Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT03800017 |
| Other study ID # |
H18-02059 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2024 |
| Est. completion date |
December 31, 2026 |
Study information
| Verified date |
May 2024 |
| Source |
University of British Columbia |
| Contact |
Olivia Ferguson, MSc |
| Phone |
1-604-806-8835 |
| Email |
Olivia.Ferguson[@]hli.ubc.ca |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Dyspnea (i.e. breathlessness) and exercise intolerance are common symptoms for patients with
interstitial lung disease (ILD), yet it is not known why. It has been suggested that muscle
dysfunction may contribute to dyspnea and exercise intolerance in ILD. Our study aims to: i)
examine differences in the structure and function of the leg muscles in ILD patients, ii)
determine if leg muscle fatigue contributes to dyspnea and exercise limitation in patients
with ILD, and iii) determine the effects of breathing extra oxygen on leg muscle fatigue, as
well as ability to exercise in ILD patients.
Description:
PURPOSE:
The primary purpose of the proposed work is to characterize skeletal muscle function in
patients with interstitial lung disease (ILD), and to determine the physiological and sensory
consequences of impaired skeletal muscle function in ILD during exercise.
HYPOTHESES:
The hypotheses are threefold; i) patients with ILD will have impaired skeletal muscle
function when compared to healthy controls, ii) impairments in skeletal muscle function
predispose ILD patients to exercise-induced quadriceps muscle fatigue, increase the
perception of exertional dyspnea, as well as reduce exercise tolerance, and iii) delivery of
supplemental oxygen during exercise mitigates exercise-induced quadriceps muscle fatigue,
attenuates the perceived intensity of dyspnea, and improves exercise tolerance.
OBJECTIVE:
The objective of the proposed study is to comprehensively investigate skeletal muscle
dysfunction in patients with ILD and characterize its impact on dyspnea and exercise
tolerance. In doing so, the proposed work will be the first to comprehensively assess
skeletal muscle function in patients with ILD as well as determine its functional
consequences. The results will provide important insight into the putative role of skeletal
muscle dysfunction on exercise limitation in patient with ILD.
JUSTIFICATION:
ILD refers to a diverse group of diseases that share common physiological characteristics
resulting from inflammation and/or fibrosis of the lung parenchyma. ILD has an estimated
prevalence of approximately 67-81 cases per 100 000 individuals. Given the heterogeneity of
disease sub-types, it is difficult to determine a precise median survival for patients with
ILD, however; in patients with idiopathic pulmonary fibrosis, the most common ILD sub-type,
have a median survival of only 2-3 years from the time of diagnosis. For patients with ILD,
dyspnea (i.e. breathlessness) is the most common symptom. Dyspnea can be extremely
debilitating, particularly during physical exertion. The clinical significance of dyspnea in
ILD is underscored by its strong correlation with quality of life and mortality. Patients
attempt to minimize dyspnea by avoiding physical activity, resulting in deconditioning and an
associated reduction in functional capacity. The importance of maintaining functional
capacity is highlighted by the fact that ILD patients with the lowest physical activity
levels have the lowest quality of life and the highest mortality. The effective management of
dyspnea and exercise intolerance is therefore of critical importance when considering the
management of patients with ILD.
The pathophysiological mechanisms of dyspnea and exercise intolerance in ILD are complex,
multifactorial, and poorly understood. Indeed, relatively few studies that have adequately
investigated the mechanistic basis of dyspnea and exercise intolerance in patients with ILD.
It is generally agreed upon that exercise limitation in ILD is related to the combination of
altered respiratory mechanics, gas exchange impairment, and circulatory limitation. However,
it is assumed that dyspnea and exercise intolerance are exclusively related to the
respiratory and circulatory impairment associated with the pathogenesis of ILD. While this
assumption is reasonable, it ignores the potentially crucial role of skeletal muscle
dysfunction as a source of dyspnea and exercise intolerance. Recent experimental evidence
indicates that skeletal muscle dysfunction contributes to both dyspnea and exercise
intolerance in COPD.
