An interventional study of nitrate-rich beetroot juice (70ml with approx. 400 mg nitrate) twice a day for 3 days in Idiopathic Pulmonary Fibrosis and Interstitial Lung Disease, sponsored by University Hospital Southampton NHS Foundation Trust. Recruiting at 1 site in United Kingdom. Open to participants aged 18 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-06.
Sponsored by University Hospital Southampton NHS Foundation Trust · Not applicable, Interventional, and Treatment
Idiopathic pulmonary fibrosis (IPF) is a type of scarring (fibrotic) lung disease. Reduced exercise capacity is a key symptom experienced by patients. In previous research the investigators identified that an interval-based exercise programme led to significant improvements in exercise capacity (Wallis et al Antioxidants. 2023).
An unexpected finding was that in patients with IPF, exercise led to a reduction in blood nitrite concentrations an observation the investigators did not see in non-affected individuals. Research has identified that nitrite concentrations are expected to increase after exercise and the size of this increase is related to an individual's exercise capacity. There is also evidence from healthy individuals and patients with chronic obstructive pulmonary disease (COPD) that nitrate supplementation (a source of nitrite) improves response to exercise training. However, in both these groups an exercise-induced fall in blood nitrite concentrations has not been observed. Hence our finding of an exercise-induced fall in blood nitrite levels in IPF patients suggest that they may be especially sensitive to supplementation with nitrate, commercially available as nitrate-rich beetroot juice (NRBJ).
This current study investigates this in a pilot placebo-controlled, double-blind, randomised, cross-over study of NRBJ on exercise capacity in IPF patients.
Aims In patients with IPF
A cohort (n=8) of age, sex-matched controls without IPF will be enrolled for comparison of forearm blood flow and pre-exercise venous blood samples for biomarkers comparison only.
Number of sites: 1
Idiopathic pulmonary fibrosis (IPF) is the prototypic chronic progressive fibrotic interstitial lung disease (ILD). Progressive disease is characterised by breathlessness and exercise limitation and there is an unmet need for interventions which improve patient's quality of life. Increasing exercise intolerance in patients with ILD is associated with worsening quality of life and loss of independence. Pulmonary rehabilitation is recommended by the National Institute for health and Care Excellence (NICE) for patients with ILD, however individual responses to exercise training are variable and optimal training strategies are yet to be established.
In previous published research (Wallis et al. 2023. Antioxidants) the investigators studied the effect of an individually prescribed, interval-based aerobic exercise programme on redox status and functional capacity in patients with IPF. At baseline, IPF patients had evidence of increased oxidative stress. The individually prescribed exercise programme led to a significant increase in antioxidant buffering capacity together with clinically meaningful improvements in exercise capacity and medical research council (MRC) breathlessness score. Notably, the investigators also identified that in patients with IPF, exercise induced a significant fall in circulating nitrite concentrations, an effect potentiated by exercise training. In contrast, control individuals exhibited a post-exercise increase in nitrite concentrations due to shear stress-induced nitric oxide (NO)-synthase stimulation.
Nitric oxide (NO) physiology is strongly implicated in the physiology of exercise performance. In healthy individuals the delta of the post-exercise increase in circulating nitrite concentration positively correlates with peak exercise capacity and it has been identified that supplementation with nitrate significantly lowers the oxygen cost (oxygen uptake [V̇O2] required to perform a given work-rate) of submaximal exercise. Recent evidence from patients with COPD has identified that sustained supplementation with nitrate-rich beetroot juice augmented the effect of pulmonary rehabilitation compared to placebo (+30m in incremental shuttle walk test). However, in contrast to our findings in IPF, within these groups no underlying dysregulation in nitrite utilisation during exercise has been identified i.e. exercise induced nitrite decrease is not present. This suggests that patients with IPF may be exquisitely sensitive to benefit from nitrate (known to serve as a source of nitrite) during exercise, a non-pharmacologic intervention with potential rapid translation into clinical practice.
Hypothesis
Nitrate supplementation (in the form of nitrate-rich beetroot juice drink) significantly improves submaximal exercise capacity in patients with IPF.
Here the investigators test this hypothesis in this study by way of a pilot randomised controlled double-blind cross-over study of nitrate supplementation on submaximal exercise capacity in patients with IPF. Together with a nested mechanistic study investigating the effect of nitrate supplementation on systemic blood markers of nitric oxide production and metabolism as well as forearm blood flow.
Aims and Objectives
In patients with IPF
Study Design and setting Up to 8 patients with IPF will be recruited to this single centre cohort cross-over double-blind designed pilot study at a large NHS Foundation trust teaching hospital. Ongoing interim analysis will be conducted throughout the study.
Intervention Participants will be randomly assigned to either 3-days (two times daily) of nitrate-rich beetroot juice drink (daily dose of nitrate 800mg nitrate) or nitrate-depleted juice placebo control drink of identical taste and colour (Treatment Period 1) immediately prior to constant-load exercise test (see intervention). Following a wash-out period of at least 1-week they will cross-over and repeat (Treatment Period 2).
Control Cohort:
A cohort (n=8) of age and sex-matched controls without IPF will be enrolled for comparison of forearm blood flow by venous occlusion digital thermal imaging and pre-exercise venous blood samples for biomarkers of NO metabolism and oxidative stress.
End points: Endurance time, adverse events. Number of sites: 1
IPF Patients: Inclusion Criteria
IPF Patients: Exclusion Criteria
Controls: Inclusion Criteria
1) Age and sex-matched to participants in the IPF cohort. Note: the participants will be age-matched within a 5-year age bracket.
Controls: Exclusion Criteria
Treatment period 1) nitrate-rich beetroot juice (70ml with approx. 400 mg nitrate) twice a day for 3 days Treatment period 2) placebo nitrate-depleted beetroot juice (70ml) twice a day for 3 days
Dietary Supplement: nitrate-rich beetroot juice (70ml with approx. 400 mg nitrate) twice a day for 3 days
Treatment period 1) placebo nitrate-depleted beetroot juice (70ml) twice a day for 3 days Treatment period 2) nitrate-rich beetroot juice (70ml with approx. 400 mg nitrate) twice a day for 3 days
Dietary Supplement: nitrate-rich beetroot juice (70ml with approx. 400 mg nitrate) twice a day for 3 days
commercially available beetroot juice dietary nitrate supplement
endurance time
fixed-load static cycle ergometry test
Time frame: From end of treatment period 1 to end of treatment period 2 (minimum 10 days)
plasma nitrate and nitrite concentrations
venous blood samples
Time frame: From end of treatment period 1 to end of treatment period 2 (minimum 10 days)
forearm blood flow
venous occlusion digital thermal imaging
Time frame: From end of treatment period 1 to end of treatment period 2 (minimum 10 days)
Plan to share: No
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Idiopathic Pulmonary Fibrosis→
University Hospital Southampton NHS Foundation Trust