Effect of Inhaled Hydroxy Gas on Long COVID Symptoms

Study Overview
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Brief Summary
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The goal of this clinical trial is to see if several weeks of self-administered, home-based, treatment involving breathing hydroxy gas (a mixture of hydrogen and oxygen) for at least 2 hours a day for 3 weeks, will relieve symptoms in patients suffering from Long COVID. The main question it aims to answer is whether inhaling hydroxy gas might be a useful treatment option to help patients with long COVID cope better and recover quicker from this condition. Participants will wear a nasal canula (placed in their nostrils) to inhale a gas from a machine that they will be trained to use at home. In one 3-week period, the machine will deliver hydroxy gas (treatment) and in a separate 3-week period the machine will deliver normal air (placebo). The order of the treatment or placebo periods will be randomized and separated by a minimum of 3-weeks during which the participants will not use the machine ('washout' period). Neither the participant nor the investigators will know which 3-week period is the treatment and which is the placebo phase. Participants will visit the laboratory (or be tested at home) at the start and end of each 3-week period. Testing will involve measuring physical ability (handgrip strength, how far they can walk in 6 minutes, how many times they can stand up and sit down in a minute), breathing problems (how hard they can blow out, how breathless they feel), cognitive ability (how quickly they can mark out a trail based on numbers and letters), and state of mind (mood). The investigators hypothesize that compared to inhaling placebo, inhaling the hydroxy gas will produce greater improvement in physical ability, relieve breathing problems, and enhance cognitive ability and mood, thereby showing that it can relieve key symptoms of long COVID

Official Title
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Randomised, Placebo-controlled, Double-blind Cross-over Study to Investigate the Therapeutic Effects of an Inhaled Hydrogen/Oxygen Mixture to Improve Long COVID Symptoms

Conditions
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Post-Acute COVID-19 Syndrome

Intervention / Treatment
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* Device: Hydroxy gas


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any moderate or severe pain, breathlessness, or fatigue associated with long COVID live within an hour's drive of the Oxford Brookes campus Exclusion Criteria: Pre-existing secondary diseases; tumors, mental health conditions, chronic respiratory conditions such as Chronic Obstructive Pulmonary Disease (COPD), and cardiac disease Previous requirement of ICU treatment due to COVID Acute or chronic infections or no pre-existing autoimmune diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will be randomly assigned a machine that delivers either hydroxy or placebo gas in the first three weeks of the study. Those who receive placebo in the first three weeks will receive hydroxy in the last three weeks following a minimum of a 3 week washout period. Those who receive hydroxy in the first three weeks will receive placebo in the last three weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment-Placebo arm<br>The participants in this arm are given a machine that produces hydroxy gas in the first three weeks. In the final three weeks of the study, they will use a machine that produces a placebo gas. | Device: Hydroxy gas<br>* Hydroxy gas is a combination of hydrogen and oxygen together.<br>|
| Other: Placebo-treatment arm<br>The participants in this arm are given a machine that produces a placebo gas in the first three weeks. In the final three weeks of the study, they will use a machine that produces hydroxy gas. | Device: Hydroxy gas<br>* Hydroxy gas is a combination of hydrogen and oxygen together.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breathlessness | Total dyspnoea score in the preceding 2 weeks, quantified from the D-12 questionnaire (% maximum score). Sample size estimate was based on this measure. | Week 0 and Week 4 (just before and after the first 3 week period of home-administration), Week 6 and week 10 (just before and after the start of the second 3 week period of home-administration). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exertional dyspnea | Change in total dyspnoea score from rest to peak exercise quantified using the D12 questionnaire | Week 0 and Week 4 (just before and after the first 3 week period of home-administration), Week 6 and week 10 (just before and after the start of the second 3 week period of home-administration) | 
| Physical capacity (muscle fatigue) | (i) Distance walked at their own pace during the 6-minute walk test and the number of sit to stands achieved in 1 minute. (ii) Handgrip strength measured using a hand dynamometer as the maximum squeeze (kg) sustained for 5 second (iii) Peak expiratory flow rate (PEF) achieved by blowing into a Wright's peak flow meter as hard as possible (Liters per minute) | Week 0 and Week 4 (just before and after the first 3 week period of home-administration), Week 6 and week 10 (just before and after the start of the second 3 week period of home-administration) | 
| Psychological state and cognitive ability | (i) Mood cluster scores for sedation, discontentment, and tension derived from the Bond Lader mood questionnaire (%full scale) (ii) Time taken to complete a trail marking task based on joining sequential numbers and/or letters | Week 0 and Week 4 (just before and after the first 3 week period of home-administration), Week 6 and week 10 (just before and after the start of the second 3 week period of home-administration) | 
| General long COVID symptom burden | Overall % score on the long COVID Symptom Burden Questionnaire | Week 0 and Week 4 (just before and after the first 3 week period of home-administration), Week 6 and week 10 (just before and after the start of the second 3 week period of home-administration) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-Acute COVID-19 Syndrome, Long COVID, Long Haul COVID-19, Long-Haul COVID, Post-Acute Sequelae of COVID Infection