A Transdiagnostic Sleep and Circadian Treatment to Improve Community SMI Outcomes

Despite advances in treatment, severe mental illness (SMI) remains common, chronic and difficult to treat. SMI is defined as having at least one mental disorder that lasts for 12-months and leads to substantial life interference. Sleep and circadian dysfunctions are among the most prominent correlates of SMI, yet have been minimally studied in ways that reflect the complexity of the sleep problems experienced by people with SMI. In SMI, sleep and circadian dysfunction undermines affect regulation, cognitive function and physical health, predicts onset and worsening of symptoms and is often chronic even with evidence-based SMI treatment. Prior treatment studies have been disorder-focused-they have treated a specific sleep problem (e.g., insomnia) in a specific diagnostic group (e.g., depression). However, real life sleep and circadian problems are not so neatly categorized, particularly in SMI where features of insomnia overlap with hypersomnia, delayed sleep phase and irregular sleep-wake schedules. Accordingly, the investigators aim to test the hypothesis that a Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) will improve functional impairment, disorder-focused symptoms and sleep and circadian functioning. The investigators will recruit participants across Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses and across common sleep and circadian problems. The elements of TranS-C are efficacious across SMI in research settings with research-based providers. The next step is to test TranS-C in community settings with community-based providers. Accordingly, the investigators propose to conduct an 'efficacy in the real world' randomized controlled trial within Alameda County Behavioral Health Care Services (ACBHCS), the community mental health center (CMHC) for Alameda County. The investigators will recruit 120 adults diagnosed with SMI and sleep and circadian dysfunction within ACBHCS. Individuals will be randomly allocated to TranS-C (n = 60) or 6-months of Usual Care followed by Delayed Treatment with TranS-C (UC-DT; n = 60). TranS-C is modularized and delivered across eight to twelve 50-minute, weekly, individual sessions. All participants will be assessed before, immediately following treatment (ie. 9-14 weeks later) and again 6 months later.

• Transdiagnostic Intervention for Sleep and Circadian Dysfunction (Behavioral): The intervention is a modular treatment composed of core modules that are given to all participants and modules that are delivered based on the need/s of the participants. The interventions are all cognitive behavioral.

Primary outcomes

• Impairment (Sheehan Disability Scale) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Sheehan Disability Scale (SDS) (sleep). 3-item. The SDS evaluates the extent to which work/school, social life, and home/ family responsibilities are impaired on a 0-10 (not at all to extremely) scale. The 3-items are summed to compute the total score and assess global functional impairment. Scores can range from 0 to 30, with higher values indicating higher impairment.
• Disorder-Focused Composite Score (DSM-5) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: DSM-5 Cross Cutting Measure. 23-items. Individuals report how much each domain has bothered them in the last 2 weeks on a 0-4 scale (not at all to nearly every day). The total score is calculated by summing the highest score in each of the 13 domains (depression, anger, mania, anxiety, somatic symptoms, suicidal ideation, psychosis, sleep problems, memory, repetitive thoughts and behaviors, dissociation, personality functioning, and substance use). Total scores can range from 0 to 52, with higher scores indicating greater severity of impairment. is rated on a 5-point scale, with higher scores indicating more severe impairment.
• Sleep and Circadian Function: PROMIS-Sleep Disturbance [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: PROMIS-Sleep Disturbance (PROMIS = Patient-Reported Outcomes Measurement Information System). The 8-item short version assesses sleep disturbance over the past 7 days, including restlessness, sleep quality, ability to fall and stay asleep, and refreshment following sleep using a 1-5 scale (not at all or never to very much or always). Scores range from 8 to 40, with higher scores indicating increased disturbance.
• Sleep and Circadian Function: PROMIS-Sleep-Related Impairment [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: PROMIS-Sleep-Related Impairment (PROMIS = Patient-Reported Outcomes Measurement Information System). 16-item. Scores range from 16 to 80, with higher scores indicating increased disturbance.

