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

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Baseline (night 1) and follow-up (night 2)

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.

Time frame: Day 5 (i.e. day after night 2): at 08:00 am, 12 noon, 04:00 pm, and 08:00 pm

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).

Time frame: Immediately after termination of exercise intervention or control condition and after awakening from follow-up (night 2)