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Ambulatory Oxygen Therapy for Individuals With Mild-to-moderate Interstitial Lung Disease

Phase 2
Not yet recruiting
Conditions
Fibrotic Interstitial Lung Disease
Interventions
Drug: Exertional Oxygen
Behavioral: Education and Support
Registration Number
NCT06053164
Lead Sponsor
University of Alberta
Brief Summary

The investigators plan to conduct a study to find out if giving portable oxygen therapy (during physical activity) to patients with interstitial lung disease will improve quality of life, exercise tolerance, shortness of breath, and blood vessel function. Oxygen will be provided for a period of 8 weeks. Additionally, the investigators plan to investigate if it is helpful to deliver individualized support when providing oxygen therapy, through check-in phone calls with a respiratory therapist and by providing additional educational material.

Detailed Description

Brief Summary:

The investigators plan to conduct a study to find out if giving portable oxygen therapy (during physical activity) to patients with interstitial lung disease will improve quality of life, exercise tolerance, shortness of breath, and blood vessel function. Oxygen will be provided for a period of 8 weeks. Additionally, the investigators plan to investigate if it is helpful to deliver individualized support when providing oxygen therapy, through check-in phone calls with a respiratory therapist and by providing additional educational material.

Detailed Description:

BACKGROUND

Interstitial lung disease (ILD) is comprised of a group of pulmonary diseases that are characterized by inflammation and/or lung parenchymal fibrosis. Individuals with ILD may be normoxic at rest; however, underlying impairments in gas exchange can contribute to a reduction in oxygen saturation (SpO2) during exertion. Hypoxemia can cause inflammation and cardiovascular dysfunction, which could lead to cardiac events. A recent study found that 78% of ILD patients had cardiovascular comorbidity, which was predictive of death within this ILD cohort.

Oxygen therapy is used in patients with advanced lung disease with resting hypoxemia; however, there is limited evidence regarding its clinical efficacy. Furthermore, there is little support to describe the benefit of ambulatory oxygen therapy in individuals with lung disease who are normoxemic at rest but become hypoxemic with exertion. Accordingly, thresholds for the prescription of oxygen therapy vary between (and within) health districts and geographical regions, and individuals who might benefit from supplemental oxygen typically do not qualify for funding of oxygen therapy under unclear guidelines. Furthermore, data from studies in patients with chronic obstructive pulmonary disease (COPD) are often extrapolated for use in guiding oxygen therapy in patients with ILD, which is likely inappropriate considering recent research demonstrated that individuals with fibrotic ILD experience greater hypoxemia than those with COPD during the 6-minute walk test (6MWT).

Oxygen therapy may be beneficial in reducing inflammation, oxidative stress, and pulmonary artery pressure, all of which are elevated in ILD. Furthermore, a reduction in dyspnea during exercise with exertional oxygen therapy might increase daily physical activity, exercise tolerance, and reduce overall sedentary time, which would have a positive effect on vascular function. These postulated outcomes, however, are confounded by various practical, psychological, and social challenges associated with use of an oxygen concentrator, as well as challenges with proper titration of oxygen levels (accurately targeting appropriate SpO2) in relation to exertional intensity. Paradoxically, if the flow of oxygen is too high, activation of inflammatory and oxidative pathways may inhibit the benefits related to the alleviation of hypoxemia. Thus, integration of patient-specific disease support tools is essential when initiating oxygen therapy to ensure appropriate oxygenation during exertion.

OBJECTIVE To assess the feasibility of oxygen therapy, education, and support for individuals with fibrotic interstitial lung disease and exertional hypoxemia. As a secondary objective, the effects of exertional oxygen therapy and support on physical activity, vascular function, and health-related quality of life in individuals with fibrotic interstitial lung disease will be investigated.

PRIMARY AND SECONDARY ENDPOINTS

Health related quality of life as assessed by the EQ-5D-5L and the K-BILD Exercise tolerance, assessed by 6MWD while breathing room air Daily physical activity and sedentary time as assessed by a remote monitor. Dyspnea, as measured by the Dyspnea 12 questionnaire Cough using the visual analog scale (VAS) and cough score (measured by Leicester Cough Questionnaire; LCQ) Vascular function, measured by flow mediated dilation (FMD) of the brachial artery Pulmonary artery systolic pressure (PASP) measured by cardiac echocardiography Cardiac systolic and diastolic function assessed by cardiac echocardiography Systemic inflammation

STUDY DESIGN

Single-blind (assessment team) open-label randomized control

TRIAL TREATMENT

Participants will be randomized into one of three arms:

Control:

(Arm 1) 8 Weeks of usual care (n=20)

Treatment:

(Arm 2) 8 Weeks of supplemental oxygen(n=20)

(Arm 3) 8 Weeks of supplemental oxygen plus educational materials and scheduled support (n=20)

All: 2-week baseline prior to intervention and 2-week washout post-intervention to document carry-over effect of intervention.