A growing body of literature supports the notion that skeletal muscle dysfunction is common
in ILD. While the precise mechanisms remain unclear, several well-established skeletal muscle
dysfunction-promoting factors are present in many ILD patients, including: chronic
hypoxaemia, oxidative stress, pulmonary and systemic inflammation, physical deconditioning,
malnutrition, and corticosteroid use. These factors may act individually or synergistically
to impair skeletal muscle function by causing muscle atrophy, mitochondrial dysfunction, a
reduction in type I muscle fibre proportion, and increases in intramuscular fat. To our
knowledge, there is limited imaging data of skeletal muscle morphology in ILD, and
assessments of skeletal muscle oxidative capacity, and contractile function have not been
concurrently obtained. If present, skeletal muscle dysfunction likely reduces locomotor
muscle oxidative capacity, leading to premature fatigue, increased dyspnea, and diminished
exercise tolerance. Most importantly, there is no data on the physiological effects of
skeletal muscle fatigue and dysfunction on dyspnea and exercise capacity nor whether targeted
treatment options such as supplemental oxygen (O2) delivery can attenuate muscle fatigue.
Accordingly, the aims of the proposed research are threefold: i) to characterize skeletal
muscle function in patients with ILD compared to healthy controls, ii) to determine the
influence of skeletal muscle dysfunction on dyspnea, fatigue, and exercise intolerance in
patients with ILD compared to healthy controls, and iii) to determine if improving exercise
tolerance using supplemental oxygen relieves exercise-induce skeletal muscle fatigue in ILD
patients.
RESEARCH DESIGN:
Experimental hypotheses tested using combination of research designs. To test the hypotheses
i) and ii), the investigators will use a cross sectional design. To test hypothesis iii), the
investigators will use a single-blind placebo-controlled study design.
METHODS Participants will report to the laboratory on four separate occasions separated by a
minimum of 48 hours, and each visit will last ~2-3 hours.
Visit 1:
Participants will complete medical history screening, complete a series of questionnaires
concerning chronic activity-related dyspnea, quality of life, and physical activity.
Participants will then have their height and weight measured and perform pulmonary function
testing. Finally, participants will perform a symptom limited incremental cycle exercise
test. Detailed physiological and sensory measurements will be obtained immediately before and
throughout the incremental cycle exercise test.
Visit 1 will be intended to characterize participant's pulmonary function and exercise
capacity.
Visit 2:
Participants will undergo a magnetic resonance imaging scan to assess the volume and the fat
percentage of their quadriceps muscles They will then perform a series of tests aimed at
evaluating their quadriceps muscle function, including: i) assessment of maximum voluntary
quadriceps muscles strength, and ii) the non-invasive assessment of the oxidative capacity of
their quadriceps muscle using near-infrared spectroscopy.
Data from visit 2 will be used to address hypothesis 1 by characterizing participant's
quadriceps muscle function.
Visits 3:
Participants will perform a constant-load exercise test to exhaustion while breathing ambient
air (i.e., 20.93% oxygen). The work load will be set at 75% of the highest work rate achieved
during the incremental exercise test performed during visit 1.
Data from visits 3 and 4 will be used to address hypothesis 2 by characterizing the effect of
exercise on skeletal muscle fatigue in patients with ILD and healthy controls.
Visit 4:
Participants will perform a constant-load exercise test while breathing supplemental oxygen
(i.e., 60% oxygen). The work load will be set at 75% of the highest work rate achieved during
the incremental exercise test performed during visit 1 and the test will be terminated once
participants reach the same time that they achieved during the constant-load exercise test on
Day 3.
Data from visit 4 will be used to address hypothesis 3 by determining if supplemental oxygen
can be used to alleviate exercise-induced skeletal muscle fatigue in patients with ILD and
healthy controls.
