Pilot Study of Nitrate-rich Beetroot Juice Supplementation in Patients With Idiopathic Pulmonary Fibrosis (IPF)

NCT06488638 | Not Yet Recruiting

• 1 other identifier: RHMRESP0009
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

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 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

• Quantify the effect of nitrate supplementation on exercise capacity
• Determine the effect of nitrate supplementation on blood markers of nitric oxide production/metabolism.
• Determine the effect of nitrate supplementation on forearm blood flow. Sample size: n=8 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 (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

Conditions

Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease

Outcome Measures

Primary Outcomes (1)

• endurance time

  fixed-load static cycle ergometry test

  From end of treatment period 1 to end of treatment period 2 (minimum 10 days)

Secondary Outcomes (2)

• plasma nitrate and nitrite concentrations

  From end of treatment period 1 to end of treatment period 2 (minimum 10 days)

• forearm blood flow

  From end of treatment period 1 to end of treatment period 2 (minimum 10 days)

Study Arms (2)

Group A

EXPERIMENTAL

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

Group B

PLACEBO COMPARATOR

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

Interventions

nitrate-rich beetroot juice (70ml with approx. 400 mg nitrate) twice a day for 3 days DIETARY_SUPPLEMENT

commercially available beetroot juice dietary nitrate supplement

Group A; Group B

Eligibility Criteria

• Age: 28 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-85 years with a prior specialist multidisciplinary team diagnosis of idiopathic pulmonary fibrosis (IPF) based on current established consensus guidelines.
• Medical Research Council (MRC) breathlessness grade 1-3
• Judged clinically stable for 3 months prior to recruitment by the investigator.

You may not qualify if:

• Baseline spirometry with FEV1/FVC ratio \< 0.7.
• Neoplastic disease undergoing treatment or active follow up.
• Presence of infection or exacerbation requiring hospitalization, within last 3 months.
• Current tobacco smoker or use of nicotine containing vapes (within 3months)
• Current use of ambulatory or long-term oxygen therapy (LTOT).
• Peripheral oxygen saturations \<85% during 6-minute walk-test.
• Any condition which would prevent completion of cycle-ergometer testing, pulmonary function testing (PFT) or 6-minute walk testing as judged by the investigator.
• Participation in a pulmonary rehabilitation (PR) program in the last 3 months.
• Any condition excluding CPET based on the absolute contraindication as the ACCP/ATS guidelines 2003
• Positive pregnancy test in females of childbearing age.
• Symptomatic peripheral vascular disease
• Inability to give informed written consent
• Malignancy (except localized squamous or basal cell skin carcinoma) undergoing active investigation, treatment, or follow-up
• Significant cardiorespiratory disease as judged by the investigator
• Diabetes mellitus requiring treatment with pharmacology therapy

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• NIHR Southampton Respiratory Biomedical Research Centre: collaborator
• Asthma, Allergy and Inflammation Research (AAIR) Charity: collaborator

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial

Interventions

Nitrates

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Anions; Ions; Electrolytes; Inorganic Chemicals; Nitric Acid; Nitrogen Compounds; Organic Chemicals

Study Officials

• Tim JM Wallis, MD, PhD

  University Hospital Southampoton

  STUDY CHAIR

Central Study Contacts

Tim JM Wallis, MD, PhD

CONTACT

0231204479; tim.wallis@uhs.nhs.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: placebo-controlled, double blind, randomised controlled trial

Study Record Dates

• First Submitted: June 26, 2024
• First Posted: July 5, 2024
• Study Start: September 1, 2024
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share