Outcome measures
| Outcome category | Measure | Primary/Secondary | Details |
| Subjective sleep | Daily sleep diaries | Primary | Online diaries will be completed each morning (~5 min) during each 2-week assessment period and 8 weeks of treatment. Primary outcome variables include: sleep onset latency (time from initial lights-out until sleep onset), wake after sleep onset (time awake after initial sleep onset until last awakening), number of awakenings, total sleep time, sleep efficiency (total sleep time/time spent in bed ×100) and sleep quality rating (1—very poor to 5—excellent). Sleep and pain medication consumption variables will include: name, dosage and time taken. Sleep medication will be converted to number of lowest recommended dosage units,72 and pain medication to morphine equivalent dosage.73 |
| Insomnia Severity Index (ISI) | Primary | At each time point, participants will complete the ISI (primary outcome).74 The ISI is a 7-item questionnaire that assesses the frequency and/or severity of insomnia symptoms (eg, “rate the current severity of your difficulty falling asleep”; choices range from 0 (none) to very severe (5)), as well as questions regarding the impact of insomnia on daytime functioning (eg, “to what extent do you consider your sleep problem to interfere with your daily functioning”) (eg, daytime fatigue, mood, ability to function at work/daily chores, concentration, memory, mood, etc)) currently; choices range from 0 (not interfering at all) to 5 (very much interfering). Total scores on the ISI range from 0 to 28, with higher scores representing more severe insomnia. | |
| Objective sleep | Daily actigraphy | Secondary | Actiwatch 2 (Philips Respironics) is a watch-like device that monitors light and gross motor activity. Data will be analysed by proprietary software using 30 s epochs. A validated algorithm estimates the same variables (secondary outcomes) provided by diaries (except sleep quality). Participants wear the device 24/7 during each 2 weeks of assessment, and 8 weeks of treatment. |
| Polysomnographic (PSG) sleep | Secondary | The Comet-PLUS Portable (Natus Neurology) Recording System will be used to conduct a single in-home overnight sleep study at baseline, post-treatment and both follow-ups. Consistent with ambulatory recommendations,75 monitoring consists of 10 electroencephalography, 2 EOG and 3 electromyography (EMG) (chin) using standard placements. It also includes respiratory inductance plethysmography (thoracic/abdominal effort), oximeter (pulse/oxygen saturation), ECG, R/L anterior tibialis EMG, oral-nasal airflow thermocouple and nasal cannula pressure transducer. We require 4 hours of acceptable data (ie, scorable stage/respiratory events) and follow Sleep Heart Health Study76 procedures for training, data management and scoring. PSG provides sleep stage % (stage 1, 2, 3, rapid eye movement sleep) and absolute values for diary variables (secondary outcomes). | |
| Arousal | Peripheral Arousal—heart rate variability (HRV) | Primary | Using Holter monitors, we will obtain 5 min ECG recordings during rest in a quiet controlled environment at each assessment. Time and spectral analysis of the short-term variability of heart rate (HR) will be performed using Pathfinder (Spacelabs, Seattle, Washington) software to assess the neural regulation of HR. The time domain indices reflect the beat-to-beat variability with respect to time. The variables SD of the N-N intervals and the percentage of N-N intervals that exceed 50 ms will be examined. The frequency domain indices reflect the underlying rhythms of the mechanisms modulating HR. High frequency (0.15–0.4 Hz), low frequency (0.04–0.15 Hz) and very low frequency (below 0.04 Hz) spectral bands will be examined. |
| Global cognitive arousal—Perceived Stress Scale (PSS)77 | Primary | The PSS (primary outcome) is a 10-item questionnaire that asks participants to appraise their stress level during the past month in response to several everyday situations (eg, “in the last month how often have you been able to control irritations in your life?”). Choices range from 0 (never) to 4 (very often). Higher total scores on the PSS indicate worse perceived stress. | |
