Assessing the Impact of Tiotropium on Lung Function and Physical Activity in GOLD Stage II COPD Patients who are Naïve to Maintenance Respiratory Therapy: A Study Protocol

Abstract

Physical activity status is increasingly recognized as a reliable predictor of mortality and hospitalization in patients with chronic obstructive pulmonary disease (COPD). The reduction in physical activity occurs earlier in the clinical course of COPD than previously appreciated, possibly arising from breathlessness, reduced exercise tolerance, and adoption of a more sedentary lifestyle. To date, no clinical trial has evaluated the impact of pharmacotherapy on both lung function and physical activity. We recently designed a study that evaluates the impact of tiotropium (a once-daily inhaled anticholinergic) on lung function and physical activity in a maintenance/treatment-naïve Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage II COPD cohort. Previous studies have demonstrated that tiotropium improves lung function and exercise tolerance; whether these benefits translate into improvements in physical activity is the focus of the current work. Here we describe the rationale and challenges in developing and implementing this study and review its unique features and novel design, including: utility of direct activity monitoring in multicenter clinical trials; importance of behavioral-modification techniques (including motivational interviewing to improve patient self-efficacy and adherence for a healthy, more active lifestyle); utility of individualized activity plans that provide an integrated approach with pharmacotherapy and behavioral modification to help patients achieve a more active lifestyle.

Keywords: COPD; activity monitor; methodology; physical activity; study design.; tiotropium.

Fig. (1)

Study design. The study consists of nine clinic visits (V1-V9) over 28 weeks. There is a 4-week screening period that includes Visit 1/Week –4 with single-blind placebo run-in at Visit 2/Week –3; and a 24-week double-blind phase that includes Visit 3/Week 0 (baseline), Visit 4/Week 4, Visit 5/Week 8, Visit 6/Week 12, Visit 7/Week 16, Visit 8/Week 20 and Visit 9/Week 24 (end of the study).

Fig. (2)

Activity plan for (A) all patients and (B) active patients. Panel A – Patients are encouraged to walk or cycle at a “moderate” Modified BORG (CR-10) Score for breathlessness (3/10 to 4/10). *Patients whose physical activity exceeds 30 minutes of activity >3 METS five days a week, and who want to further increase their physical activity, proceed to Panel B. Panel B – Patients are considered active if they exceed 30 minutes of physical activity >3 METS five days a week. *Options for advancing activity level include: 1) increase the time spent walking/cycling in increments of 5-10 minutes 5/7 days and/or walking more briskly; 2) gradually increase activity to 6/7 days; or 3) focus on lifestyle adjustments (e.g. use stairs instead of elevator).