Secondary outcomes

• Depression (QIDS) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: QIDS (Quick Inventory of Depressive Symptoms). 16-item instrument assessing depressive symptoms. Each item is rated on a 4-point scale (0-3), with higher scores indicating greater symptom severity. Scoring involves summing the highest score from each of the 9 DSM-IV Major Depressive Disorder symptom domains (sleep, weight, psychomotor changes, depressed mood, decreased interest, fatigue, guilt, concentration, and suicidal ideation). Total scores range from 0 (Normal/No Depression) to 27 (Very Severe Depression). Higher scores indicate greater severity of depressive symptoms.
• Substance Use (ASSIST ) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: ASSIST (Alcohol, Smoking and Substance Involvement Screening Test). Frequency of use, substance dependence, and related health, social, legal, financial, and employment problems in the past 3 months are rated on a 5-point scale (never to daily of almost daily). Problems with family and friends caused by substance use and failed attempts to cut down or quit substance use are measured on a 3-point scale (no, never, yes, in the past 3 months, yes, but not in the past 3 months). The total risk score is calculated by summing scores across all drug categories, with total scores ranging from 0 to 414. Higher scores indicate greater substance-related risks and problems.
• Psychotic Symptoms (PSYRATS ) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: PSYRATS (Psychotic Symptom Rating Scales). Each of the 17 items is rated on a 5-point scale from 0 (absent) to 4 (severe). Scores are summed for auditory hallucinations (sum of 11 items) and delusions (sum of 6 items). Total scores range from 0 to 68, with higher scores indicating greater severity of psychotic symptoms.
• Means and Variability of Sleep Efficiency (Daily Sleep Diary) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Sleep efficiency (SE), calculated as total sleep time divided by time in bed, multiplied by 100, was recorded via sleep diary over 7 consecutive days. For each participant, the mean and within-person standard deviation (SD) of SE were calculated across the days to reflect an average and night-to-night variability. Group-level outcomes reflect the average of these participant-level means and SDs.
• Actigraphy Measured Sleep (TST) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Actigraphy-derived total sleep time (TST) is the total amount of sleep obtained by the participant per 24 hrs, which was recorded daily over a 1-week period per timepoint. For each participant, the mean and standard deviation (SD) of TST were calculated across the days. Group-level outcomes reflect the average of these participant-level means and SDs.
• Daytime Activity (Actigraphy) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Daytime activity was measured via actigraphy over 7 consecutive days per timepoint. For each participant, their daily waking activity counts were extracted, and the mean and within-person standard deviation (SD) of these counts were calculated across 7 days. Group-level outcomes reflect the average of these participant-level means and SDs.
• Impairment (World Health Organization Disability Assessment Schedule 2.0) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: World Health Organization Disability Assessment Schedule 2.0 (WHODAS-2.0). 36-item measure that assesses disability in adults ages 18 years and older. It assesses disability across six domains on a scale from 1-5 (none to extreme or cannot do). Each item on the self-administered version of the WHODAS-2.0 asks the individual to rate how much difficulty he or she has had in specific areas of functioning during the past 30 days. Scores are summed across the six domains (cognition, mobility, self-care, getting along, life activities, and participation). Total scores range from 36 to 180, with higher scores indicating greater levels of disability.
• Overall Health ('Healthy Days' Core Module) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Four question 'healthy days' core module developed by the Centers for Disease Control and Prevention. A summary measure combines physically and mentally unhealthy days. An "unhealthy days" summary measure based on the second and third questions and estimates the overall number of recent days (in the past 30 days) when physical or mental health was not good.
• Composite Sleep Health Score [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Composite Sleep Health Score is defined as the sum of scores on 6 sleep health dimensions: Regularity (Midpoint sleep fluctuation across a 7-day sleep diary < 1 hour), Satisfaction (Sleep quality question on PROMIS-Sleep Disturbance (PROMIS = Patient-Reported Outcomes Measurement Information System)), Alertness (Daytime sleepiness question on PROMIS-Sleep Related Impairment (PROMIS = Patient-Reported Outcomes Measurement Information System)), Timing (Mean midpoint sleep across the 7 day sleep diary between 2 and 4 AM), Efficiency (Average sleep efficiency based on the 7 day sleep diary ≥ 85%), and Duration (Total Sleep Time average based on 7 day sleep diary between 7 and 9 hours). Each dimension was dichotomized such that 1 = good /yes; 0 = poor/no). Total composite sleep health score ranges from 0 to 6, with larger values indicating better sleep health.
• Means and Variability of Total Sleep Time (Daily Sleep Diary) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Total sleep time (TST), measured as the total amount of sleep obtained by the participant, was reported via sleep diary over 7 consecutive days. Each participant's mean and within-person SD of TST were calculated to assess typical sleep duration and night-to-night variability. Group-level outcomes reflect the average of these participant-level means and SDs.
• Means and Variability of Total Wake Time (Daily Sleep Diary) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Total wake time (TWT), measured as minutes of wakefulness within a sleep period, was reported via sleep diary over 7 consecutive days. Each participant's mean and within-person SD of their TWT were calculated across days to assess means and night-to-night variability. Group-level outcomes reflect the average of these participant-level means and SDs.
• Means and Variability of Bedtime (Daily Sleep Diary) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Bedtime was reported via a 7-day daily sleep diary using a 24-hour decimal format, where times after midnight are expressed as numbers above 24 (ex. 1:30 am is 25.50). Each participant's mean and within-person SD of bedtime across 7 days were computed to capture average bedtime and variability. Group-level outcomes reflect the average of these participant-level means and SDs.
• Means and Variability of Wake Time (Daily Sleep Diary) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Wake times, using a 24-hour decimal format, were reported daily across 7 days. The mean and within-person SD were calculated for each participant's wake time across days. Group-level outcomes reflect the average of these participant-level means and SDs.
• Actigraphy Measured Sleep (TWT) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]: Actigraphy-derived total wake time (TWT), measured as minutes of wakefulness within a sleep period, was collected daily over a 1-week period. Each participant's mean and within-person SD were calculated across the 7 days. Group-level outcomes reflect the average of these participant-level means and SDs.

