Clinical trial NCT02019641: The NIH Exercise Therapy for Advanced Lung Disease Trials: Response and Adaptation to Aerobic Exercise in Patients With Interstitial Lung Disease
Official title: The NIH Exercise Therapy for Advanced Lung Disease Trials: Response and Adaptation to Aerobic Exercise in Patients With Interstitial Lung Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Interstitial Lung Disease
Idiopathic Pulmonary Fibrosis
Interstitial Pneumonitis
Desquamative Interstitial Pneumonia
Keywords: Exercise
Interstitial Lung Disease
Pulmonary Rehabilitation
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: Inova Fairfax Hospital
First posted: 2013-12-24
Enrollment: 46
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: * 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

Primary outcomes:
measure: Change in 6-minute Walk Test Distance (6MWD)
timeFrame: Before and after 10 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
city: Falls Church
country: United States
facility: INOVA Fairfax Hospital
state: Virginia
Study officials:
affiliation: National Institutes of Health Clinical Center (CC)
name: Leighton Chan, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chan L, Chin LMK, Kennedy M, Woolstenhulme JG, Nathan SD, Weinstein AA, Connors G, Weir NA, Drinkard B, Lamberti J, Keyser RE. Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension. Chest. 2013 Feb 1;143(2):333-343. doi: 10.1378/chest.12-0993.
citation: Keyser RE, Woolstenhulme JG, Chin LM, Nathan SD, Weir NA, Connors G, Drinkard B, Lamberti J, Chan L. Cardiorespiratory function before and after aerobic exercise training in patients with interstitial lung disease. J Cardiopulm Rehabil Prev. 2015 Jan-Feb;35(1):47-55. doi: 10.1097/HCR.0000000000000083.
citation: Keyser RE, Christensen EJ, Chin LM, Woolstenhulme JG, Drinkard B, Quinn A, Connors G, Weir NA, Nathan SD, Chan LE. Changes in fatigability following intense aerobic exercise training in patients with interstitial lung disease. Respir Med. 2015 Apr;109(4):517-25. doi: 10.1016/j.rmed.2015.01.021. Epub 2015 Feb 7.
citation: Weinstein AA, Chin LM, Keyser RE, Kennedy M, Nathan SD, Woolstenhulme JG, Connors G, Chan L. Effect of aerobic exercise training on fatigue and physical activity in patients with pulmonary arterial hypertension. Respir Med. 2013 May;107(5):778-84. doi: 10.1016/j.rmed.2013.02.006. Epub 2013 Mar 7.
citation: Morris ZV, Chin LMK, Chan L, Guccione AA, Ahmad A, Keyser RE. Cardiopulmonary exercise test indices of respiratory buffering before and after aerobic exercise training in women with pulmonary hypertension: Differentiation by magnitudes of change in six-minute walk test performance. Respir Med. 2020 Apr;164:105900. doi: 10.1016/j.rmed.2020.105900. Epub 2020 Feb 25.