Effects of a Partially Supervised Conditioning Program in Cystic Fibrosis: An International Multicenter, Randomized Controlled Trial (ACTIVATE-CF)

Abstract

Rationale: The long-term effects of vigorous physical activity (PA) on lung function in cystic fibrosis are unclear. Objectives: To evaluate effects of a 12-month partially supervised PA intervention using motivational feedback. Methods: In a parallel-arm multicenter randomized controlled trial (ACTIVATE-CF), relatively inactive patients aged at least 12 years were randomly assigned (1:1 ratio) to an intervention group or control group. The intervention group consented to add 3 hours of vigorous PA per week, whereas the control group was asked not to change their PA behavior. Primary endpoint was change in percent predicted FEV₁ (ΔFEV₁) at 6 months. Secondary endpoints included PA, exercise capacity, exercise motives, time to first exacerbation and exacerbation rates, quality of life, anxiety, depression, stress, and blood glucose control. Data were analyzed using mixed linear models. Measurements and Main Results: A total of 117 patients (40% of target sample size) were randomized to an intervention (n = 60) or control group (n = 57). After 6 months, ΔFEV₁ was significantly higher in the control group compared with the intervention group (2.70% predicted [95% confidence interval, 0.13-5.26]; P = 0.04). The intervention group reported increased vigorous PA compared with the control group at each study visit, had higher exercise capacity at 6 and 12 months, and higher PA at 12 months. No effects were seen in other secondary outcomes. Conclusions: ACTIVATE-CF increased vigorous PA and exercise capacity, with effects carried over for the subsequent 6 months, but resulted in better FEV₁ in the control group.

Keywords: cystic fibrosis; exercise capacity; exercise program; physical activity; randomized controlled trial.

Figure 1.

The consolidated standards of reporting trials flow diagram through the ACTIVATE-CF trial. *In four participants of the control group, no valid FEV₁ measurement was available at 6 months. eCRF = electronic case report form; ITT = intention to treat; PI = principal investigator; Prim. = primary.

Figure 2.

Change in FEV₁ (ΔFEV₁) in percent predicted from baseline. (A) Individual changes from baseline to 6 months (primary outcome). There was a significant difference between groups in favor of the control group (mean difference, 3.18% predicted [95% confidence interval, 0.39–5.97]; P = 0.026). (B) Changes in FEV₁ from baseline to visits at 3, 6, 9, and 12 months. Only the actually measured data are shown. The numbers in parentheses are the respective sample sizes. (C) Intention-to-treat analysis including imputed data. Error bars in (B) and (C) are standard errors.

Figure 3.

Changes in (A) reported vigorous physical activity (VPA) (control group: n = 57; intervention group: n = 60); (B) aerobic steps (control group: n = 50; intervention group: n = 51); (C) peak work rate (ΔWpeak) (control group: n = 50; intervention group: n = 53), and (D) peak oxygen uptake (Δ$\dot{\mathrm{V}}{\mathrm{o}}_2$ peak) (control group: n = 50; intervention group: n = 53). The graphs are based on full datasets with imputed data (intention-to-treat analyses). **P < 0.01 and ***P < 0.001. Error bars are standard errors.

Figure 4.

Time to first exacerbation in the intervention and the control group.