Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06097221 |
| Other study ID # |
ADVANCE |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2024 |
| Est. completion date |
July 2026 |
Study information
| Verified date |
April 2024 |
| Source |
Mental Health Services in the Capital Region, Denmark |
| Contact |
Anne Sofie Kvist Houby, MD |
| Phone |
28780878 |
| Email |
anne.sofie.kvist.houby[@]regionh.dk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
150 patients with moderate to severe depression, recently discharged from a psychiatric ward
and now recieving treatment at an outpatient unit at Mental Health Center Copenhagen, will be
randomised in to two groups. A treatment ad usual (TAU) group and an Advance-group. The
Advance-group will receive a psychotherapeutic intervention focusing on advancing sleep
timing to improve depression.
Description:
Objective Patients treated at outpatient psychiatric services for major depression improves
slowly from their depression despite use of psychopharmacological, psychological, and
supportive methods. This is in many cases due to severe sleep disturbances as part of their
current depressive episode. Typically, these patients have difficulties keeping their
habitual sleep-wake cycle, that drifts to later in the evening and morning. Thus, patients
who, before being depressed, sleeps around 11 PM and wake up around 7 AM, often drift to a
later sleep schedule at around 1 AM and a wake-up time at 9 AM or even later during their
depressive period. The reason for the drift of the sleep schedule is mainly caused by reduced
signals to the circadian system from daylight, social input, dieting and exercise. This
reduced input is partly a result of the changed behavior of patients due to their depressive
symptoms making them less structured, less socially active, less physically active, eating
erratically, and staying more indoors thereby receiving less daylight. Another reason for the
sleep drift is the presence of diurnal variation of depressive symptoms with morning
worsening and evening improvement tempting patients to stay up later because of the better
evening mood. The sleep drift makes patients out of synchrony with societal and workplace
rhythms, and the investigators have clinical and research evidence for mood worsening
associated with sleep drift and of improvement of depression when patients correct their
sleep drift.
The physiological background behind why late sleep worsens and maintain depression is thought
to be caused by a sleep induced inhibition of the raphe nuclei in the brain stem
downregulating the serotonergic activity in the forebrain in the late phase of the sleep
period.
The association between depression and sleep/sleep timing is well established from the bulk
of literature on sleep deprivation, and sleep phase advance. Regulation of sleep disturbances
thus has a great potential as a specific new treatment target.
Our recent study showed that a newly developed psychoeducation method, Circadian
Reinforcement Therapy (CRT) could prevent sleep drift and improve mood in patients discharged
from inpatient wards. The standard psychoeducation manuals used at psychiatric services do
not focus adequately on the relation between signals to the circadian system, sleep timing,
and mood. The principle in the CRT is based on scientific findings that sleep timing and thus
mood is for a large part a result of how the actual day is spend - what signals is reaching
the circadian system. The influence of light during the day is termed Prior Light History and
has been documented to influence sleep, circadian rhythms, and melatonin
secretion/suppression. The main time signals to the circadian system (zeitgebers) are light
(electrical or daylight), social activity, exercise, and diet. The CRT method aimed to
strengthen all these time signals and normalize the sleep timing leading to improvement of
depression.
The objective of this project is to investigate whether the use of an adjusted CRT method
named CRT-Advance focusing even more on advancement of the sleep-wake cycle can induce an
antidepressant effect in selected patients that have drifted in their sleep during their
depressive episode (enriched sample).
The Advance method acknowledges the importance of clinical contact between project staff and
patients. In addition, patients will be asked to wear activity watches that measures light
exposure and sleep/wake timing. Tracking participants individual behavior by accelerometers
helps to reveal the invisible timing of the circadian system.
If the CRT-Advance method is effective, it can be established on a wider scale in
psychoeducation manuals and guidelines for depression and the method can have a potential for
psychiatric services making their treatment more cost-effective. An important point is that
traditional treatment methods such as pharmacotherapy and psychotherapy is less effective in
the presence of significant sleep problems due to daytime sleepiness and the depressiogenic
effect of mistimed sleep.
