Clinical trial NCT06351839: Sleep Well Despite Persistent Pain Symptoms
Official title: Metacognitive Behavioral Therapy Integrated in Sleep Treatment for Comorbid Insomnia in Patients With Persistent Pain: A Randomized Controlled Semi-Crossover Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Insomnia Chronic
Insomnia Due to Medical Condition
Pain, Chronic
Keywords: Insomnia
Comorbid insomnia
Chronic pain
MetaCognitive Therapy for Insomnia
Sleep Hygiene
Sleep Education
Sleep Restriction
Group therapy
Lead sponsor: University of Tromso
Sponsor class: OTHER
Collaborators: name: University Hospital of North Norway
name: Diakonhjemmet Hospital
First posted: 2024-04-08
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: We randomize patients to receive either the Sleep-Well intervention or to the TAU condition (active waiting-list group). After 3 months, the TAU patients cross over and receive the Sleep-Well intervention; hence, the design is semi-crossover.
Primary purpose: TREATMENT

Brief summary: Background: The prevalence of comorbid insomnia is 8-10 times higher in patients with chronic pain than in the general population. Insomnia adds a considerable burden as it worsens the quality of life, restoration and repair, mental health and pain symptoms. Since pain and sleep problems are mutually reinforcing, improvements in sleep may have beneficial effects on pain. Unfortunately, the customary use of sleep medication (TAU: treatment-as-usual) often yields short-lived plus side effects. The "Sleep-Well" intervention examines if a group-based intervention program focusing on sleep literacy, sleep restriction, stimulus control and metacognitive therapy modules may perform better than TAU in improving patients' insomnia and sleep quality.

Eligible patients: Investigators target adult patients referred to the University Hospital of North Norway (Tromsø) for a diagnostic evaluation of their pain condition. Patients eligible for the Sleep-Well study are those who satisfy diagnostic criteria for a non-malign pain disorder plus a comorbid insomnia sleep disorder. Patients are not eligible if they use drugs or large doses of morphine (\>100 equivalents), are engaged in an insurance case due to their diagnosis, or participate in other ongoing group programs at the hospital.

Aims: This trial uses a randomized semi-crossover design to examine if the Sleep-Well group does better regarding insomnia and sleep quality than the control patients (TAU). The primary outcome measures are reductions in diagnostic criteria for insomnia, self-reported insomnia symptoms, quality of life, and actigraphy-measured insomnia indicators (long sleep onset latency, frequent nightly awakenings and early morning awakening). The secondary outcome measures include a simplified polysomnography measurement of brain activity during sleep to assess if proportions or durations of slow-wave versus light-wave sleep and EEG-based arousal indices improve. In addition, it is examined if the Sleep-Well intervention incurs benefits concerning pain complaints, dysfunctional sleep and pain cognitions, anxiety and depression.

The intervention: The Sleep-Well program schedules group sessions that cover four topics (sleep literacy, behavioural and mental strategies, maintenance and relapse prevention). All sessions are led by two therapists. Those randomized to the active control group (TAU) cross over to the Sleep-Well intervention three months later.

Detailed description: Background: Insomnia is 8-10 times more prevalent among patients with chronic pain than in the general population. The disrupted sleep restoration caused by insomnia can be exhausting for the patient as insomnia also impairs pain inhibition. Sleep medications often yield short-lived clinical responses and further introduce risks of "hangover", tolerance, and even addiction. Psychological sleep treatment is thus clearly preferable given sufficient effect.

Cognitive Behavioral Therapy is the recommended first-line treatment of insomnia (CBT-i). Psychological interventions are also recognized in the treatment and follow-up of chronic pain. However, the evidence of psychological treatment of comorbid insomnia in patients with chronic pain is very limited, although some few results are promising .

Insomnia is the most common sleep disorder and involves nocturnal symptoms (e.g. long sleep onset latency, nightly awakenings, and early morning awakening) and daytime problems (e.g. fatigue, mood swings, concentration difficulties, impaired function at work, school, or in social life). Acute insomnia symptoms triggered by adverse life events or acute illnesses are normal, whereas the transition to chronic insomnia is not. Chronic pain is a chronic stressor and may act both as a precipitating and perpetuating factor for insomnia, generating high levels of stress-activating hormones.

