An integrated approach to sleep improvement

Insomnia is a condition that affects about 10% of the Western population.
insomnia has severe consequences for health (increased risk of depression,
obesity and cardiovascular problems) and society (reduction in productivity,
increased sick leave and care request). These consequences place a high
economic burden on the health care system and society. Adequate treatment is
necessary.

At present, the most common solution provided by primary care givers (general
practitioners) is pharmacological treatment. However, pharmacological
treatments have a high prevalence of negative side effects, such as daytime
drowsiness, risk of abuse and addiction, and rebound insomnia on withdrawal.
Two more recently developed treatments are chronobiological treatment (CT) and
cognitive behavioral therapy (CBT). They appear safer and have more sustained
effects.

A problem facing implementation of CBT-I is that there are hardly any skilled
therapists. Web-based CBT-I may this alleviate this problem. A second
opportunity for optimization of treatment is based on the contention that the
people with insomnia most likely represent a heterogeneous mix of different
subtypes, with different underlying causes and expected treatment response.
These subtypes, or phenotypes, may not only be distinguished by type of sleep
problems. Other factors such as personality traits, medical complaints and
medical history, the ability to perceive comfort etc. may play a role as well.
Currently our research group is conducting a large-scale study using web-based
questionnaires to collect data on these factors (the Netherlands Sleep
Registry, NSR, www.slaapregister.nl). The use of latent class analysis on these
data will allow for the classification of participants into different
phenotypes.

This is the first step in the development of a protocol for individualized
optimal treatment for specific phenotypes of insomnia, where each phenotype may
show different CT and CBT-I demands. The project described in this protocol
will define the optimal treatment for the four most prominent phenotypes found
in the NSR study. In a systematic way the effectiveness of CT, CBT-I and their
combination will be evaluated. Additionally, this study will evaluate whether
insomnia subtype moderates the effectiveness of the individual and combined
treatments

Primary objectives:
* To evaluate the relative effectiveness of web-based CBT-I and three different
types of CT (light, temperature and physical activity) and their interaction as
compared to placebo treatment.
* To evaluate whether different phenotypes of chronic insomnia respond
differently to individual and combined treatments mentioned above.
Secondary objectives:
* To evaluate whether the effect of CBT-I is enhanced by prior CT.
* To evaluate the cost effectiveness of CT, CBT-I and their combinations.
* To evaluate whether CBT-I and CT or a combination or a combination thereof
approve long-term (after 3 years) behavioral changes.
* To evaluate the long-term (after 3 years) effects of CBT-I and CT or a
combination thereof on insomnia and affect.

The study is a double blind, randomized, placebo controlled clinical trial. 160
participants will be recruited through the NSR, who will be randomly assigned
to each one of eight limbs in a repeated measures design with two factors
(CBT-I and CT) of respectively 2 (active treatment versus waitlist monitoring)
and 4 (light, physical activity, body warming and placebo) levels. This yields
8 groups of 20 participants. Assessment will be done at baseline, at the end of
a four-week treatment period (last week of treatment and the week after) and at
the end of a four-week follow-up period. There will be a follow-up measurement
after three years.

CBT-I.
All participants will receive web-based, personalized cognitive behavioral
treatment (SOMNIO), the first treatment factor, for four weeks. Half of the
participants will be randomized to receive the CBT-I during the first four
weeks after the baseline assessment; the other half to a waitlist for CBT-I.
Cognitive behavioral therapy (CBT) is a combination of psychological and
behavioral treatments. When these treatments focus on sleep improvement, the
term CBT-I is often used (cognitive behavioral therapy for insomnia). CBT-I
combines stimulus control (i.e. association of bed with sleeping), sleep
restriction (i.e. restrict time in bed to average sleep time), relaxation
training, cognitive therapy (i.e. change misconceptions about sleep) and sleep
hygiene (e.g. general guidelines about health and environmental factors
influencing sleep). For ethical reasons, the participants that were randomized
to be at a waitlist for CBT-I , will receive it afterwards, in week 7 to 10.

CT.
During the first four weeks after the baseline assessment (week two to five,
see table 1 and figure 1), participants will be randomized to one of the four
CT treatment conditions listed below, forming the second treatment factor.

Physical Activity. At enrollment participants are asked to fill out
questionnaires to assess their health status as well as the habitual level and
timing of activity. The answers will provide the necessary information to
determine the specific personalized implementation if they are randomized to
the physical activity condition. More specifically, in the active treatment
limb, the most intense physical activity that participants report to habitually
maintain for at least half an hour (e.g. (walking, running, cycling) will be
(re)scheduled to be performed daily for half an hour preferably starting three
hours before scheduled bedtime, and never ending closer than two hours prior to
scheduled bedtime. The physical activity will thus at no point exceed the
participants usual amount and intensity, but will be set to a specific time of
the day (evening, between two to three hours before bedtime) and will be
proposed to be performed every day.

Temperature Manipulation. Participants randomized to the temperature condition
are instructed to take a warm bath daily for half an hour preferably starting
three hours before ideal bedtime, and never ending closer than two hours prior
to ideal bedtime. The physical activity and temperature manipulation procedures
will result in elevated skin temperature at bedtime, which can enhance sleep
onset.

Bright Light Treatment. Participants randomized to the bright light treatment
will receive two Philips goLITE BLU light devices (therapy lights). They will
be instructed to install the lights on a table facing a window or lamp to
minimize glare by reducing contrast between the relatively small bright light
source and the background. They will be asked to sit facing the light in close
proximity for half an hour at a fixed time each morning at their earliest
convenience after scheduled wake-up time, for example during breakfast.

Placebo CT. Participants randomized to the placebo treatment will receive a
deactivated Ionizer device. They will be instructed to install the device on a
table where they can sit in close proximity to it for half an hour each morning
at their earliest convenience after ideal wake-up time, for example during
breakfast. This placebo has been applied successfully in several studies in the
USA, but not yet in the Netherlands, making it unlikely to be recognized as a
placebo.

The burden of participating is fitting chronobiological and cognitive
behavioral therapy into daily routine as well as filling out a daily sleep
diary online. Added burden during the assessment weeks (week 1, 6 and 11 of the
protocol) is wearing an accelerometer and filling out some additional
questionnaires (which take an approximately an hour in total).
Benefit of participating is that participant receive chronobiological therapy
and CBT for free.
Ultimately this study develops a clear cut guide line for the treatment of
insomnia, which is beneficial for all insomniacs.