Other outcomes

• Diagnosis of Psychiatric Disorders (MINI International Neuropsychiatric Interview ) [Documenting diagnosis at baseline, 10-14 weeks after the beginning of treatment, and 6-month follow-up, no change predicted]
• Diagnosis of Sleep Disorders (Duke Structured Interview for Sleep Disorder, DSM-V) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]
• Sleep and Circadian Problems Interview [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]
• Insomnia Severity Index [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]
• Hypersomnia Severity Index [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]
• Therapy Process Measure [Administered at the end of Session 2 of treatment]: Credibility Expectancy Questionnaire
• Medication and Other Treatment Tracking Form [Stability in baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month followup]
• Additional Screen for Sleep Apnea [Baseline Only]: Snoring, tiredness/sleepiness, observed apneas, hypertension, BMI > 35 kg/m2, age > 50 years, neck circumference > 40 cm, and male gender (STOP-BANG) Questionnaire. 8-item screen for obstructive sleep apnea.
• Brief Pain Inventory (Short Form) [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month follow-up]: Current symptoms of chronic pain
• Clinic Staff Qualitative Assessment [One time at the convenience of clinic staff]: Explore barriers and facilitators to implementing an evidence-based sleep treatment in a community setting
• Client Behavior Change Interview [One time following the completion of the first post-treatment assessment]: Exploration of barriers and facilitators to behavior change
• Salivary Cytokine Assay [Change from baseline to post treatment, which is 9-14 weeks after the beginning of treatment, and to 6-month follow-up]: Measure of cytokines present in saliva (e.g., Interleukin (IL) -1 beta, IL-6, IL-8, Tumor necrosis factor (TNF) alpha, and/or C-reactive protein (CRP)) to assess immune function
• Credibility Evaluation Questionnaire (CEQ) [Session 2 and Post treatment, which is 9-14 weeks after the beginning of treatment.]: Client evaluation of treatment
• Patient Recall Task [Post treatment, which is 9-14 weeks after the beginning of treatment, and 6-month follow-up]: Participant recall of sleep coaching treatment
• Patient Learning Task (Application and Thoughts Subsections) [Post treatment, which is 9-14 weeks after the beginning of treatment, and at 6-month follow-up]: Client feedback and application of treatment
• Useful and Utilized Questionnaire [Post treatment, which is 9-14 weeks after the beginning of treatment, and at 6-month follow-up]: Measure of sleep coaching elements used/useful to clients
• Treatment Adherence Rating Scale-Therapist Version [After each treatment session filled out by therapist (8 times)]: Therapist evaluation of client adherence to treatment
• Body Weight [Pre-treatment, post treatment, which is 9-14 weeks after the beginning of treatment, and at 6-month follow-up]: To calculate BMI
• Height [Pre-treatment]: To calculate BMI

