Clinical trial NCT04997200: Effect of Sleep Deprivation on Breathlessness and Exercise Capacity in COPD
Official title: Effect of Sleep Deprivation on Breathlessness and Exercise Capacity in COPD: a Randomized Crossover Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COPD
Keywords: Dyspnea
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Lead sponsor: Skane University Hospital
Sponsor class: OTHER
Collaborators: name: Blekinge County Council Hospital
First posted: 2021-08-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Performed in randomized order on two separate days, at least seven days apart and no more than six weeks apart.

* Intervention: A night without sleep. No daytime sleeping the day before the test. Participants are observed by staff at the trial unit during the night before the test.
* Control: Normal night's sleep (at least six hours of sleep) in the patient's home.

The participants wear an actigraph during 48 hours before the test to ensure adherence to the allocated condition (sleep deprivation or control).
Primary purpose: BASIC_SCIENCE

Brief summary: This is a randomized controlled cross-over trial designed to measure the effect of one night's sleep deprivation on exercise endurance, ventilation and breathlessness in outpatients with COPD.

Detailed description: Background:

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in the world. Breathlessness and exercise limitation are cardinal symptoms in COPD with grave consequences for the patient. Even with optimal COPD treatment a large number of these patients experience a breathlessness which limits their everyday life. Physical activity is the main trigger of breathlessness in daily life, but knowledge is limited on how other factors may affect exercise performance, breathing and exertional breathlessness in patients with COPD.

Sleep deprivation is common in the population in patients with COPD, and especially in patients with worsening health status and during hospitalizations. As many as 40-45% of patients older than 70 experience sleep deprivation during hospitalization. As many as 21 % of patients with COPD have a disturbed sleep. A recent study on healthy young males who breathed against an inspiratory resistance showed that one night's sleep deprivation significantly reduced their respiratory endurance and induced worse and more disturbing breathlessness.

Little is known how sleep loss affects patients with COPD in an outpatient setting. Several studies have evaluated the effect of sleep deprivation on exercise capacity in young healthy adults. However, very few studies have examined the effect of sleep deprivation on the exercise capacity or exertional breathlessness in patients with COPD; most data pertain to observational studies where no intervention took place and data from a randomized controlled trial (RCT) is needed. The presence of disturbed sleep in patients with COPD - and especially in relation to worsenings and hospitalizations, could have a marked detrimental effect on their breathing, increase suffering from distressing breathlessness and potentially increase the risk of adverse health outcomes and worse prognosis. Directed actions to improve sleeping in these settings could in that case improve the patients' outcomes.

Aim:

To test the effect of one sleepless night on breathlessness, exercise endurance and ventilation in patients with COPD.

Method:

This is a randomized (ratio 1:1), controlled, crossover trial of the effect of one night's sleep deprivation vs. normal sleep on exercise endurance, ventilation and breathlessness in outpatients with COPD. The study will not be blinded for participants and staff (due to the nature of the intervention) but will be blinded for the analyst.

The intervention is one night without sleep, and the control is one night with normal sleep. The test is a bicycle test (exercise test on a bike with continuous analysis of ventilation and gaseous exchange) carried out as a sub-max test at 75% of maximum capacity until the test person cannot go on.

The study consists of three visits. At the first visit, informed consent is collected, and inclusion and exclusion criteria are evaluated. Also, information is collected regarding the person's COPD-diagnosis, medication, and other illnesses. Specific surveys are Pittsburgh Sleep Quality Index (PSQI), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) scale, 7-point Global Impression of Change (GIC) scale, Experienced sleep quality (Likert scale), Multidimensional Dyspnea Profile (MDP) to assess the person's sleep and respiration. Baseline values for dynamic spirometry, saturation, and blood pressure are also measured during the first visit. Afterwards, a bicycle test is carried out according to normal clinical standards. This involves increasing the resistance (in Watts) according to a set protocol until the test person is unable to continue. This takes roughly 6-10 minutes and provides a maximum performance value for the individual. This maximum value is used for visit number two and three. After this first visit the order of the sleepless night is randomized for either visit two or three.

