The NIH Exercise Therapy for Advanced Lung Disease Trials: Response and Adaptation to Aerobic Exercise in Patients With Interstitial Lung Disease

Study Overview
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Brief Summary
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Interstitial lung disease (ILD) is the result of over 200 etiological pathways arising from several different insults to the lung parenchyma: inhaled substances, drug side effects, connective tissue disease, infection, and malignancy. The disease can also be of idiopathic origin. If prolonged, the resulting inflammation causes permanent and progressive fibrotic reorganization of the parenchyma and small airways, which reduces the distensibility of the lung and impedes O2 and carbon dioxide (CO2) exchange. This study is a randomized controlled trial to determine the safety and efficacy of aerobic exercise for patients who have interstitial lung disease (ILD) uncomplicated by pulmonary hypertension. In an uncontrolled study, we observed more efficient cardiorespiratory function, increased physical work capacity, and improved health-related quality of life following aerobic exercise in this study population. Serious adverse events resulting from aerobic exercise training were not observed and our work to date has established plausibility for the efficacy of aerobic exercise training and its safety for patients with ILD.

Detailed Description
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There are two primary treatment conditions. Patients with ILD are be randomized to either an intervention consisting of aerobic exercise training plus patient education or a control condition that includes patient education only. Aerobic exercise training will consist of a 10-week regimen of supervised treadmill walking three times a week. The duration of the exercise sessions will progress from 30 minutes to 45 minutes per session over the 10 weeks, as tolerated. The intensity of the exercise will be determined based on results of a cardiopulmonary exercise test. Those randomized to control will not initially engage in aerobic exercise training. There will, however, be a secondary study: a crossover design in which subjects in the control group will complete the aerobic exercise regimen. Participants must be between the ages of 21 and 80 and live within a reasonable travel distance from the greater Washington D.C. area All pre and post testing will be conducted at the NIH Clinical Center in Bethesda, Maryland. Each testing session will last about 6 hours and will consist of a medical history and examination; six questionnaires on health, fatigue, activity, and mood; electrocardiogram, transthoracic echocardiogram, pulmonary function tests, six-minute walk test (6MWT); and urine pregnancy test (if applicable). Other required tests are: A maximum treadmill test: The exercise begins at an easy level and gradually increases until the participant says he or she can no longer continue or the investigator decides it is not safe to continue. Participants are fitted with a mask, electrodes and light sensors to measure how well the heart is working and how well the muscles use oxygen. An arterial occlusion muscle oxygenation capacity test:: During seated rest, a light sensor that measures the oxygen level in the muscle is placed on the calf while a pressure cuff will then be placed around the thigh. The cuff is rapidly inflated and held at a high pressure for up to 10 minutes and then deflated. A blood sample for complete blood count and Nt-ProBNP (a hormone that indicates damage to heart muscle). Aerobic exercise training and education may take place at either the NIH Clinical Center in Bethesda, Maryland, or the Pulmonary Rehabilitation Program at INOVA Fairfax Hospital in Falls Church, Virginia.

Official Title
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The NIH Exercise Therapy for Advanced Lung Disease Trials: Response and Adaptation to Aerobic Exercise in Patients With Interstitial Lung Disease

Conditions
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Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis, Interstitial Pneumonitis, Desquamative Interstitial Pneumonia

Intervention / Treatment
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* Other: Aerobic Exercise Training (AET)
* Other: Education


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: A diagnosis of interstitial lung disease, including idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonitis (NSIP), sarcoidosis, or other form of chronic lung fibrosis based on clinical context via clinic note from a pulmonologist. Individuals with ILD referred for pulmonary rehabilitation who are 21-80 years of age and live in the Washington metropolitan area. No episodes of fainting or significant chest pain for at least one month. No prior pulmonary rehabilitation received within the last 6 months and not currently in a maintenance program. Physically inactive (no participation in a structured exercise program as defined as more than 30 minutes of exercise 3 or more days a week within the last 6 months). EXCLUSION CRITERIA: Other medical conditions that would impair aerobic capacity or the ability to engage in physical activity, including other pulmonary, cardiovascular, neurological, musculoskeletal or metabolic conditions Other medical conditions that may pose a risk to exercise testing or training as determined by the investigators (for example, peripheral vascular disease) Diagnosis of pulmonary hypertension Inability to maintain a resting oxygen saturation greater than or equal to 90% SpO2, measured by pulse oximetry on supplemental oxygen Inability to complete a treadmill cardiopulmonary exercise test. Significant hepatic or renal dysfunction. Metastatic cancer with a life expectancy of less than one year. Active substance abuse. Severe psychiatric disease Antiretroviral therapy Pregnancy Ongoing tobacco use Acceptance onto a lung transplant waiting list Active participation in ILD drug trials Inability to read English

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic Exercise Intervention (AET+)<br>Participant with interstitial lung disease performed aerobic exercise three times a week plus weekly education for 10 weeks | Other: Aerobic Exercise Training (AET)<br>* walking on a treadmill at vigorous intensity for up to 45 minutes<br>Other: Education<br>* Weekly education<br>|
| Active Comparator: Control Group (CON)<br>Participant with interstitial lung disease performed weekly education for 10 weeks, then crossed over to perform aerobic exercise three times a week for 10 weeks | Other: Education<br>* Weekly education<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6-minute Walk Test Distance (6MWD) | The 6-minute walk test (6MWT) is a measure of physical capacity and subjects are instructed to walk as far as possible around a pre-measured walking course over a time period of six minutes. The 6-minute walk test distance (6MWD) is the total distance walked in meters during the 6MWT and greater distance walked means better physical capacity. This outcome is reported as the difference between time-points (post- minus pre-10 weeks). | Before and after 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Interstitial Lung Disease, Pulmonary Rehabilitation