Developing an effective method of determining circadian phase in humans for clinical applications

Circadian rhythms control the daily cycle of sleep and wake, a disruption of
this control can effect an individual's health. Some treatments, for example
chemotherapy for cancer, appear to be more efficient at a certain phase of the
circadian rhythm of the patient. Unfortunately, despite the growing attention
of these modified treatments, the methods to determine the circadian rhythm of
the patient are not optimal. The standard method to determine circadian phase
in people is the measurement of the timing of the nightly rise of the hormone
melatonin. These measurements cost a lot of money and time and requires
specialist expertise. This research is designed in order to develop a way of
measuring circadian phase of people in an efficient, practical way that is
suitable for use in the clinic. Different methods to determine circadian phase
will be combined and modeled to determine an optimal combination of
measurements, devices and software algorithms to find a system that can be used
by non-circadian researchers to determine the circadian rhythm of a patient for
clinically relevant applications.

The objective of this research is to develop a reliable and efficient method of
determining the phase of the biological (circadian) clock in humans.

In this observational study measurements on working days and free days will be
used to develop algorithms, based on the daily pattern of activity, core body
temperature, light exposure, skin temperature, heart rate frequency and
EEG-derived sleep parameters, comparable to the phase of the individual's
melatonin rhythm. In week 1, activity, skin temperature and heart rate will be
continuous measured. Core body temperature will be measured 2x24h. At the end
of the week, salivary melatonin secretion will be measured in the lab. Week 2
is a rest week. In week 3, there will be two nights of EEG measurements. A
sleep diary will be completed during week 1 and week 3. The wrist activity
meter will be worn on all days that the other sensors are worn and at the same
time a light sensor will be worn around the participant's neck and placed at
the bedside during the sleep period. Before the study begins participants will
complete some questionnaires, further details are given in the protocol.

The burden for the participants during the study consists of the wearing of
lightweight data loggers for a week and two days. Also the completion of the
sleep diary is necessary. Participants do not have to complete questionnaires
or other tasks that would affect their daily functioning. In order to measure
core body temperature a pill needs to be swallowed to obtain the temperature
measurements (for more information see the structure risk analysis in the
protocol). The measurement of skin temperature will be conducted by attaching 6
temperature loggers to the skin (for 7 days). For heart rate measurements, 2
standard ECG electrodes will be attached to the chest (for 7 days). The EEG
measurements will consist of 9 electrodes attached to the head (2
non-consecutive nights). For the activity measurements an accelerometer about
the size of a watch will be worn on the wrist (for 7 days). The light sensor is
the size of a USB stick and will be worn around the participant's neck (at the
same time as the accelerometer is worn on the wrist). Also, 8 saliva samples
will be taken (1 an hour) one night in the laboratory, beginning 7h before
habitual sleep onset. Participants have the option of sleeping in the facility
so that their sleep onset will not be altered.