The Acute Effect of Aerobic Exercise on Sleep in Patients With Depression

Depression Clinical Trial

— EASED  

Official title:

The Acute Effect of Aerobic Exercise on Sleep in Patients With Depression: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03673397
• Other study ID #: EASED-trial
• Status: Completed
• Phase: N/A
• Start date: September 24, 2018
• Est. completion date: January 6, 2020

Study information

• Verified date: February 2020
• Source: Oberwaid AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this trial is to investigate the effects of a single bout of aerobic exercise on sleep in patients with depression.

Description:

PRIMARY OBJECTIVE:

The primary objective of this study is to evaluate whether a single bout of aerobic exercise improves sleep efficiency more than a control condition in patients with depression.

SECONDARY OBJECTIVES:

Secondary objectives are to assess the effects of a single bout of aerobic exercise on 1) sleep continuity, 2) sleep architecture, 3) pre-sleep arousal, 4) subjective sleep quality, 5) daytime sleepiness, 6) nocturnal blood pressure, 7) heart rate variability, and 8) the frequency and severity of adverse events.

DESIGN:

This will be a two-arm parallel group, randomized, outcome assessor blinded, controlled, superiority trial. According to sample size calculation a total of 92 patients will be randomized using minimization. The trial will take place in the first five days of the patients' psychosomatic in-patient rehabilitation in the clinic OBERWAID, St.Gallen, Switzerland. The study visits are scheduled is as follows:

Day 0-2: Screening, inclusion, and graded exercise test to determine exercise intensity of intervention

Day 3: Questionnaires for background information

Night 1 (day 3-4): Baseline polysomnography and sleep related questionnaires

Day 4: Randomized allocation (control or exercise condition) and performing corresponding intervention

Night 2 (day 4-5): Follow-up polysomnography and sleep related questionnaires

Day 5: Daytime sleepiness questionnaire

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: January 6, 2020
• Est. primary completion date: January 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Inpatient psychosomatic rehabilitation in the clinic OBERWAID, St.Gallen, Switzerland

• Age: =18 and =65 years old

• Primary diagnosis of depression (F32, F33) without psychotic episode according to International Statistical Classification of Diseases, 10th edition

Exclusion Criteria:

• Regular use of hypnotic agents (patients were included if no hypnotic agents were taken 2 weeks prior to study participation)

• Factors precluding exercise testing or training

• Use of beta-blockers (with the exception of Carvedilol & Nebivolol)

• Use of opioids

• History of epilepsy

• Restless legs syndrome defined by =7 points on the restless legs syndrome screening questionnaire (RLSSQ)

• Moderate or severe sleep apnea defined by an oxygen desaturation index (ODI) =15 in the first polysomnography.

• Morbid adiposity with BMI >40

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Disease
• Dyssomnias
• Insomnia
• Insomnia Due to Other Mental Disorder
• Insomnia Related to Another Mental Condition
• Insomnia, Psychophysiological
• Mental Disorders
• Parasomnias
• Sleep
• Sleep Deprivation
• Sleep Disorder
• Sleep Disturbance
• Sleep Fragmentation
• Sleep Initiation and Maintenance Disorders
• Sleep Wake Disorders

Intervention

Behavioral:
• Aerobic exercise, bicycle ergometer
Exercise performed below individual anaerobic threshold for 30 minutes

Locations

Country	Name	City	State
Switzerland	Oberwaid Ag	St.Gallen

Sponsors (4)

