The Effects of Insomnia Treatment on Overnight Regulation of Emotional Memories and Risk for Mental Disorders (Restless)

A Delayed-start Randomized Controlled Trial Comparing the Effects of Online Therapist-guided Cognitive Behavioural and Circadian Therapy for Insomnia Versus Control on Overnight Emotion Regulation and Mental Health Outcomes

This project aims to elucidate whether CBCTi changes symptom severity or even remission of anxiety disorders as compared with a delayed-start control group. The investigators will use a delayed-start randomized controlled trial in a cohort of individuals with anxiety and insomnia (N=98) to compare the effects of an online therapist-guided cognitive behavioural and circadian therapy for insomnia versus control on overnight emotion regulation and mental health outcomes.

The project will involve at-home assessments and in-lab visits. At-home assessment involves recording sleep and circadian rhythm measures with wearables and daily diaries. Participants will be invited to perform two sleep studies and neuroimaging sessions to investigate the effects of CBCTi on neuroimaging and psychophysiological markers of overnight regulation of emotional distress.

Study Overview

• Status: Recruiting
• Conditions: Anxiety; Insomnia Chronic
• Intervention / Treatment: Behavioral: Immediate CBCTi; Behavioral: Delayed CBCTi

Detailed Description

This study is a delayed-start randomized controlled trial comparing the effects of online therapist-guided cognitive behavioural and circadian therapy for insomnia (CBCTi) versus control on emotional regulation and mental health outcomes.

To be enrolled in the study, the participants are required to complete an online prescreening survey followed by a telephone screening interview with further questions and to verbally explain to participants what is required of them in this study. After an interview screening, the participants will receive a finger-pulse oximeter by mail to screen for the presence of obstructive sleep apnoea (3 nights at-home). The device is then returned by pre-paid mail and the recording is analysed to screen for moderate to severe sleep apnoea (oxygen desaturation index ≥ 10). If eligible, the participant will be invited to the Woolcock Institute for a screening visit.

The screening visit starts with a consult with a clinician/physician who performs a medical screening, explains the study, answers questions and addresses concerns, and obtains written informed consent. At the end of the consult, all eligibility criteria have been evaluated and eligible participants are assigned a randomization number i.e., allocated to either the immediate CBCTi-arm or the delayed-start control-arm. The treatment arm consists of an online therapist-guided CBCTi intervention which comprises online sessions to be completed in 8 weeks. Participants in the delayed-start control arm in this study will not receive any active intervention during the first two months but will be offered the same therapist-guided CBCTi program thereafter

During the screening visit, participants will be asked to perform in an audio-visual recording while singing along to "Waltzing Matilda" (karaoke style) and asked to give keywords that relate to at least five negative distressing experiences and an equal number of neutral experiences from the same period. The recording and the keywords will be used to derive the stimuli that are used in the functional MRI tasks (Pre-Post CBCTi). The screening visit is concluded with a demonstration on how to collect data at-home.

Both groups will be asked to perform a week of at-home assessment during 4 timepoints: T0 (baseline), T1 (2 months post-baseline), T2 (4 months post-baseline) and T3 (12 months post-baseline). During the week of at-home assessments, the participants complete questionnaires, keep a sleep diary, and wear an actigraphy-watch, and light and temperature sensor (across 7 days). They are also asked to complete at least four overnight polysomnographic recordings using an EEG headband. At Pre and Post-CBCTi only, they also complete a salivary melatonin collection protocol.

At Pre and Post-CBCTi (i.e., T0 and T1 for immediate group - T1 and T2 for delayed group) , participants are invited to Macquarie University/Woolcock Institute to undergo overnight sleep studies and neuroimaging sessions.

The CBCTi program will be given online via secure platforms and recruitment will primarily be through social media advertisements. The study will be coordinated from the Woolcock Institute of Medical Research, Sydney, Macquarie Park, New South Wales, 2109, Australia.

