The COURAGE Trial: Colon Recurrence and Aerobic Exercise: A Feasibility Study

COURAGE 试验：结肠复发和有氧运动：可行性研究

• 批准号: 8867184
• 负责人: Kathryn H. Schmitz
• 金额: $ 20.92万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-10 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8867184
• 关键词: Achievement; Address; Adjuvant Chemotherapy; Aerobic Exercise; Behavior Therapy; Biological; Biological Markers; Blood; Blood Vessels; Cancer Prognosis; Cancer Survivor; Cancer Survivorship; Carcinoembryonic Antigen; Cell Adhesion; Cell Adhesion Molecules; Clinical; Colon; Colon Carcinoma; Control Groups; Development; Diagnosis; Disease; Disease-Free Survival; Distant; Distant Metastasis; Dose; Epidemiology; Event; Excision; Exercise; Extracellular Matrix; Extravasation; Feasibility Studies; Frequencies; Goals; Growth; Guidelines; Health; Healthcare; Heart failure; Home environment; Incidence; Infiltration; Intercellular adhesion molecule 1; Intervention; Investigation; Knowledge; Life Style; Longevity; Malignant Neoplasms; Medical; Metabolic syndrome; Metastatic/Recurrent; Mission; Molecular; Monitor; National Cancer Institute; Neoplasm Circulating Cells; Neoplasm Metastasis; Obesity; Operative Surgical Procedures; Organ; Outcome; Participant; Pathway interactions; Patients; Peripheral arterial disease; Physical activity; Pilot Projects; Play; Prognostic Marker; Progressive Disease; Randomized; Recurrence; Recurrent disease; Regional Disease; Research; Resources; Risk; Role; Safety; Serum; Severities; Site; Stream; Survival Rate; Survivors; Symptoms; Training; Tumor Cell Invasion; United States; Waiting Lists; adverse outcome; base; cancer diagnosis; cancer recurrence; chemotherapy; epidemiologic data; exercise adherence; experience; improved; lifestyle intervention; lymph nodes; mortality; phase III trial; response; success; tumor growth; tumor progression

DESCRIPTION (provided by applicant): The high rate of recurrent disease is a critical barrier to promote the health and longevity of colon cancer (CC) survivors. An approach to reduce this barrier is to develop interventions to minimize recurrence that CC survivors can accomplish autonomously, such as lifestyle and behavioral modification. Epidemiologic evidence suggests that increasing levels of post-diagnosis physical activity is associated with a 42% improvement in disease-free survival, 40% reduction in recurrence, and 45-71% reduction in CC-specific mortality. However, the underlying molecular mechanisms of this association remain unidentified. Characterizing biomarkers that promote existing tumor growth and dissemination of circulating tumor cells (CTCs) may advance knowledge of CC recurrence and progression. Cell-adhesion molecules play a pivotal role in the development and progression of CC recurrence. Cell-adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular adhesion molecule-1 (sVCAM-1), promote the growth and progression of existing micro-metastases, and promote the formation of additional metastatic foci by enabling CTC invasion of the extracellular matrix, infiltration and dissemination throughout the blood stream, and extravasation into distant organs. This pilot study will randomize 39 CC survivors to three equal-sized groups: low dose (150 min�wk-1) moderate-intensity aerobic exercise, high-dose (300 min�wk-1) moderate-intensity aerobic exercise, or a control group, for 26-weeks. Participants will be provided with in-home treadmills to support the achievement of these exercise goals. Our research team has demonstrated success in prescribing these volumes of aerobic exercise. The primary aims of this trial are to quantify and describe the feasibility, incidence of healthcare events requiring dose-reduction or cessation of exercise and to gather preliminary evidence regarding the biologic efficacy of two distinct doses of aerobic exercise on two cell-adhesion biomarkers associated with CC recurrence and metastasis (sICAM-1 and sVCAM-1). We will then explore the relationship between cell-adhesion molecules and CTCs. This line of investigation aligns with the current mission of the National Cancer Institute PAR-12-229, and provocative question PQA-5, which aim to elucidate the optimal exercise prescription to improve molecular pathways hypothesized to underlie the association between physical activity and cancer prognosis.