Lead Sponsor	Collaborator
Oberwaid AG	Institute for Exercise and Health Sciences, University of Basle, Switzerland, University of Basel, University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mood assessed by self-rating questionnaire 'Befindlichkeitsskala' (BFS)	Eight subscales are calculated from the 'Befindlichkeitsskala' (BFS): activity, elation, contemplation, calmness, fatigue, depression, anger, and excitement. Values of all subscale range from 1 to 5. Higher scores on the subscale depression indicate worse outcome. Higher scores on the other subscales cannot a priori be judged as representing better or worse outcomes.	Immediately before and at the end of the control condition as well as the exercise intervention.
Primary	Change from baseline in sleep efficiency (%) at follow-up assessed by polysomnography	Calculated as (total sleep time / total recording time) * 100. Higher values represent a better outcome. A one-way ANCOVA will be computed with baseline sleep efficiency (%) and minimization factors as covariates, intervention as the independent variable, and follow-up sleep efficiency (%) as the dependent variable.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in wake after sleep onset (minutes) at follow-up assessed by polysomnography	Calculated as time awake after first sleep episode. Lower values represent better outcome. A one-way ANCOVA will be computed with baseline wake after sleep onset and minimization factors as covariates, intervention as the independent variable, and follow-up wake after sleep onset as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in sleep onset latency (minutes) at follow-up assessed by polysomnography	Calculated as time between lights-off marker and first epoch of any sleep stage. Lower values represent better outcome. A one-way ANCOVA will be computed with baseline sleep onset latency and minimization factors as covariates, intervention as the independent variable, and follow-up sleep onset latency as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in number of awakenings at follow-up assessed by polysomnography	Calculated as number of wake periods of at least two epochs after sleep onset. Lower values represent better outcome. A one-way ANCOVA will be computed with baseline number of awakenings and minimization factors as covariates, intervention as the independent variable, and follow-up number of awakenings as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in stage 1 sleep (% of total sleep time and minutes) at follow-up assessed by polysomnography	Calculated as Stage 1 sleep (in minutes and % of total sleep time). A one-way ANCOVA will be computed with baseline stage 1 sleep (% of total sleep time and minutes) and minimization factors as covariates, intervention as the independent variable, and follow-up stage 1 sleep (% of total sleep time and minutes) as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in stage 2 sleep (% of total sleep time and minutes) at follow-up assessed by polysomnography	Calculated as Stage 2 sleep (in minutes and % of total sleep time). A one-way ANCOVA will be computed with baseline stage 2 sleep (% of total sleep time and minutes) and minimization factors as covariates, intervention as the independent variable, and follow-up stage 2 sleep (% of total sleep time and minutes) as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in stage 3 sleep (% of total sleep time and minutes) at follow-up assessed by polysomnography	Calculated as Stage 3 sleep (in minutes and % of total sleep time). A one-way ANCOVA will be computed with baseline stage 3 sleep (% of total sleep time and minutes) and minimization factors as covariates, intervention as the independent variable, and follow-up stage 3 sleep (% of total sleep time and minutes) as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in rapid eye movement sleep (% of total sleep time and minutes) at follow-up assessed by polysomnography	Calculated as rapid eye movement sleep (in minutes and % of total sleep time). A one-way ANCOVA will be computed with baseline rapid eye movement sleep (% of total sleep time and minutes) and minimization factors as covariates, intervention as the independent variable, and follow-up rapid eye movement sleep (% of total sleep time and minutes) as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in light sleep (% of total sleep time and minutes) at follow-up assessed by polysomnography	Calculated as sum of Stage 1 & 2 sleep (in minutes and % of total sleep time). A one-way ANCOVA will be computed with baseline light sleep (% of total sleep time and minutes) and minimization factors as covariates, intervention as the independent variable, and follow-up light sleep (% of total sleep time and minutes) as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in non-rapid eye movement sleep (% of total sleep time and minutes) at follow-up assessed by polysomnography	Calculated as sum of Stage 1, 2 and 3 sleep (in minutes and % of total sleep time). A one-way ANCOVA will be computed with baseline non-rapid eye movement sleep (in minutes and % of total sleep time) and minimization factors as covariates, intervention as the independent variable, and follow-up non-rapid eye movement sleep (in minutes and % of total sleep time) as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in rapid eye movement sleep-latency (minutes) at follow-up assessed by polysomnography	Calculated as time between sleep onset and the occurrence of the first REM sleep epoch (minutes). A one-way ANCOVA will be computed with baseline rapid eye movement sleep-latency (minutes) and minimization factors as covariates, intervention as the independent variable, and