On a societal scale, there is a large need for treatments for insomnia, and the investigators
also expect the CRT-Advance method to improve insomnia by reducing sleep onset problems
through the advancement of sleep timing. This could reduce the use of dependence inducing
hypnotics.
The number of non-pharmacological treatment methods are now growing as psychotropic drugs
often are often associated with severe side effects and often a lack of efficacy. Therefore,
there is a need for the testing of novel treatment methods based on existing theoretical
background.
Chronotherapy has provided evidence based new treatment options like light therapy, wake
therapy, sleep time stabilization, and lately dark therapy. The chronotherapeutic research
field consists of a growing number of international research groups and societies, largely
interdisciplinary, with basic researchers and clinicians around the world.
The investigators also see a steady growth in the interest of chronotherapeutic application
in Denmark (https://psy.au.dk/en/circadianpsychology).
With several new professorships in the field, this proposed project is highly likely to
inspire the field further, making it easier to attract funding for research positions and
international collaboration.
Methods The design is a randomised clinical trial (RCT), where participants with major
depression and delayed sleep timing will be randomised into either a treatment as usual (TAU)
group or a CRT-Advance group using psychoeducation methods to reset sleep timing to earlier.
The CRT-Advance method is based on the use of (1) sleep diaries, (2) zeitgebers diaries
diaries capturing time signals to the circadian system e.g. daylight, social contact, meals,
and exercise), (3) close clinical weekly contact with focus on the result on sleep and mood
of the psychoeducative method.
Actigraphy is recorded with the MotionWatch 8 (MW8, Camntech, UK), which provides an
objective measure of sleep timing, 24-hour activity, night-sleep duration, night awakenings,
sleep efficiency, day-time napping, and light exposure. Its algorithms on sleep have been
validated against polysomnography.
The MW8 is a wristwatch-like device that monitors activity levels and light levels for
continuous periods, using accelerometer and light sensing technology. Specialised software
(MotionWare Software) analyses data on sleep and circadian activity. Data can be directly
downloaded from the watch using a simple USB cable. The MotionWatch 8 will be handed over at
inclusion with detailed instructions. During the recording period, the participants will be
encouraged to wear the watch continuously day and night. Patients are informed to use the
marker button on the device to indicate when they intent to go to sleep (puts away
book/phone/etc. and turns off lights). The investigator will download data at each study
visit.
Psychoeducation material will be provided individually as part of the weekly clinical
contact.
Patients will be followed weekly for eight weeks, thus each patient will receive nine
sessions during the project - first visit on day 0, here after one visit every week for eight
weeks. The patients must show up at the outpatient treatment unit for the sessions at day 0,
week 2, week 4, week 6 and week 8 (final visit). The sessions at week 1, week 3, week 5 and
week 7 will be offered as physical meetings as well but can be done over the phone if this is
better for the patient.
The primary outcome is change in Hamilton Depression rating scale (HAM-D6) scores from
baseline to endpoint (self-rating).
Secondary outcomes are changes in sleep-midpoint, sleep onset and wake-up time from baseline
to endpoint from the sleep diaries and based on activity tracking with the MotionWatch 8.
Exploratory outcomes are scores change from baseline to endpoint on the following
questionnaires:, Pittsburgh Sleep Quality Index (PSQI, self-rating), WHO Five Well Being
Index (WHO-5, self-rating), Insomnia Severity Index (ISI, self-rating), Dysfunctional
Believes and Attitudes about Sleep (DBAS, self-rating), Epworth Sleepiness Scale (ESS,
self-rating) and Morningness-Eveningness Questionnaire (MEQ, self-rating). Furthermore, the
investigators will describe light exposure in the two groups. The sensors will be able to
discern when patients are in daylight. The investigators will also describe results from the
sleep diaries and the chrono-schedule.
All patients will use the Motion Watch 8 for implementing and validating changes of sleep
timing. Adverse events will be monitored. The project will follow GCP regulations and will be
approved by the Ethical Committees and the Danish Data Protection Agency.