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age 18+ years
* English language fluency
* Presence of at least one DSM-V mental disorder for 12 months
* One or more of the following sleep or circadian problems for 3 month as assessed with the Sleep and Circadian Problems Interview:

  * ≥30 mins to get to sleep , 3 or more nights per week
  * Waking in the middle of the night for ≥30 minutes, 3 or more nights per week
  * Obtaining less than 6 hours of sleep per night, 3 or more nights per week
  * Obtaining more than 9 hours of sleep per 24 hour period (i.e., nighttime sleep plus daytime napping), 3 or more nights per week
  * More than 2.78 hours of variability in sleep-wake schedule across one week
  * Bedtime later than 2 am, 3 or more nights per week
* Guaranteed bed to sleep in for the duration of the treatment phase
* Receiving care for SMI at ACBHCS and consent to regular communications between research team and psychiatrist and/or case manager

Exclusion Criteria:

* Presence of an active and progressive physical illness or neurological degenerative disease AND/OR substance abuse/dependence making participation in the study unfeasible.
* Current serious suicide risk (assessed by our staff, a case manager or psychiatrist) or homicide risk (assessed by our staff, a case manager or psychiatrist)
* Night shift work >2 nights per week in the past 3 months
* Pregnancy or breast-feeding
* Not able/willing to participate in and/or complete the pre-treatment assessments