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rick Wassing, PhD; Phone Number: +61 0298502663; Email: rick.wassing@woolcock.org.au
• Study Contact Backup: Name: Aurore Perrault, PhD; Email: aurore.perrault@mq.edu.au

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2109
      • Recruiting
      • Woolcock Institute of Medical Research
      • Sub-Investigator: Camilla Hoyos, PhD
      • Contact: Rick Wassing, PhD; Phone Number: 0298502663; Email: rick.wassing@woolcock.org.au
      • Contact: Greg Kaplan, A/Prof; Phone Number: 0298053232; Email: grigori.kaplan@woolcock.org.au
      • Principal Investigator: Rick Wassing, PhD
      • Sub-Investigator: Ron Grunstein, Prof
      • Sub-Investigator: Aurore A Perrault, PhD
      • Sub-Investigator: Delwyn Bartlett, A/Prof
      • Sub-Investigator: Christopher Gordon, A/Prof
      • Sub-Investigator: Nathaniel Marshall, A/Prof
      • Sub-Investigator: Craig Phillips, A/Prof
      • Sub-Investigator: Angela D'Rozario, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• (A or B) and (C) A. Diagnosis of insomnia disorder (DSM-5-TR) B. Insomnia Severity Index (ISI) score ≥ 10 C. Generalized Anxiety Disorder (GAD-7) score ≥ 10
• All sexes and genders.
• Between 18 and 45 years of age.
• Able to provide informed consent.
• Proficient in English.

Exclusion Criteria:

x Sleep or circadian disorder other than insomnia (e.g., hypersomnolence, periodic limb movement disorder, advanced or delayed sleep phase disorder, moderate to severe sleep apnoea disorder based on previous sleep study with an apnea-hypopnea index ≥ 15 and/or finger-pulse oximetry oxygen desaturation index (ODI) ≥ 10).

