completion of these aims will define the safety and efficacy of low dose sirolimus in patients with normal lung
function, and determine if sirolimus can be used to prevent disease progression to symptomatic stages.
项目总结/文摘
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)
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JEFFREY P KRISCHER其他文献
JEFFREY P KRISCHER的其他文献
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{{ truncateString('JEFFREY P KRISCHER', 18)}}的其他基金
Limited Competition: Continued Follow-up of Subjects and Initiation of a Second Case-control Cohort in The Environmental Determinants of Diabetes in The Young Study (TEDDY)
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- 批准号:
10398923 - 财政年份:2021
- 资助金额:
$ 29.14万 - 项目类别:
Human gene transfer & macrophage cell transplantation therapy of hereditary PAP (hPAP)
人类基因转移
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10403442 - 财政年份:2021
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Human gene transfer & macrophage cell transplantation therapy of hereditary PAP (hPAP)
人类基因转移
- 批准号:
10179934 - 财政年份:2021
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$ 29.14万 - 项目类别:
Limited Competition: Continued Follow-up of Subjects and Initiation of a Second Case-control Cohort in The Environmental Determinants of Diabetes in The Young Study (TEDDY)
有限的竞争:在年轻研究中糖尿病的环境决定因素(TEDDY)中继续对受试者进行随访并启动第二个病例对照队列
- 批准号:
10227415 - 财政年份:2021
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$ 29.14万 - 项目类别:
Human gene transfer & macrophage cell transplantation therapy of hereditary PAP (hPAP)
人类基因转移
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10702185 - 财政年份:2021
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$ 29.14万 - 项目类别:
Follow-up on Subjects, Integrative Data Analysis and Measurement of Viral Antibodies in The Environmental Determinants of Diabetes in The Young Study (TEDDY)
青年糖尿病环境决定因素研究(TEDDY)中的受试者跟踪、综合数据分析和病毒抗体测量
- 批准号:
10392400 - 财政年份:2020
- 资助金额:
$ 29.14万 - 项目类别:
Follow-up on Subjects, Integrative Data Analysis and Measurement of Viral Antibodies in The Environmental Determinants of Diabetes in The Young Study (TEDDY)
青年糖尿病环境决定因素研究(TEDDY)中的受试者跟踪、综合数据分析和病毒抗体测量
- 批准号:
10260891 - 财政年份:2020
- 资助金额:
$ 29.14万 - 项目类别:
NIDDK Follow-up on Subjects and Immunological Assessments in The Environmental Determinants of Diabetes In The Young Study (TEDDY) (UC4)
NIDDK 青年糖尿病环境决定因素研究 (TEDDY) (UC4) 中受试者和免疫学评估的后续行动
- 批准号:
10088137 - 财政年份:2017
- 资助金额:
$ 29.14万 - 项目类别:
Data Coordinating Center for Type 1 Diabetes TrialNet (UC4)USF: TrialNet UC4-3
1 型糖尿病数据协调中心 TrialNet (UC4)USF:TrialNet UC4-3
- 批准号:
9506924 - 财政年份:2017
- 资助金额:
$ 29.14万 - 项目类别:
Multicenter Interventional Lymphangioleiomyomatosis Early Disease Trial (MILED) - DCC
多中心介入性淋巴管平滑肌瘤病早期疾病试验 (MILED) - DCC
- 批准号:
9743827 - 财政年份:2016
- 资助金额:
$ 29.14万 - 项目类别:
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