PURPOSE:
The primary purpose of this study is to determine the effects of dietary nitrate
supplementation on submaximal cycle exercise performance in patients with fibrotic ILD.
HYPOTHESIS:
Our primary hypothesis is that dietary nitrate supplementation will result in greater
improvement in submaximal cycle exercise endurance time compared with placebo.
JUSTIFICATION:
Fibrotic interstitial lung disease (ILD) is a heterogeneous group of disorders that cause
scarring/fibrosis or inflammation of the lungs, resulting in significant morbidity and
high mortality. Almost all ILDs are characterized by dyspnoea and functional limitation
and there are few effective and/or well-tolerated pharmacotherapies for many ILD
subtypes.
Exertional dyspnoea leads to reduced exercise capacity in ILD, and this functional
limitation is further worsened by skeletal muscle weakness and dysfunction. Both dyspnoea
and poor exercise tolerance are strongly associated with quality of life and mortality in
ILD and thus improving dyspnoea and functional capacity are important goals in the
management of ILD.
Pulmonary rehabilitation is a structured evidence-based exercise and education
intervention that is recommended for most patients with ILD. Pulmonary rehabilitation
improves dyspnoea, functional capacity, and quality of life in patients with ILD;
however, these benefits are often modest and only temporary. The exercise component of
pulmonary rehabilitation is the predominant mediator of benefit; however, there are no
studies that have investigated the optimal method of exercise training in patients with
ILD. Thus, there is a clear need to identify new strategies that can provide larger and
more persistent benefits from pulmonary rehabilitation.
Nitric oxide (NO) is a physiological signaling molecule that plays a critical role in
vascular control. There is accumulating evidence that dietary nitrate, consumed in the
form of beetroot juice, can increase the bioavailability of NO and subsequently enhance
exercise performance in healthy, elite athlete, as well as diseased populations. These
improvements may be related, but not limited to, enhanced efficiency of locomotion,
peripheral locomotor oxygen delivery, and/or muscle power. The specific effects of
dietary nitrate supplementation in ILD patients has yet to be explored. However, there is
great potential for the use of this dietary supplement to improve exercise tolerance
during, and improve patient outcomes from, pulmonary rehabilitation.
STATISTICAL ANALYSIS:
A p value <0.05 will be considered significant for all analyses. Data analysis will be
performed using Microsoft Excel 2013 (Microsoft Corporation, Redmond, Washington, US) and
Stata v12 (StataCorp, Texas, US).
Primary outcome: The primary outcome of cycle endurance time will be based on the
duration patients were able to exercise during the constant work rate exercise test. A
t-test will be used to compare endurance times between the intervention and placebo
conditions.
The investigators have chosen to power this study based on the primary outcome of change
in cycle exercise endurance time. Based on previously collected data in our laboratory in
patients with ILD that show a standard deviation of 289.96 seconds for a 75% constant
work rate cycle exercise test with a conservative between test correlation of 0.90, the
investigators calculated that 15 participants would be needed to detect the minimal
clinically important difference of 105 seconds between conditions assuming a two-sided α
of 0.05 and 80% power.