Participant flow

Outcome results

• Impairment (Sheehan Disability Scale) (Primary), Mean, score on a scale: UC-DT 14.30 +/- 8.51; TranS-C 12.03 +/- 6.20 (p 0.025)
• Disorder-Focused Composite Score (DSM-5) (Primary), Mean, score on a scale: UC-DT 25.57 +/- 10.72; TranS-C 25.05 +/- 9.75 (p 0.001)
• Sleep and Circadian Function: PROMIS-Sleep Disturbance (Primary), Mean, score on a scale: UC-DT 29.02 +/- 6.57; TranS-C 28.26 +/- 6.06 (p <0.0001)
• Sleep and Circadian Function: PROMIS-Sleep-Related Impairment (Primary), Mean, score on a scale: UC-DT 51.02 +/- 14.09; TranS-C 47.93 +/- 11.80 (p <0.0001)
• Depression (QIDS) (Secondary), Mean, score on a scale: UC-DT 12.50 +/- 4.71; TranS-C 12.03 +/- 5.15 (p 0.32)
• Substance Use (ASSIST ) (Secondary), Mean, score on a scale: UC-DT 33.68 +/- 25.87; TranS-C 39.70 +/- 26.68 (p 0.72)
• Psychotic Symptoms (PSYRATS ) (Secondary), Mean, score on a scale: UC-DT 36.60 +/- 5.13; TranS-C 39.60 +/- 14.29 (p 0.73)
• Means and Variability of Sleep Efficiency (Daily Sleep Diary) (Secondary), Mean, percentage of sleep efficiency: UC-DT 77.61 +/- 11.89; TranS-C 77.39 +/- 13.52 (p 0.03)
• Actigraphy Measured Sleep (TST) (Secondary), Mean, Minutes: UC-DT 421.35 +/- 126.92; TranS-C 453.65 +/- 147.28 (p 0.59)
• Daytime Activity (Actigraphy) (Secondary), Mean, Activity counts: UC-DT 1309.74 +/- 532.79; TranS-C 1280.09 +/- 607.46 (p 0.34)
• Impairment (World Health Organization Disability Assessment Schedule 2.0) (Secondary), Mean, score on a scale: UC-DT 81.53 +/- 25.56; TranS-C 76.48 +/- 21.38 (p 0.09)
• Overall Health ('Healthy Days' Core Module) (Secondary), Mean, Days: UC-DT 3.57 +/- 1.17; TranS-C 3.44 +/- 1.03 (p 0.46)
• Composite Sleep Health Score (Secondary), Mean, Score on a scale: UC-DT 2.28 +/- 1.29; TranS-C 2.54 +/- 1.60 (p 0.002)
• Means and Variability of Total Sleep Time (Daily Sleep Diary) (Secondary), Mean, Minutes: UC-DT 452.42 +/- 101.37; TranS-C 431.06 +/- 111.47 (p 0.23)
• Means and Variability of Total Wake Time (Daily Sleep Diary) (Secondary), Mean, Minutes: UC-DT 131.89 +/- 80.47; TranS-C 124.84 +/- 75.03 (p 0.04)
• Means and Variability of Bedtime (Daily Sleep Diary) (Secondary), Mean, hours: UC-DT 22.20 +/- 1.95; TranS-C 22.17 +/- 2.36 (p 0.10)
• Means and Variability of Wake Time (Daily Sleep Diary) (Secondary), Mean, hours: UC-DT 7.90 +/- 1.83; TranS-C 7.31 +/- 2.02 (p 0.39)
• Actigraphy Measured Sleep (TWT) (Secondary), Mean, Minutes: UC-DT 91.06 +/- 41.52; TranS-C 94.95 +/- 55.18 (p 0.66)
• Diagnosis of Psychiatric Disorders (MINI International Neuropsychiatric Interview ) (Other pre specified)
• Diagnosis of Sleep Disorders (Duke Structured Interview for Sleep Disorder, DSM-V) (Other pre specified)
• 17 more outcome measures not shown.

Adverse events

Time frame: Through study completion, an average of 6 months.

• Results publication: Callaway CA, Sarfan LD, Gumport NB, Harvey AG. The impact of module dosage on treatment response in a modular transdiagnostic intervention for sleep and circadian dysfunction (TranS-C). Behav Res Ther. 2023 Sep;168:104368. doi: 10.1016/j.brat.2023.104368. Epub 2023 Jul 5. PMID 37478529
• Results publication: Harvey AG, Dong L, Hein K, Yu SH, Martinez AJ, Gumport NB, Smith FL, Chapman A, Lisman M, Mirzadegan IA, Mullin AC, Fine E, Dolsen EA, Gasperetti CE, Bukosky J, Alvarado-Martinez CG, Kilbourne AM, Rabe-Hesketh S, Buysse DJ. A randomized controlled trial of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) to improve serious mental illness outcomes in a community setting. J Consult Clin Psychol. 2021 Jun;89(6):537-550. doi: 10.1037/ccp0000650. PMID 34264701
• Results publication: Gumport NB, Yu SH, Harvey AG. Implementing a transdiagnostic sleep and circadian intervention in a community mental health setting: A qualitative process evaluation with community stakeholders. Psychiatry Res. 2020 Nov;293:113443. doi: 10.1016/j.psychres.2020.113443. Epub 2020 Aug 31. PMID 32890862
• Results publication: Harvey AG, Hein K, Dong L, Smith FL, Lisman M, Yu S, Rabe-Hesketh S, Buysse DJ. A transdiagnostic sleep and circadian treatment to improve severe mental illness outcomes in a community setting: study protocol for a randomized controlled trial. Trials. 2016 Dec 20;17(1):606. doi: 10.1186/s13063-016-1690-9. PMID 27998295

• Study Protocol and Statistical Analysis Plan (PDF, 2016-10-25)

• Allison G Harvey, PhD, Principal investigator, University of California, Berkeley