| Insomnia-specific cognitive-affective arousal—Dysfunctional Beliefs and Attitudes about Sleep (DBAS)* | Primary | The DBAS74 is a 30-item scale that assess the degree to which an individual agrees with statements regarding sleep (eg, ‘Medication is probably the only solution to sleepiness’, “I need 8 hours of sleep to feel refreshed and function well during the day”). Participants rate their belief in each statement from 0 (strongly disagree) to 10 (strongly agree). Scores for each item are summed and higher scores on the DBAS indicate worse cognitive affective arousal related to insomnia. | |
| Pain-specific cognitive-affective arousal-catastrophising—Pain Catastrophising Scale (PCS)78 | Primary | The PCS is a 13-item scale that measures the degree (from 0—not at all to 4—all the time) to which participants experienced certain thoughts or feelings during past painful events. Items are scored and total scores on the PCS represent worse pain catastrophising. | |
| Pain | Daily clinical pain—Electronic Daily Diaries | Primary | On the daily electronic diaries, participants provide ratings on a 0–100 scale regarding their pain intensity (0—no pain sensation, 100—most intense pain imaginable) and pain unpleasantness (0—not at all unpleasant, 100—most unpleasant imaginable). |
| Subjective pain—McGill Pain Questionnaire (MPQ)79 80 | Secondary | The MPQ assesses participants pain symptoms across 21 categories. For each category, participants select the best word that described their pain. Qualitative responses are coded by numerical value (eg, 1–3 or 1–5), with higher values representing worse pain in that category. If they do not experience a specific category of pain, they do not provide a response to that category. Category scores are summed and total scores could range from 0 (no pain) to 78 (severe pain). | |
| Patient-Centred Outcomes Questionnaire (PCOQ)81 | Secondary | The PCOQ is a 5-item questionnaire that assess on a 0-point to 10-point scale usual levels of pain, desired levels of pain, what level of improvement in treatment outcomes they would consider successful, what level of improvement in treatment outcomes they expect after treatment, importance of improvement in treatment outcomes. | |
| Pain-related disability—Pain Disability Inventory (PDI)82 83 | Secondary | The PDI includes 7-item questionnaire rated on an 11-point scale (0=no disability, 10=total disability) indicating the degree to which chronic pain interferes with participant functioning in the following areas: family/home responsibilities, recreation, social activity, occupation, sexual behaviour, self-care and life-support activity. The seven ratings are summed to compute a total score (0–70), with higher scores indicated worse pain disability. | |
| Mood | State Trait Anxiety Inventory (STAI)84 | Covariate | STAI asks respondents to rate how true 20 self-descriptive statements (eg, I feel calm) are on a 4-point scale (1=not at all, 4=very much so). Typically, respondents are asked to rate statements according to how they generally feel (trait-anxiety scale) and how they feel in the current moment (state-anxiety scale). Total scores range from 20 to 80, with higher scores indicating greater maladjustment. |
| Beck Depression Inventory-Second Edition (BDI-II)85 | Covariate | The BDI-II contains 21 items that measure the severity of depressive symptomatology on a 3-point scale (0=absence of symptoms, 3=most severe). Typically, respondents answer for the previous week, but the previous 2 weeks were used in this study to match the 2-week activity recording period for each assessment. Total scores range from 0 to 63. Ranges for clinical levels of depression are 0–13 (minimal), 14–19 (mild), 20–28 (moderate) and 29–63 (severe). | |
| Pain Anxiety Symptoms Scale (PASS-20)86 | Covariate | The PASS measures fear and anxiety responses related to pain. The PASS-20 revised short form version contains 20 items in which participants must rate the frequency in which they experience fearful and anxiety ridden responses related to pain or pain-related situations. This scale is widely used in clinical screening of chronic pain and pain research. | |
| Anxiety and Preoccupation about Sleep Questionnaire (APSQ)87 | Covariate | The APSQ measures the intensity of both daytime and nighttime worry related to insomnia. Participants are presented with 10 statements describing several sleep related worries and participants are asked to indicate how true they on a scale from 0 (not true) to 10 (very true). Scores on this scale are associated with self-reported (eg, diary) sleep measures as well as daytime impairment, with higher scores representing worse anxiety related to sleep. | |