Rumination on the causes of pain is frequently observed in chronic pain, often combined with a cognitive inclination towards catastrophizing (i.e., repetitive, intrusive, and difficult-to-ignore thoughts). Meta-cognitions, such as rumination and catastrophizing may perpetuate insomnia by maintaining a high level of sleep-disruptive psychophysiological arousal and loss of deep sleep. Affective and anxiety disorders are other frequent comorbidities of chronic pain, that may further aggravate the effects of rumination and catastrophizing on both sleep and pain.

Meta-Cognitive Therapy (MCT) has well-documented effects on depression and anxiety disorders. Studies of MCT in insomnia are limited, which is unfortunate as it seems to modulate symptoms substantially across multiple health conditions. The advantage of MCT is the focus on how one relates to, evaluates, monitors, or reacts emotionally to internal thoughts rather than their specific content or experienced truth as in CBT. Change in dysfunctional cognitions about sleep is a central element of CBT-i. The strong association between insomnia and sleep-related metacognitions (thought patterns), rather than negative sleep-related cognitions (thought content), suggests that psychological treatment of insomnia should include MCT.

The sleep intervention for the present intervention study (hereafter "Sleep-Well") applies a modified version of a Norwegian CBT-i manual by the Diakonhjemmet hospital in Oslo, integrating elements of MCT. Sleep-Well is group-based and covers four modules; i.e. 1 (introduction), information about sleep physiology, causes of sleep problems, sleep hygiene and the use of sleep diaries; 2 (behavioral strategies), concerns stimulus control and sleep restriction; 3 (cognitive strategies) represent a CBT/MCT part focusing on sleep-disturbing cognitions and metacognition common to pain and sleep; and 4, maintenance and prevention of relapse.

Hypotheses: This trial examines if the Sleep-Well intervention performs better than the "treatment as usual" (TAU) group, i.e., rudimentary sleep evaluation and education plus sleep medication on indication, in terms of statistically significant improvements in:

1. (primary hypotheses) self-reported insomnia symptoms, diagnostic criteria for insomnia, health-related quality of life, and actigraphy recorded indicators of insomnia (i.e., SOL-sleep onset latency, WASO-wakeup after sleep onset, EMA-early morning awakening and SE-sleep efficiency).
2. (secondary hypotheses) self-reported symptoms of fatigue, symptoms of anxiety and depression, pain-symptoms related to acceptance, intensity and interference, and need for sleep medication. In addition, improvements in objective sleep recordings (the Home Sleep Test) related to the proportion and duration of slow-wave sleep periods, and sleep disturbance as indicated by the EEG-based arousal-index.

In addition, this trial explores

* whether mediator variables as described in the Measurement Outcomes section (under other variables) may identify treatment mechanisms related to the Sleep-Well program.
* through qualitative interviews participants' perceived feasibility and acceptability of Sleep-Well, and if qualitative contrasts are present between those benefitting well versus poorly with regard to primary insomnia symptoms.

Study design and procedures: This study uses a randomized semi-crossover design. Participants are randomized to the Sleep-Well or the active treatment-as-usual (TAU) comparator condition receiving standard sleep treatment at the hospital or their general practitioner. Participants are block randomized (block size = 4) to maintain equal treatment and TAU group sizes. After three months of waiting time, the TAU participants cross over to the Sleep-Well group.

The outcome measurements are registered at baseline (before the randomization), and after finishing the Sleep-Well intervention (posttest \~3 months). In addition, we conduct two follow-ups at three and 12 months to examine relapse. The TAU group carries out two pre-tests (before randomization, and before initiation of Sleep-Well) to control for sleep function changes during the waiting period.

Statistical power and analyses Power calculation: A meta-analysis of comparable somatic diagnoses (5 studies) indicated a standardized mean difference (Cohen´s d) between intervention and control ranging between 0.60-0.80 (Tang et al., 2015). With randomization done on an individual level, a correlation = 0.5 between pre- and post-test (R-sq=25%), alpha = 0.05, power = 0.80, and minimum Cohen´s d = 0.60, at least N = 68 patients are required to reject the null hypothesis. With an estimate of ICC (intra-class correlation) = .05 (adjustment for similarities that occur between patients due to sharing of a treatment group, cluster size=6), which yields a design effect of 1.25 (1+(6-1)\*ICC), at least N = 85 participants are needed. By adding a safety margin of 20% dropout, the final sample estimate is N = 106 patients.