• Current or history of neurological disorders (e.g., stroke, brain injury).
• Current or history of bipolar disorder, psychosis, or moderate to severe obsessive-compulsive disorder.
• Current uncontrolled mental health disorders requiring specialist care, other than major depression and anxiety disorders.
• Centrally active agents or presence of medical condition that may affect participation.
• Pregnancy or actively trying to conceive, or lactating.
• Shift work for at least 2 shifts per week in the past 3 months (i.e., work between 21:00 and 6:00).
• Travel across time zones over 3 hours difference in the previous 30 days (will require a 1-day adjustment period per hour of time zone travelled).
• Unwilling to know about potential incidental findings.
• No consent or adherence to instructions for any part of the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immediate CBCTi; Immediate 8-weeks online therapist-guided CBCTi including weekly online modules. Guidance is provided via scheduled and ad hoc communications (e.g., email, messaging, telehealth) between the participant and a clinician/physician	Behavioral: Immediate CBCTi; This intervention will be immediately accessible to the CBCTi group. The program is composed of weekly online modules that include written information and interactive components such as schematics, images, videos, and questions. The content of the modules follows traditional and validated cognitive-behavioural therapy for insomnia protocols including sleep education, behavioural strategies (e.g., stimulus control, bedtime retraining, sleep hygiene), cognitive restructuration approaches (e.g., thought reappraisal, imagery, mindfulness), and relaxation practices (progressive muscle relaxation and autogenic training). In addition, further content aims to stabilize and amplify circadian rhythmicity through light exposure in the morning, daytime moderate physical activity, and evening time warm baths. Participants complete daily sleep diaries throughout the intervention.
Other: Delayed-start control; Participants in the delayed-start control group will not receive any active intervention during two months but will be offered the same therapist-guided CBCTi program thereafter.	Behavioral: Delayed CBCTi; This intervention will be accessible after a waiting period of 2 months (i.e, delayed start). The program is composed of weekly online modules that include written information and interactive components such as schematics, images, videos, and questions. The content of the modules follows traditional and validated cognitive-behavioural therapy for insomnia protocols including sleep education, behavioural strategies (e.g., stimulus control, bedtime retraining, sleep hygiene), cognitive restructuration approaches (e.g., thought reappraisal, imagery, mindfulness), and relaxation practices (progressive muscle relaxation and autogenic training). In addition, further content aims to stabilize and amplify circadian rhythmicity through light exposure in the morning, daytime moderate physical activity, and evening time warm baths. Participants complete daily sleep diaries throughout the intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
General Anxiety Disorder-7 (GAD-7) score	Self-report measures of anxiety symptoms and severity. GAD-7 consists of 7 Likert-scale questions with a total score ranging from 0 to 21 (with higher scores indicating more severe anxiety)	2 months, 4 months, 12 months
Anxiety Disorder diagnosis	Clinician-diagnosed anxiety disorder in accordance with the DSM-5-TR using the Mini-International Neuropsychiatric Interview	2 months, 4 months, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insomnia Severity Index (ISI) score	Self-report measures of insomnia symptoms and severity. ISI consists of 7 Likert-scale questions with a total score ranging from 0 to 28 (with higher scores indicating more severe insomnia)	2 months, 4 months, 12 months
EEG sleep efficiency (SE - %)	Mean SE derived from at-home sleep recordings (total sleep time/time in bed*100)	2 months, 4 months, 12 months
EEG total sleep time (TST - minutes)	Mean TST derived from at-home sleep recordings	2 months, 4 months, 12 months
EEG wake duration (minutes)	Mean wake after sleep onset (WASO) derived from at-home sleep recordings	2 months, 4 months, 12 months
EEG sleep onset latency (SOL - minutes)	Mean SOL derived from at-home sleep recordings	2 months, 4 months, 12 months
EEG sleep stages (%)	Mean time spent in sleep stages (per total sleep period) derived from at-home sleep recordings	2 months, 4 months, 12 months
Actigraphy sleep efficiency (%)	Mean SE derived from actigraphy recording (total sleep time/time in bed*100)	2 months, 4 months, 12 months
Actigraphy total sleep duration (minutes)	Mean TST derived from actigraphy recordings	2 months, 4 months, 12 months
Actigraphy wake duration (minutes)	Mean WASO derived from actigraphy recordings	2 months, 4 months, 12 months
Actigraphy sleep onset latency (minutes)	Mean SOL derived from actigraphy recordings	2 months, 4 months, 12 months
7-days light exposure (lux)	derived from at-home continuous light recording during the day	2 months, 4 months, 12 months
Hour of Dim-Light Melatonin Onset (HDLMO - hour)	derived from at-home collection of saliva samples	2 months
3-days distal-proximal skin-temperature gradients (DPG)	derived from at-home collection of continuous skin temperature (4 locations)	2 months, 4 months, 12 months
Self-reported sleep duration (min)	Mean TST derived from sleep diaries	2 months, 4 months, 12 months
Self-reported wake duration (min)	Mean WASO derived from sleep diaries	2 months, 4 months, 12 months
Self-reported sleep onset latency (min)	Mean SOL derived from sleep diaries	2 months, 4 months, 12 months
Self-reported sleep quality (out of 5)	Mean sleep quality derived from sleep diaries on a scale from 0 to 4 (very poor sleep to very good sleep)	2 months, 4 months, 12 months
Sleep misperception index (SPI - %)	SPI derived from subjective TST and objective TST (Subj/Obj*100)	2 months, 4 months, 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep electroencephalographic (EEG) spectral power	derived from polysomnographic (PSG) recordings in-lab: absolute and relative spectral power for band frequencies: slow oscillations (0.25-1.25Hz), delta (0.25-4Hz), theta (4.25-8Hz), alpha (8.25-11.75Hz), sigma (12-16Hz), low beta (16.25-19Hz), high beta (19.25-35Hz) for all stages.	2 months
Sleep electroencephalographic (EEG) neuro-oscillatory coupling	derived from PSG recordings in-lab - phase-amplitude coupling measures (modulation index, preferred phase)	2 months
Functional connectivity patterns in resting-state brain networks	measured by network-wise dual-regression independent component analysis (FMRIB FSL) with the whole-brain voxel-wise connectivity strength is the dependent variable	2 months
EEG sleep-related brain oscillations (characteristics)	EEG neurophysiological events derived from PSG recordings in-lab : density, duration, peak frequency, amplitude, number	2 months
Brain activation during tasks using functional magnetic resonance imaging	Whole-brain voxel-wise brain activation maps of the blood-oxygen dependent signal response to emotional stimuli during the Karaoke and Autobiography tasks.	2 months

Collaborators and Investigators

• Sponsor: Woolcock Institute of Medical Research
• Collaborators: Macquarie University, Australia
• Investigators: Principal Investigator: Rick Wassing, PhD, Woolcock Institute of Medical Research

