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（由申请人提供）：高复发率是促进结肠癌（CC）幸存者健康和长寿的关键障碍。减少这一障碍的方法是制定干预措施，以尽量减少 CC 幸存者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，诊断后体力活动水平的提高与无病生存率提高 42%、复发率降低 40% 以及 CC 特异性死亡率降低 45-71% 相关。然而，这种关联的潜在分子机制仍不清楚。表征促进现有肿瘤生长和循环肿瘤细胞 (CTC) 传播的生物标志物可能会增进对 CC 复发和进展的了解。细胞粘附分子在CC复发的发生和进展中发挥着关键作用。细胞粘附分子，例如可溶性细胞间粘附分子-1 (sICAM-1) 和可溶性血管粘附分子-1 (sVCAM-1)，促进现有微转移的生长和进展，并通过使 CTC 侵入细胞外基质、渗透和传播到整个血流来促进其他转移灶的形成，以及 外渗至远处器官。这项试点研究将 39 名 CC 幸存者随机分为三个同等规模的组：低剂量（每周 150 分钟-1）中等强度有氧运动组、高剂量（每周 300 分钟-1）中等强度有氧运动组或对照组，为期 26 周。将为参与者提供家用跑步机，以支持实现这些锻炼目标。我们的研究团队在规定这些有氧运动量方面取得了成功。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事件的可行性和发生率，并收集关于两种不同剂量的有氧运动对与 CC 复发和转移相关的两种细胞粘附生物标志物（sICAM-1 和 sVCAM-1）的生物学功效的初步证据。然后我们将探讨细胞粘附分子和 CTC 之间的关系。这一研究方向与国家癌症研究所 PAR-12-229 的当前使命以及具有挑战性的问题 PQA-5 相一致，其目的是阐明最佳的运动处方，以改善假设为身体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

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

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.