| Neuroimaging | Neural plasticity and central sensitisation | Primary | Three imaging protocols 1) structural MRI (MPRAGE), 2) functional MRI (fMRI) (EPI blood-oxygen-level dependent) and 3) diffusion-weighted imaging (DWI), will assess neural plasticity and central sensitisation. Image acquisition. Imaging data will be acquired with Siemens’ new MAGNETOM Vida 3T and a 20-channel head-neck coil. The parameters for the 3D-T1-weighted structural scans are: 256 axial slices (0.90×0.89×0.89 mm3; TR=0.75 s, TE=0.0045 s, flip angle=750°, matrix=256×256, FOV=256 mm. T2-gradient EPI sequence for the resting state and fMRI scans will use the following parameters: whole brain, 36-contiguous slices (axial), 3 mm3 isotropic voxels, oriented parallel to the AC-PC plane, TR=2.46 s; TE=30 ms; flip angle=90°; 76×76 matrix and 120 volumes. The parameters for the diffusion-weighted scans are: 32 slices, 1×1×3.25 mm2, TR=3.6 s, TE=0.064 s, flip angle=90°, directions=6. The sequence of scan acquisition is: Localizer, gradient field map, 3D anat, resting state (x2, ~5 min), fMRI experimental pain scans (x3, ~25 min), DWI (~12 min). During the resting state scans, subjects are told to relax, limit movement and try not to fall asleep. In preparation for the experimental pain scan, participants will first undergo quantitative sensory testing (QST) calibration trials outside of the scanner, in order to determine individual pain tolerance and to ensure that experienced pain intensity is equal in both treatment groups at baseline. A computer-controlled Medoc Pain and Sensory Evaluation System (Pathway Model ATS, Medoc Advanced Medical Systems, Durham, North Carolina) will be used to deliver thermal stimuli. QST calibration uses a series of calibration trials (CTs), to identify their pain tolerance temperature, which will be used during their experimental pain scanning session. The CTs start at 43°C and increase by 1°C until their tolerance, or 51°C is reached, whichever comes first. Subjects will sit in a chair, remove their shoes and socks and extend their feet outward. A researcher will wipe the bottom of their foot with an alcohol pad, after which a contact heat thermode will be placed on the plantar surface of the foot. Each stimulus cycle is initiated by the experimenter via key press. After each stimulus, subjects will describe the sensation (pain/not painful) and rate its pain intensity on a scale from 0—no pain to 100—worst pain imaginable. Once the ratings and interstimulus interval have finished, the cycle will be repeated until their tolerance temperature is identified (ie, the lowest temperature with a pain intensity rating of ≥65). This will be the temperature that will be used during their scanning sessions. During each 5 min experimental pain scan, thermal stimuli will be delivered with an MR compatible, computer-controlled, CHEPS Pathway system, which is a peltier-element-based stimulator, and is capable of producing stimuli across a range of temperatures (33°C–51°C). The start of each scan will begin with the thermode at ambient temperature for 30 s and then 16 cycles of the following: 12 s at ambient temperature, then in <2 s the temperature will steadily increase (ramp) until reaching their pain temperature (determined by the calibration trials), and remain at that temperature (hold) for 5 s, followed by a variable inter stimulus interval of 12–20 s. Following the 16th cycle, the scan proceeds for another 30 s with the thermode at ambient temperature. |
*Given that our previous clinical trial20 evaluating CBT-I relative to a waitlist control on sleep and pain and arousal outcomes found large effect sizes for CBT-I-related improvement in DBAS-assessed cognitive-affective arousal related to sleep, we used the same measure in this trial as well. However, another important index of presleep arousal (including somatic and cognitive arousal) could be captured by using the Pre-Sleep Arousal Scale (PSAS).88 Thus, we will consider using the PSAS in future trials.
AC-PC, anterior commissure-posterior commissure ; DWI, diffusion weighted imaging; EOG, electrooculography; EPI, echo planar imaging ; ET, echo time; FOV, field of view; TR, repitition time.