Oxygen Nanobubble Drink Impact on Exercise in Pulmonary Fibrosis

In Vivo Double-blind, Randomized, Placebo Controlled, Crossover Investigation of the Effect of Oral Administration of Oxygen Nanobubbles on the Distance Covered in a 6 Minute Walk Test in Patients With Pulmonary Fibrosis

Approximately 1 in 5 (or 12.7 million adults) in the UK have longstanding respiratory illnesses, and 6.5 million patients report taking prescription medication to ease the burden. Many patients suffer from lung tissue damage, which impairs adequate blood oxygenation and reduces blood saturations, and causes breathlessness. The current method of treatment is palliative - with the patient breathing supplemental oxygen through an oxygen cylinder and tube. This severely compromises patients' quality of life, as they are tethered to a heavy, unwieldy oxygen cylinder, limiting their ability and willingness to leave home.

Several recent studies in both animals and humans have indicated that orally administered oxygenated nanobubbles is a safe intervention that can improve tissue oxygenation. This randomized, double-blinded, cross-over, placebo-controlled study will evaluate the effect of an oxygen nanobubbles drink on the exercise performance of patients with chronic lung disease, such as pulmonary fibrosis. Patients will conduct the 6 Minute Walk Test (6MWT) twice, once with a placebo drink and once with the oxygen nanobubbles drink, based on a double-blind randomization protocol, and this study will evaluate the distance walked, heart rate, oxygen levels, breathlessness, and time to recovery in both cases. The investigators hypothesize that drinking the oxygen nanobubbles drink will improve the delivery of oxygen to vital organs, improving the distance a patient can cover in the 6 Minute Walk Test by 30m, which is the minimum clinically important difference.

Study Overview

• Status: Completed
• Conditions: Pulmonary Fibrosis
• Intervention / Treatment: Dietary supplement: Oxygen Nanobubble; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Oxford University Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is Male or Female, aged 18 years or above
• Participant is willing and able to give informed consent for participation in the study.
• Patients diagnosed with Pulmonary Fibrosis as per ATS/ERS guidelines, and in whom the lung fibrosis is considered the dominant cause of symptoms (i.e. no severe other disease such as COPD or heart failure)
• The patient must be able to walk independently without a walking stick
• The patient can, in the view of their respiratory clinician, adequately participate in a 6MW test

Exclusion Criteria:

• Pregnant or breast feeding
• History of current neurological condition (e.g., epilepsy)
• Patient has consumed liquorice in the last 24 hours.
• Patients with TLCO <30%
• Patients with known unstable ischaemic heart disease or pulmonary hypertension
• Patients with a history of smoking in the previous 30 days
• Patients that are allergic or intolerant towards: Liquorice, Lecithin derived from soya or sunflower, Citric acid, Glycerol
• Patients with known severe Renal Dysfunction
• Patients with known severe Liver Dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxygen Nanobubble First; In this arm, the oxygen nanobubbles will be provided as a drink first. The oxygen nanobubbles mixture will be mixed with water and oxygenated. This will be provided as a one-time 200ml drink 10 minutes before the start of the 6 minute walk test. In this arm, the placebo will be provided as the second drink. This will be provided after atleast 2 hours after the first 6 minute walk test is completed. The placebo mixture will be mixed with water and oxygenated. This will be provided as a one-time 200ml drink 10 minutes before the start of the 6 minute walk test.	Dietary supplement: Oxygen Nanobubble; This intervention consists of oxygenated nanobubbles made from lecithin with natural flavourings (liquorice, glycerol and citric acid); Other: Placebo; The placebo does not contain nanobubbles, and is made from natural flavourings (liquorice, glycerol and citric acid).
Placebo Comparator: Placebo First; In this arm, the placebo will be provided as a drink first. The placebo mixture will be mixed with water and oxygenated. This will be provided as a one-time 200ml drink 10 minutes before the start of the 6 minute walk test. In this arm, the oxygen nanobubbles will be provided as the second drink. This will be provided after atleast 2 hours after the first 6 minute walk test is completed. The oxygen nanobubbles mixture will be mixed with water and oxygenated. This will be provided as a one-time 200ml drink 10 minutes before the start of the 6 minute walk test.	Dietary supplement: Oxygen Nanobubble; This intervention consists of oxygenated nanobubbles made from lecithin with natural flavourings (liquorice, glycerol and citric acid); Other: Placebo; The placebo does not contain nanobubbles, and is made from natural flavourings (liquorice, glycerol and citric acid).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Minute Walk Distance	Distance covered in 6 Minute Walk Test (6MWT) with oxygen nanobubbles drink compared with placebo drink	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breathlessness	Changes in the Modified Borg score before and after the 6MWT with oxygen nanobubbles drink compared with placebo drink The Modified Borg (mBORG) scale from 0-10, with a higher score denoting less breathlessness and a better patient outcome.	1 day
Heart Rate	Heart Rate changes in 6MWT with oxygen nanobubbles drink compared with placebo drink	1 day
Oxygen Saturation	SpO2 changes in 6MWT with oxygen nanobubbles drink compared with placebo drink	1 day
Recovery Time	Time for SpO2 and HR to reset to resting levels after 6MWT with oxygen nanobubbles drink compared with placebo drink	1 day
Patient Perception of Exercise Ability	Patient self-reporting via patient questionnaire the additional distance they believe they can walk after 6MWT with oxygen nanobubbles drink compared with placebo drink	1 day

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Oxford University Hospitals NHS Trust
• Investigators: Principal Investigator: Najib Rahman, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2023
• Primary Completion (Actual): August 8, 2023
• Study Completion (Actual): August 9, 2023

Study Registration Dates

• First Submitted: January 16, 2023
• First Submitted That Met QC Criteria: January 30, 2023
• First Posted (Actual): February 2, 2023

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis
• Other Study ID Numbers: 308993

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No