At the second and third visit spirometry, saturation and blood pressure are once more measured. The person is evaluated for contraindications. Then a new bicycle test is carried out at 75% of the maximum W achieved at the first visit. The test takes around 10 minutes, and continues until the person is unable to continue. During this test, ventilation is measured as respiratory rate (RR), minute ventilation (MV), oxygen consumption (VO2), carbon dioxide consumption (VCO2), the respiratory quotient (VCO2/VO2), inspiratory capacity manoeuvre (IC), dynamic hyperinflation, ventilatory reserve capacity, ventilation efficiency (MV/VCO2-curve) and the anaerobic threshold. During the test the person is also assessed for how difficult the breathing feels (0-19 Borg CR10), how tired the legs feels (Borg CR10), how uncomfortable the breathing feels (mBorg 0-10) every two minutes and at the end of the test. At the end of the test the test person is asked about the reason for ending the test, how the breathing was experienced (Multidimensional Dyspnea Profile, MDP), and how motivated they were to carry out the test (0-10 NRS). The person is also monitored with EKG during the test, and the blood pressure is measured every two minutes. The results are then compared between the test where the person had a normal night's sleep, and the test where the person was awake the whole night before.

The normal night's sleep is assessed using some simple questions, such as: "How did you sleep tonight" and "How satisfied are you with the night's sleep?". It is also evaluated using an Actigraph bracelet that measures movement when worn. The bracelet is worn for 48 hours preceding both tests.

The night when the person is going to be awake is spent at the test lab, after eating a normal dinner at home. They then spend an entire night in a room where they can watch TV, use a phone or tablet or read books and magazines. They will be monitored by staff to help them stay awake during the night. They cannot eat, drink or smoke anything not usually consumed during the night (other than water). They then eat a normal breakfast of their choosing, and the test is carried out just like the one where they slept normally.

Eligibility criteria: Inclusion Criteria: (All required)

* Age 18 years or older
* COPD diagnosed by physician in accordance with Global Initiative For Chronic Obstructive Lung Disease (GOLD) guidelines (GOLD 2021), with a spirometric ratio of the forced expired volume in one second (FEV1) / forced vital capacity (FVC) \< 0.7 and a FEV1 \< 80% of predicted post bronchodilator at baseline.
* Self-reported average sleep time of six hours or longer during a normal night.
* No regular treatment with sleep medication or anxiolytics.
* Able to cycle
* Able to talk and write Swedish well enough to participate in the study procedures, as judged by the Investigator.

Exclusion Criteria:

* Resting peripheral oxygen saturation (SpO2) \< 92%
* Night shift worker
* Hospitalization or clinical instability during the last four weeks
* Treatment with supplementary oxygen at rest or during exercise
* Sleep disturbance, defined as a Pittsburgh Sleep Quality Index \>5 at baseline
* Contraindication to exercise testing in accordance with clinical practice guidelines (ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003; 167:211-277)
* Expected survival shorter than six months as judged by the Investigator.

Primary outcomes:
measure: Change in breathlessness intensity (Borg CR10) between control and intervention at iso-time
timeFrame: Measured during post-control and post-intervention exercise tests, spaced 7 days to 6 weeks apart
Secondary outcomes:
measure: Change in breathlessness unpleasantness (Borg CR10) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in time to the limit of tolerance (tLIM) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in oxygen consumption between control and intervention (absolute)
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in oxygen consumption between control and intervention (%pred)
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in workload (W) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in workload (%pred) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in Minute ventilation (VE) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in tidal volume (VT) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in ventilatory reserve, (MVV) - (VE) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in cardiac reserve between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in dynamic hyperinflation and inspiratory capacity (IC) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in breathing frequency between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in breathlessness intensity at peak exercise (Borg CR10) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in leg discomfort (Borg CR10) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in timing of the anaerobic threshold (AT) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in V'O2 of the anaerobic threshold (AT) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in efficacy of ventilation (VE/V'CO2-slope and ratio at the AT) between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in respiratory exchange ratio (RER), defined as V'CO2/V'O2 between control and intervention
timeFrame: Measured during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in causes for stopping the test between control and intervention
timeFrame: Evaluated during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
measure: Change in any adverse events during the control and intervention tests
timeFrame: Evaluated during post-control and post-intervention tests, spaced 7 days to 6 weeks apart
Other outcomes:
Locations:
city: Karlskrona
country: Sweden
facility: Blekinge Tekniska Högskola (BTH)
state: Blekinge
city: Karlskrona
country: Sweden
facility: Department of Clinical Physiology, Blekinge Hospital
state: Blekinge
Study officials:
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