follow-up rapid eye movement sleep-latency (minutes) as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in stage shift index at follow-up assessed by polysomnography	Calculated as the number of transitions between any wake or sleep stage divided by hours of total sleep time. Lower values represent better outcome. A one-way ANCOVA will be computed with baseline stage shift index and minimization factors as covariates, intervention as the independent variable, and follow-up stage shift index as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in subjective sleep quality at follow-up assessed by self-rated questionnaire 'revised Schlaffragebogen A'	Five factors are calculated from 'revised Schlaffragebogen A': sleep quality, recuperation after sleep, calmness prior to sleep, exhaustion prior to sleep, and psychosomatic symptoms during sleep. Values range from 1 to 5. Higher values indicate better outcome in the first three subscales. Lower values indicate better outcome in the last two subscales. A one-way ANCOVA will be computed with baseline values and minimization factors as covariates, intervention as the independent variable, and follow-up value as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in subjective pre-sleep arousal at follow-up assessed by self-rated questionnaire 'Pre-Sleep Arousal Scale'	Two factors are calculated from 'Pre-Sleep Arousal Scale': cognitive arousal (range: 7-35) and somatic arousal (range: 8-40). Lower values indicate better outcome in both scales. A one-way ANCOVA will be computed with baseline values and minimization factors as covariates, intervention as the independent variable, and follow-up value as dependent variables.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in pre-sleep autonomic modulation at follow-up	Assessed through short-term (5 minutes as of lights off) heart rate variability measured by ECG (modified lead II). Heart rate variability will be assessed by time-domain (Root Mean Square of successive differences of normal-to-normal intervals (RMSSD) and standard deviation of normal-to-normal intervals (SDNN)) as well as frequency domain (total power (TP), low frequency power (LF), high frequency power (HF), and ratio of LF-to-HF power (LF/HF)). A one-way ANCOVA will be computed with baseline heart rate variability indices and minimization factors as covariates, intervention as the independent variable, and follow-up heart rate variability indices as the dependent variable.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in nocturnal autonomic modulation at follow up	Assessed by heart rate variability through a 6-hour period as of sleep onset, measured by ECG (modified lead II). Heart rate variability will be assessed by time-domain (Root Mean Square of successive differences of normal-to-normal intervals (RMSSD) and standard deviation of normal-to-normal intervals (SDNN)) as well as frequency domain (total power (TP), low frequency power (LF), high frequency power (HF), and ratio of LF-to-HF power (LF/HF)). The 6-hour period is split into six hourly segments for analysis. Hourly segments of nocturnal HRV will be analyzed using a linear mixed model with subject as random effect, adjusting for baseline and minimization factors.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in post-sleep autonomic modulation at follow-up	Assessed through short-term (5 minutes as of last awakening) heart rate variability measured by ECG (modified lead II). Heart rate variability will be assessed by time-domain (Root Mean Square of successive differences of normal-to-normal intervals (RMSSD) and standard deviation of normal-to-normal intervals (SDNN)) as well as frequency domain (total power (TP), low frequency power (LF), high frequency power (HF), and ratio of LF-to-HF power (LF/HF)). A one-way ANCOVA will be computed with baseline heart rate variability indices and minimization factors as covariates, intervention as the independent variable, and follow-up heart rate variability indices as the dependent variable.	Baseline (night 1) and follow-up (night 2)
Secondary	Change from baseline in nocturnal mean arterial pressure at follow-up assessed by pulse transit time (ECG, modified lead II; fingertip photoplethysmogram, single initial calibration measurement)	Mean arterial pressure is calculated from systolic and diastolic blood pressures as follows: [(0.33 * systolic pressure) + (0.66 * diastolic pressure)]. Mean arterial pressure will be reported separately for total sleep time, non-rapid eye movement sleep, and rapid eye movement sleep. A one-way ANCOVA will be computed with baseline mean arterial pressure and minimization factors as covariates, intervention as the independent variable, and follow-up mean arterial pressure as the dependent variable.	Baseline (night 1) and follow-up (night 2)
Secondary	State sleepiness assessed by self-rated questionnaire 'Stanford Sleepiness Scale' (SSS)	This is a single item questionnaire on a 7-point scale (1-7). Higher values indicate worse outcome.	Day 5 (i.e. day after night 2): at 08:00 am, 12 noon, 04:00 pm, and 08:00 pm
Secondary	Difference in adverse events between exercise and control group	Adverse events will be explicitly assessed through a questionnaire. Patients will be asked whether they experienced adverse effects on a five point Likert scale (not at all, very) using the following categories: Pain (if yes, location), dizziness, cardiovascular symptoms (e.g. angina symptoms, cyanosis, pallor), respiratory symptoms (e.g. wheezing), nausea, falls (yes or no), other (to be described).	Immediately after termination of exercise intervention or control condition and after awakening from follow-up (night 2)