Statistical analyses: Generalized linear mixed models (GenLinMixed) are used as a general rule due to great flexibility in handling both continuous, binary, and count-based outcome variables, and estimation of random effects for adjustment purposes due to dependency in the outcome measures at different levels (e.g. repeated data, treatment group clusters). The analyses are carried out conservatively as intention-to-treat. Alpha \< .05 and .01 are assumed for the hypotheses about primary sleep treatment outcomes (insomnia, sleep quality) and secondary/exploratory treatment effects (affective health, fatigue, quality of life) and moderators/mediators, respectively.

Qualitative analyses: The transcribed semi-structured interview data will be analyzed using the reflexive thematic analysis methodology, which across five steps seeks to identify the number of overall conceptual dimensions that meaningfully account for all the interview texts. The Consolidated Criteria for Reporting Qualitative Research will be applied.

Interaction with user representatives: The project has included two user representatives with first-hand experiences with chronic pain. They actively participate in multiple parts of the research process and are particularly consulted in questions related to relevance (e.g., regarding questionnaires and the content of Sleep-Well), the process of implementing the Sleep-Well intervention, and on issues related to avoiding over-burdening the participants.

Ethics: The Sleep-Well study has been approved by the Regional Committee for Medical and Health Research Ethics (CaseID: 500457). The project is assessed by the Center for Information Security and Privacy in Research (SIKT), and the Privacy Commissioner at UiT The Arctic University of Norway regarding Data Protection Impact Assessment (DPIA). Initiation of the study will be pending upon approval by all parties.

Eligibility criteria: Inclusion Criteria:

* Patients who, after clinical examination at University hospital of Northern Norway (UNN) fill the criteria for a chronic non-malignant pain diagnosis according to ICD-10.
* Satisfy criteria for a comorbid insomnia
* Both first-time referrals and former referred patients.

Exclusion Criteria:

* A comorbid drug abuse diagnosis (ICD-10)
* An ongoing compensation and/or insurance case related to a health issue, illness or treatment
* Drug treatment using \>100 morphine equivalents
* Participation in other group-based treatments at the UNN Pain Department or the Physical Outpatient Medical Clinic (must be completed before inclusion)

Primary outcomes:
measure: Insomnia symptoms
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months.
measure: Insomnia diagnosis
timeFrame: Baseline and post-test (3 months)
measure: Actigraphy insomnia indicators (SOL, WASO and EMA in minutes)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months.
measure: Actigraphy insomnia indicators (SE %)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months.
measure: Sleep diary insomnia indicators (SOL, WASO and EMA in minutes)
timeFrame: Between baseline and post-test (3 months): Five repeated measures across five weeks
Secondary outcomes:
measure: Sleep brain activity as measured by a simplified polysomnography device, i.e., a Home Sleep Test (HST)
timeFrame: Baseline and post-test (3 months)
measure: Anxiety and depression (HADS)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
measure: Quality of Life (EQ-5Q-5L)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
measure: Fatigue (Chalder Fatigue Scale)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
measure: Pain intensity, interference and locations (BPI)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
measure: Tolerance and Acceptance of chronic pain (CPAQ-R)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
Other outcomes:
measure: Mediator: Sleep hygiene (SHI)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
measure: Hyperactivity (HAS)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
measure: Mediator: Dysfunctional beliefs and attitudes about sleep (DBAS)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
measure: Mediator: Metacognitions about insomnia (MCQ-i)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
measure: Mediator: Insomnia catastrophizing Scale (ISC)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
measure: Mediator: Pain Catastrophizing Scale (PCS)
timeFrame: Baseline and post-test (3 months), plus follow-up at 3 and 12 months
Locations:
city: Tromsø
country: Norway
facility: UiT The Arctic University of Norway
state: Troms county
Study officials:
affiliation: UiT The Arctic University of Norway
name: Oddgeir Friborg, PhD
role: PRINCIPAL_INVESTIGATOR
References: