I-Walk-CRC - Feasibility and Efficacy of Interval Walking in Patients With Colorectal Cancer

INTRODUCTION More than 30.000 individuals are living with a colorectal cancer (CRC) diagnosis in Denmark today. Due to marked advances in surgical and medical treatment, as well as novel screening programs, this number is expected to increase over the coming years. Numerous studies have shown that physical activity is inversely associated with colorectal cancer risk. A meta-analysis of 52 studies found that regular participation in physical activity reduced disease risk by 24% (HR: 0.76 , 95%Confidence Interval [95%CI]: 0.72 - 0.81). Recent evidence furthermore shows that physical activity after a CRC diagnosis is a strong independent predictor for overall survival, CRC-specific survival, and survival after disease relapse. CRC patients who adhere to the current recommendation of at least 150 min moderate intensity physical activity per week have an estimated 10-40% lower CRC-specific and 20-50% lower overall mortality risk in comparison to sedentary counterparts. The causative mechanisms responsible for this protective effect are not fully elucidated, but several studies have shown that metabolic health factors, i.e. overweight/adiposity, systemic levels of glucose, insulin, Insulin-like Growth Factor (IGF)-1, leptin, adiponectin and inflammatory cytokines (TNF-α, CRP) are associated with CRC prognosis. These factors are, under normal circumstances modifiable through physical activity and exercise, which may constitute a plausible mode of action, through which, exercise may reduce risk of disease progression as well as development and/or progression of cardio-metabolic co-morbid disorders.

BACKGROUND Over the last decade, more than 70 studies have explored the capacity of physical exercise to improve physiological (fitness, muscle strength, body composition) and psychosocial (fatigue, depression, emotional well-being) outcomes in patients with cancer during and after anti-neoplastic therapy and although CRC is among the most prevalent malignancies, few exercise-trials have been performed in this patient group. The reason for this notable low number of studies, relative to other common cancers in particular breast and prostate cancer, may be a number of disease and treatment specific phenomena, e.g. high prevalence of co-morbidities, stoma, late-effects from surgery or adjuvants therapies etc., which may complicate participation in traditional hospital-based exercise-programs, which is often comprised of fitness- and strength-training. A recent meta-analysis included just 3 randomized trials investigating exercise in CRC patients, and found positive effects exercise vs control on cardiovascular fitness; standardized mean difference: 0.59 [95%CI 0.25-0.93], P<0.01. A recent pilot study furthermore showed that home-based exercise improved several metabolic factors including reduction in body weight, plasma insulin levels and improved insulin sensitivity. Thus, these data indicate that CRC patients can improve cardio-metabolic health profile by physical exercise; however, the present body of research have included a total of less than 200 patients; explored various exercise-modalities, and applied inconsistent and/or indirect assessment-methods. To this end, there is a remaining need for high quality evidence describing effective exercise-interventions in CRC patients, particularly interventions aimed to be successfully implemented in clinical practice in case of positive results.

Interval training, as characterized by inter-changing cycles of high and low intensity exercise, have long been recognized as the most effective exercise-modality to improve cardiopulmonary fitness, and can furthermore induce equal or greater metabolic effects than continuous exercise over longer duration. Considerable challenges exists however, when performing high intensity interval exercise-training in clinical settings. This type of exercise often needs to be performed on ergometer bicycles or treadmills and organized as supervised, hospital-based training to ensure proper monitoring and feedback to participants for optimal exercise intensity and progression, which limits the dissemination potential beyond the trial period.

Center for Physical Activity Research (CFAS) have performed a number of trials showing that interval training can be performed as free-living interval-walking, consisting of repeating cycles of 3 minutes fast walking followed by 3 minutes slow walking with significant positive effects in cardio-metabolic health profile. Our studies show, that 16 weeks of interval-walking improved VO2peak (+4ml /kg/min) reduced bodyweight (-4 kg) and fat mass (-3 kg) in patients with type 2 diabetes. Moreover, interval-walking improved plasma lipid-profile, glucose metabolism and insulin sensitivity, in contrast to continuous walking, which was matched for training-volume and energy expenditure. In parallel with these intervention-studies, a smart-phone application, called InterWalk (www.InterWalk.dk), has been developed, which can deliver this training program of repeating cycles: 3 minutes fast walking followed by 3 minutes slow walking. The exercise-program is based on an individualized test-function with live-feedback, ensuring proper exercise-intensities (walking-speed), and can simultaneously store test- and training data (exercise-time, walking-speed, distance etc.) to an external server for research purposes. Preliminary data shows that three months home-based interval-walking using the InterWalk-application can improve fitness by ~10%. Thus, our preliminary data shows InterWalk can deliver an un-supervised, yet individualized, structured and objectively monitored exercise-program which can effectively improve cardio-metabolic health, and may be more applicable and feasible, compared to traditional hospital-based programs in stigmatized patient groups with major co-morbid complications.

The investigators therefore propose this intervention can have a great health promoting potential in patients with CRC; however previous work have found considerable barriers and complications associated with successful participation in exercise-programs for this patient group. Thus, the investigators intend to explore whether interval-walking, delivered by the InterWalk-app, is safe and feasible, and furthermore the investigatorsintend to explore if the intervention can cause similar positive effects as the investigators have seen previously in other clinical populations.