DURATION

Seven sessions will be completed over a 13-week period.

TIMELINE

Visit 1) Participant enrollment, medical history, standard pulmonary function test (PFT) and 6-minute walk test (6MWT); followed by 1-week for collection of baseline physical activity and SpO2. During this visit, participants will be provided a wrist-worn activity monitor and a finger-worn pulse oximeter. This visit will take approximately 3 hours.

Visit 2) Doppler measurements of systemic vascular function (flow mediated dilation) will be measured at rest while breathing room air. A small sample of venous blood will be taken to analyze inflammatory levels and reactive oxygen species. Participants will fill out questionnaires relating to health-related quality of life, dyspnea, and cough. Finally, participants will perform tests of lung diffusing capacity for carbon monoxide (DLCO) under three different conditions: seated, supine, and during exercise at 40W on a cycle ergometer.

Visit 3) One to three days after Visit 2, participants will return for the second day of pre-intervention baseline testing. An echocardiographic exam will be completed to determine pulmonary artery systolic pressure as well as systolic and diastolic function in the left and right ventricles of the heart. To enhance the Doppler signal during the cardiac ultrasound, agitated saline contrast will be used. Two 6-minute walk tests will then be completed, separated by half an hour. This visit will take approximately 2 hours. Following this day, participants will be randomized into one of three arms for an 8-week intervention.

Eight-week intervention, randomized into one of:

* No oxygen

* Exertional oxygen

* Exertional oxygen + additional support

Visit 4) Repeat Day 2 protocol. Visit 5) Repeat Day 3 protocol.

Two-week washout period

Visit 6) Repeat Day 2 protocol. Visit 7) Repeat Day 3 protocol.

The total duration of time spent for each participant will be approximately 12 hours.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Individuals with fibrotic ILD (all sub-groups of ILD) who have normal oxygen saturation at rest (SpO2 > 90%) but develop exertional hypoxemia as demonstrated by a SpO2 = 80-89% with activity (measured during 6MWT).
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Exclusion Criteria
  • Use of home oxygen therapy within the previous year for the management of ILD, co-morbid conditions that may require oxygen therapy (such as COPD, cardiovascular disease, or other illnesses), or individuals that require the use of non-invasive ventilation. Additionally, individuals with significant cardiovascular, metabolic, neuromuscular or any other disease that could contribute to dyspnea or abnormal cardiopulmonary responses to exercise will be excluded. Individuals with musculoskeletal injuries that prevent them from completing cycle ergometry exercise trials and ambulation will also be excluded. Individuals with peripheral vascular disease will be excluded from measurement of vascular function (flow mediated dilation).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2 - Exertional OxygenExertional Oxygen8 weeks of portable oxygen use (from a concentrator) during exertion
Arm 3 - Exertional Oxygen + SupportExertional Oxygen8 weeks of portable oxygen use (from a concentrator) during exertion, plus additional phone calls with a respiratory educator and educational material
Arm 3 - Exertional Oxygen + SupportEducation and Support8 weeks of portable oxygen use (from a concentrator) during exertion, plus additional phone calls with a respiratory educator and educational material
Primary Outcome Measures
NameTimeMethod
Exercise toleranceBefore and immediately after the intervention

6 minute walk distance

Health Related Quality of Life, (EuroQol-5 Dimension-5 Level; EQ-5D-5L)Before and immediately after the intervention

Questionnaire for Health-Related Quality of Life. Possible Range = 5-25; 5 = 11111 (no problems on any dimension); 25 = 55555 (extreme problems on all dimensions)

Feasibility of investigation2 years

Number of patients recruited and completing the protocol in each arm

Health Related Quality of Life, (King's Brief Interstitial Lung Disease Questionnaire; KBILD)Before and immediately after the intervention

Health status questionnaire. Domain and total score ranges are 0-100; 100 represents best health status

Secondary Outcome Measures
NameTimeMethod
Dyspnea (Dyspnea-12 Questionnaire)Before and immediately after the intervention

Range from 0-36, 0 represents no breathlessness and 36 represents maximal severity

Vascular functionBefore and immediately after the intervention

Flow-mediated dilation

Cough (Leicester cough questionnaire; LCQ)Before and immediately after the intervention

Quality of life measure of chronic cough. Range from 3-21, lower score indicating greater impairment of health status due to chronic cough

Pulmonary Artery PressureBefore and immediately after the intervention

Echocardiography-derived pulmonary artery systolic pressure

Cardiac OutputBefore and immediately after the intervention

Assessed by echocardiography (L/min)

Systemic InflammationBefore and immediately after the intervention

C-Reactive Protein (CRP, venous blood, mg/L)

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