Ignite Creation Date:
2024-07-17 @ 11:12 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06488638
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-05
First Post:
2024-06-26
Brief Title:
Pilot Study of Nitrate-rich Beetroot Juice Supplementation in Patients With Idiopathic Pulmonary Fibrosis IPF
Sponsor:
University Hospital Southampton NHS Foundation Trust
Organization:
University Hospital Southampton NHS Foundation Trust
Study Overview
Official Title:
Pilot Study of Nitrate-rich Beetroot Juice Supplementation in Patients With Idiopathic Pulmonary Fibrosis IPF
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BEET-IPF
Brief Summary:
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 individuals 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
Quantify the effect of nitrate supplementation on exercise capacity
Determine the effect of nitrate supplementation on blood markers of nitric oxide productionmetabolism
Determine the effect of nitrate supplementation on forearm blood flow Sample size n8 IPF patients aged 18-85years and medical research breathlessness scale 1-3 Intervention 3-days two-times daily NRBJ or nitrate-depleted placebo juice both commercially available with subsequent constant-load exercise test Primary outcome Following at least 1 week wash-out period participants will cross-over and repeat
A cohort n8 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
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 individuals 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
Quantify the effect of nitrate supplementation on exercise capacity
Determine the effect of nitrate supplementation on blood markers of nitric oxide productionmetabolism
Determine the effect of nitrate supplementation on forearm blood flow Sample size n8 IPF patients aged 18-85years and medical research breathlessness scale 1-3 Intervention 3-days two-times daily NRBJ or nitrate-depleted placebo juice both commercially available with subsequent constant-load exercise test Primary outcome Following at least 1 week wash-out period participants will cross-over and repeat
A cohort n8 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
Detailed Description:
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 patients 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 VO2 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 ie 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
1 Quantify the effect of nitrate supplementation on submaximal exercise capacity constant work-rate test
2 Determine the effect of nitrate supplementation on markers of nitric oxide NO production and metabolism pre- and post-exercise
3 Determine the effect of nitrate supplementation on forearm blood flow
4 Assess the effect of nitrate supplementation of participants perceptions of exercise and quality of life
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 n8 of age and sex-matched controls without IPF will be enrolled for comparison of forearm blood flow by venous occlusion plethysmography VOP and pre-exercise venous blood samples for biomarkers of NO metabolism and oxidative stress
End points Endurance time adverse events Number of sites 1
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 VO2 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 ie 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
1 Quantify the effect of nitrate supplementation on submaximal exercise capacity constant work-rate test
2 Determine the effect of nitrate supplementation on markers of nitric oxide NO production and metabolism pre- and post-exercise
3 Determine the effect of nitrate supplementation on forearm blood flow
4 Assess the effect of nitrate supplementation of participants perceptions of exercise and quality of life
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 n8 of age and sex-matched controls without IPF will be enrolled for comparison of forearm blood flow by venous occlusion plethysmography VOP and pre-exercise venous blood samples for biomarkers of NO metabolism and oxidative stress
End points Endurance time adverse events Number of sites 1
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None