Circadian rhythm in core body temperature and melatonin-levels in spinal cord injury

Core body temperature (CBT) shows circadian rhythmicity with a nadir in the
morning between 4-6 am and a peak 1-4 hours before bedtime. A normal circadian
rhythm is prerequisite for a normal sleep pattern. Individuals with a spinal
cord injury demonstrate a pronounced disturbance in the circadian rhythm of
CBT, whilst this group also frequently reports sleeping problems. The mechanism
behind the altered CBT may relate to the release of melatonin, a hormone that
contributes to a normal sleeping pattern and is produced via neural pathways
that include the central nervous system. No previous study performed a
comprehensive assessment of the release of melatonin and cortisol in spinal
cord-injured individuals and link the endocrine function to the rhythmicity of
CBT.

Our main aim is to describe the 24-h circadian rhythm of skin and core body
temperature in people with SCI and examine whether changes in melatonin and/or
cortisol relate to the altered circadian rhythm in core body temperature
recently described in group.

Observational study

Subjects will wear 8 temperature sensors (4 upper limbs and 4 lower limbs),
ingest a pill to record core body temperature, wear a Sensewear to record
physical activity, and wear a cuff around upper arm for a 24-h blood pressure
recording. In addition, from 6 till 12 PM, subjects are instructed to take a
salivary sample for later analysis of melatonin and cortisol. Experiments will
be performed at home during their normal daily activities. Researchers will
visit participants at home for instruction and instrumentation in the morning
before the test to minimize the burden for the participants.

The intake of this telemetry pill is non-invasive and not dangerous as it can
be swallowed similarly as any medication pill. Our department has extensive
experience with this telemetry system and has been used in previous study
protocols which were approved by the ethics committee (CMO-nr 2007/147,
2007/262, 2008/196, 2008/227, 2009/006, 2009/096, 2009/274, 2010/157). An
ingestion of this pill will also cause no harm to the body and its function due
to the sophisticated elaboration of protection to its surrounding. The pill has
been proved to be reliable and valid for measuring core body temperature at
rest and during exercise, and is now being used and registered at the *Food and
Drug Administration (FDA)* for 21 years. The pill telemetry system has also
been used in SCI subjects in previous studies without any negative side effect.
Important advantages of this system is that it is non-invasive, valid, does not
have the sanitary problems when using different techniques (such as rectal
probes) and can be used without noticing by the subject. From the >35,000 pills
that have been distributed, no negative incidents have been reported. In
addition, the Department of Physiology has experience with >500 subjects that
have used the pill for 1 or multiple day core body temperature measurements. So
far, we have not noticed any negative impact of using the pill in any of the
participants.

The other techniques used in this study (activity monitor, skin temperature,
blood pressure assessment) are techniques that have been used for several years
at the Department of Physiology. None of these measuring techniques are
invasive, painful or possible dangerous for the subject. Using these techniques
will also not influence their daily living.

Participants will be instructed to take hourly salivary samples between 6 and
12 PM for assessment of melatonin and cortisol levels. After a short and simple
explanation, participants will be able to take this salivary sample, which will
be stored for later analysis in our laboratory. This technique is non-invasive
and has no risk for complications. Our collaborators (Prof. G. Atkinson and Dr.
H. Jones, Liverpool John Moores University, United Kingdom) have extensive
experience with this technique (when performed by participants themselves) and
will be involved in setting up and performing this experiment.