Publications and helpful links

General Publications

• Bastien CH, Vallieres A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 Jul;2(4):297-307. doi: 10.1016/s1389-9457(00)00065-4.
• Hertenstein E, Feige B, Gmeiner T, Kienzler C, Spiegelhalder K, Johann A, Jansson-Frojmark M, Palagini L, Rucker G, Riemann D, Baglioni C. Insomnia as a predictor of mental disorders: A systematic review and meta-analysis. Sleep Med Rev. 2019 Feb;43:96-105. doi: 10.1016/j.smrv.2018.10.006. Epub 2018 Nov 16.
• Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Goncalves M, Hertenstein E, Jansson-Frojmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weess HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017 Dec;26(6):675-700. doi: 10.1111/jsr.12594. Epub 2017 Sep 5.
• Taylor DJ, Pruiksma KE. Cognitive and behavioural therapy for insomnia (CBT-I) in psychiatric populations: a systematic review. Int Rev Psychiatry. 2014 Apr;26(2):205-13. doi: 10.3109/09540261.2014.902808.
• Leerssen J, Lakbila-Kamal O, Dekkers LMS, Ikelaar SLC, Albers ACW, Blanken TF, Lancee J, van der Lande GJM, Maksimovic T, Mastenbroek SE, Reesen JE, van de Ven S, van der Zweerde T, Foster-Dingley JC, Van Someren EJW. Treating Insomnia with High Risk of Depression Using Therapist-Guided Digital Cognitive, Behavioral, and Circadian Rhythm Support Interventions to Prevent Worsening of Depressive Symptoms: A Randomized Controlled Trial. Psychother Psychosom. 2022;91(3):168-179. doi: 10.1159/000520282. Epub 2021 Dec 6.
• Wassing R, Lakbila-Kamal O, Ramautar JR, Stoffers D, Schalkwijk F, Van Someren EJW. Restless REM Sleep Impedes Overnight Amygdala Adaptation. Curr Biol. 2019 Jul 22;29(14):2351-2358.e4. doi: 10.1016/j.cub.2019.06.034. Epub 2019 Jul 11.
• Wassing R, Schalkwijk F, Lakbila-Kamal O, Ramautar JR, Stoffers D, Mutsaerts HJMM, Talamini LM, Van Someren EJW. Haunted by the past: old emotions remain salient in insomnia disorder. Brain. 2019 Jun 1;142(6):1783-1796. doi: 10.1093/brain/awz089.
• Lancee J, van Straten A, Morina N, Kaldo V, Kamphuis JH. Guided Online or Face-to-Face Cognitive Behavioral Treatment for Insomnia: A Randomized Wait-List Controlled Trial. Sleep. 2016 Jan 1;39(1):183-91. doi: 10.5665/sleep.5344.
• Berntsen D, Hoyle RH, Rubin DC. The Autobiographical Recollection Test (ART): A Measure of Individual Differences in Autobiographical Memory. J Appl Res Mem Cogn. 2019 Sep;8(3):305-318. doi: 10.1016/j.jarmac.2019.06.005. Epub 2019 Jul 26.
• Christensen H, Batterham PJ, Gosling JA, Ritterband LM, Griffiths KM, Thorndike FP, Glozier N, O'Dea B, Hickie IB, Mackinnon AJ. Effectiveness of an online insomnia program (SHUTi) for prevention of depressive episodes (the GoodNight Study): a randomised controlled trial. Lancet Psychiatry. 2016 Apr;3(4):333-41. doi: 10.1016/S2215-0366(15)00536-2. Epub 2016 Jan 28.

Study record dates

Study Major Dates

• Study Start (Estimated): January 6, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: insomnia; anxiety; online cognitive behavioral and circadian therapy for insomnia
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Anxiety Disorders; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: 14308; 227100/Z/23/Z (Other Grant/Funding Number: Wellcome Trust); GNT1196636 (Other Grant/Funding Number: National Health and Medical Research Council)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All study team members have access to the dataset. Other Woolcock-affiliated staff may also request access to the non-identifiable dataset, which will be considered by the principal investigator and co-investigators. A copy of the non-identifiable dataset may be requested by academic collaborators not affiliated with the Woolcock through a data request form, which outlines the investigators, aims and hypotheses, data to be included, a statistical analysis plan, ethics approval, and security measures.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No