This study aims at understanding the circadian disruption in chronic hemodialysis patients and provide a molecular basis for the etiology of sleep-wake cycle disturbances. The hypothesis that the circadian clock is disturbed in chronic hemodialysis…
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Establish 24-hr peripheral clock gene and clock controlled output gene
expression profiles in blood of chronic hemodialysis patients compared to
control subjects to diagnose renal disease mediated circadian disruption.
Secondary outcome
1. Investigate the clock synchronization and phase-shifting potential of serum
from chronic kidney disease patient and control groups. Renal patients are
expected to have high levels of clock resetting compounds.
2. Determine the correlation between clock gene expression and a physiogical
read-out (sleep).
Background summary
A disruption of the biological clock is presumed in chronic hemodialysis
patients since they frequently suffer from sleep problems, frequently show a
non-dipper blood pressure profile and lack a nocturnal melatonin surge, which
is a reasonable readout for disturbed clock performance. The origin of these
clinically observed disturbances is still unknown. Possibly, there is an
underlying disturbed peripheral clock synchronization by constitutively high
(rather than oscillating) amounts of humoral clock-resetting compounds.
Study objective
This study aims at understanding the circadian disruption in chronic
hemodialysis patients and provide a molecular basis for the etiology of
sleep-wake cycle disturbances. The hypothesis that the circadian clock is
disturbed in chronic hemodialysis patients is tested. Two questions will be
addressed:
1. is renal failure associated to altered peripheral circadian expression of
clock genes and clock-controlled genes in chronic hemodialysis patients
compared to matched control subjects with normal kidney function and
2. is a constitutively increased level of clock resetting compounds in serum of
chronic hemodialysis patients responsible for the disturbed circadian
expression. Presumably certain compounds in HD-patients are continuously
available exceeding threshold values, in comparison to lower and cyclically
levels available in subjects with normal kidney function (including patients
with and without disturbed sleep).
The outcome of these experiments will shed new light on treatment options,
development of disease and optimizing chronopharmacology in patients with
chronic kidney disease.
Study design
observational study
Study burden and risks
Hospitalized chronic hemodialysis patients with and without reported sleeping
problems and their matched control subjects are asked to participate in the
following:
- 7 blood samples taken in PAXgene tubes to collect blood and stabilize
intracellular RNA (9.00, 13.00, 17.00, 21.00, 1.00, 5.00, 9.00) (HD patients
and control subjects)
- 7 serum samples taken at 9.00, 13.00, 17.00, 21.00, 1.00, 5.00, 9.00 (HD
patients and control subjects)
- 2 serum samples + hemodialysis bath water samples taken in standard
collection tubes (before and after dialysis) (HD patients only)
- Epworth Sleepiness Scale (short sleepiness questionnaire) (HD and control
patients)
- Chronotype questionnaire: Ochtend-/avondtype vragenlijst (HD patients and
control subjects)
- Medication record (HD patients and control subjects)
- Registration of meal time + type of meal + coffee intake (HD patients and
control subjects)
- 4 days of objective sleep measurements by actigraphy (HD patients and control
subjects)
Participants don*t receive direct benefit from participation in the study. The
collected data help to understand the circadian clock problems in chronic
hemodialysis patients. In the future this can possibly be used to define
therapeutic targets, optimize dialysis schedules or develop
chronopharmacotherapy.
Postbus 1502
3800 BM Amersfoort
NL
Postbus 1502
3800 BM Amersfoort
NL
Listed location countries
Age
Inclusion criteria
Chronic hemodialysis patients:
- Hospitalized, stable chronic hemodialysis patients
- Written informed consent
- Age 18-85 years
- Good understanding of Dutch language;Control patients:
- Hospitalized, stable patients
- MDRD-GFR > 60 ml/min
- Age and gender matched with hemodialysis patient
- Written informed consent
- Age 18-85 years
- Good understanding of Dutch language
Exclusion criteria
- Blindness
- Fever
- CRP > 20 mg/L
- Diabetes
- Serious co-morbidity that prevents participation in this study according to the investigators (e.g. neurological, psychiatric, angina, heart failure NYHA class IV)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL39856.100.12 |