描述（由适用提供）：较高的复发疾病率是促进结肠癌（CC）生存的健康和寿命的关键障碍。减少这种障碍的一种方法是制定干预措施，以最大程度地减少CC生存可以自主完成的复发，例如生活方式和行为改变。流行病学证据表明，诊断后体育活动的水平升高与无疾病生存率提高42％，复发率降低了40％，CC特异性死亡率降低了45-71％。但是，该关联的潜在分子机制仍然不明。表征促进现有肿瘤生长并传播循环肿瘤细胞（CTC）的生物标志物可能会提高对CC复发和进展的了解。细胞粘附分子在CC复发的发展和发展中起关键作用。细胞粘附分子，例如固体间间粘附分子-1（SICAM-1）和固体血管粘附分子-1（SVCAM-1），促进现有微构酶的生长和进展，并通过促进其他转移性灶的形成，从而促进其他转移性局部范围内的转移量表，并促进循环范围内的胞外基质和脉冲式脉冲，并促进了脉络序列式及其流质的脉络脉冲，并促进了脉络及其量表的脉络量表。拆卸器官。这项试点研究将将39个CC存活随机至三个等尺寸的组：低剂量（150分钟）中等强度有氧运动，高剂量（300 min.wk-1）中等强度有氧运动或一个对照组，用于26惠克。将为参与者提供家庭跑步机，以支持这些运动目标的实现。我们的研究团队在开处方这些有氧运动方面取得了成功。该试验的主要目的是量化和描述需要减少剂量或停止运动的医疗保健事件的发生率，并收集有关两种与CC复发和转移（SICAMASIS和SICAMASIS（SICAM-1和SVCAM）相关的两种不同剂量有氧运动生物标志物的生物学效率的初步证据。然后，我们将探索细胞粘附分子与CTC之间的关系。这一投资线与国家癌症研究所Par-12-229的当前使命以及挑衅性问题PQA-5保持一致，该问题旨在阐明最佳的运动处方，以改善假设体育活动与癌症预后之间关联的分子途径。

项目成果

Anthropometrically-predicted visceral adipose tissue and mortality among men and women in the third national health and nutrition examination survey (NHANES III).

• DOI: 10.1002/ajhb.22898
• 发表时间: 2017-01
• 期刊: American journal of human biology : the official journal of the Human Biology Council
• 作者: Brown JC;Harhay MO;Harhay MN
• 通讯作者: Harhay MN

The Prognostic Importance of Frailty in Cancer Survivors.

• DOI: 10.1111/jgs.13819
• 发表时间: 2015-12
• 期刊: Journal of the American Geriatrics Society
• 影响因子: 6.3
• 作者: Brown JC;Harhay MO;Harhay MN
• 通讯作者: Harhay MN

Development of a risk-screening tool for cancer survivors to participate in unsupervised moderate- to vigorous-intensity exercise: results from a survey study.

• DOI: 10.1016/j.pmrj.2014.09.003
• 发表时间: 2015-02
• 期刊: PM&R
• 影响因子: 2.1
• 作者: Brown, Justin C.;Ko, Emily M.;Schmitz, Kathryn H.
• 通讯作者: Schmitz, Kathryn H.

Anthropometrically predicted visceral adipose tissue and blood-based biomarkers: a cross-sectional analysis.

人体测量预测内脏脂肪组织和血液生物标志物：横断面分析。

• DOI: 10.1007/s00394-016-1308-8
• 发表时间: 2018-03
• 期刊: European journal of nutrition
• 影响因子: 5
• 作者: Brown JC;Harhay MO;Harhay MN
• 通讯作者: Harhay MN