Oral nitrate supplementation to enhance pulmonary rehabilitation in COPD: ON-EPIC a multi-centre, double-blind, placebo-controlled, randomised parallel group study

Abstract

Rationale Dietary nitrate supplementation has been proposed as a strategy to improve exercise performance, both in healthy individuals and in people with chronic obstructive pulmonary disease (COPD). We aimed to assess whether it could enhance the effect of pulmonary rehabilitation (PR) in COPD. Methods This double-blind, placebo-controlled, parallel group, randomised controlled study performed at four UK centres, enrolled adults with GOLD grade II-IV COPD and MRC dyspnoea score 3-5 or functional limitation to undertake a twice weekly eight week PR programme. They were randomly assigned (1:1) to either 140mls of nitrate-rich beetroot juice (BRJ) (12.9mmol nitrate), or placebo nitrate-deplete BRJ, consumed three hours prior to undertaking each PR session. Allocation used computer generated block randomisation. Measurements The primary outcome was change in incremental shuttle walk test (ISWT) distance. Secondary outcomes included quality of life, physical activity level, endothelial function via flow mediated dilatation, fat free mass index and blood pressure parameters. Main Results 165 participants were recruited, 78 randomised to nitrate-rich BRJ and 87 randomised to placebo. Exercise capacity increased more with active treatment (n=57) than placebo (n=65); median (IQR) change in ISWT distance +60m (10, 85) vs. +30m (0, 70), (p = 0.027). Active treatment also impacted on systolic blood pressure: Treatment group -5.0mmHg (-5.0, -3.0) vs control +6.0mmHg (-1.0, 15.5) (p<0.0005). No significant serious adverse events or side effects were reported. Conclusions Dietary nitrate supplementation appears to be a well-tolerated and effective strategy to augment the benefits of PR in COPD.