To study the acute effect of HD on global and regional CBF.
ID
Source
Brief title
Condition
- Structural brain disorders
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. the change in total and regional CBF during the study session as assessed by
PET-CT scan.
2. the change in rSO2 during the study session as assessed by NIRS, and it's
correlation with the PET-CT scan estimates
Secondary outcome
Change in regional and total CBF correlated to
a. structural cerebral lesions on MRI (e.g. white matter lesions)
b. outcomes of cognitive testing.
Background summary
Hemodialysis (HD) initiation in patients aged >=75 years has doubled the last
decade. Especially in elderly, intradialytic hypotension (IDH) is commonly
observed as a clinical sign of hemodynamic stress. The hemodynamic changes
during HD induce a significant fall in myocardial blood flow that may lead to
cardiac ischemia. Likewise, the hemodynamic stress of HD may affect cerebral
blood flow (CBF) and, if repetitive, may induce cerebral ischemic damage and
may negatively affect cerebral (cognitive) function. Several arguments favor
this pathophysiological hypothesis.
First, cognitive performance in HD patients is best one hour before or one day
after HD and deteriorates during a HD session. Second, long-term blood pressure
variability has been associated with increased risk of cardiovascular events,
stroke, worse cognitive performance, lower hippocampal volume and a risk of
cortical infarcts, in older people independent of the average absolute blood
pressure level. In HD patients, incidences of cerebral ischemia, subclinical
brain damage, cerebral atrophy and cognitive impairment are higher compared to
the general population. Stroke incidence strongly rises in the first month
after HD initiation in elderly patients and remains elevated afterwards
compared with the period before HD was started. This might be related to the
repetitive hemodynamic changes during HD. Third, earlier studies that
investigated CBF in HD patients found that age, anemia, duration of HD therapy
and duration of hypertension are important factors influencing CBF in these
patients. Regional CBF was decreased in the frontal cortex and white matter,
and this was most pronounced in patients with a higher dialysis vintage.
We hypothesize that HD-induced blood pressure changes may lead to a fall in
global and/or regional cerebral blood flow during HD. On the long term, these
repetitive blood pressure changes may cause chronic ischemia, mainly because
cerebral autoregulation that normally preserves the CBF to protect the brain is
likely to be impaired in these patients. Previous studies on the effect of HD
on CBF, using various methods, have yielded conflicting results. [15O]H2O PET
is currently the gold standard to measure CBF. This method has not been used
for the evaluation of CBF during a HD session. Near-infrared spectroscopy
(NIRS) will be used to measure local cerebral tissue regional oxygen saturation
(rSO2). NIRS is an easy method to perform during a HD session and gives
additional information about cerebral oxygen changes during HD, which are
related to CBF.
Study objective
To study the acute effect of HD on global and regional CBF.
Study design
Cross-sectional study.
Study burden and risks
For the combined HD and PET-CT session patients will have to stay in the
hospital for 120 minutes longer than usual for their regular HD treatment. Two
dialysis needles will be inserted in the arterio-venous fistula but these
needles would also have to be inserted without participating in the study. For
the PET-CT scan a peripheral venous catheter will be placed in the
non-arteriovenous fistula arm for administration of [15O]H2O. Each patient will
undergo 3 PET-CT scans of the cerebrum during a single HD session and will
experience the inconvenience of lying in the PET-CT camera for about 50
minutes. The total radiation exposure from radiopharmaceuticals is 3.35 mSv
(3600 MegaBequerel (MBq)) per patient for the total study.
Participating patients will further undergo: 1. A 1.5 Tesla MRI scan; 2. A
bilateral carotid artery duplex echosonography (neurology policlinics); 3. NIRS
during the study session with two self-adhesive pats on the forehead; 4.
Cognitive testing; 5. Blood pressure and heart rate measurement at 30-min
intervals, and immediately before and after each PET-CT scan, which is, in
part, usual care; 6. Arterial blood sampling during the PET-CT study session
will be drawn from the shunt for continuous arterial input during each PET scan
and separate blood will be drawn 3 times for laboratory measurements as part of
usual care. For the continuous arterial input, arterial blood will be sampled
by a dedicated programmable blood-sampler to obtain the radioactivity
concentration in blood during the scan. For all 3 PET scans together the total
arterial blood volume will not exceed 110 ml. For the whole study the total
blood volume will not exceed 150 ml. We believe it is justified to perform the
proposed study in order to elucidate the possible effects of HD on CBF given
the scarcity of data on the background of high stroke rates and an increased
prevalence of cognitive impairment in HD patients, especially in elderly.
Identification of possible changes in (regional) CBF may, first, help to
understand which pathways are involved in the pathophysiology of brain damage
in HD patients that leads to comorbidity and decreased quality of life,
especially in elderly HD patients. Second, this study may help develop dialysis
protocols that better preserve CBF and function. Patients will be informed
regarding accidental findings at the MRI scan or significant asymptomatic
carotid artery stenosis (>70%) that will need medical care.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
Patients aged 65 years or older on maintenance hemodialysis, of which at least 6 patients for a longer period of time (>1years). The patients must have an arteriovenous fistula without recirculation as established by routine Transonic flow measurements. The hemoglobin value should be in the target range 6.2- 8 mmol/l since at least 1 month.
Exclusion criteria
1. The absence of informed consent. 2. Diagnosis of dementia, hydrocephalus, history of raised intracranial pressure, significant (>70%) carotid artery stenosis, end stage liver disease. 3. Actively treated cancer. 4. Actual hospital admission at timing of HD study session. 5. Cochlear implants. 6. Claustrophobia. 7. MRI incompatible implants in the body (including prosthetic heart valves). 8 Pacemakers. 9. Subcutaneous insulin infusion pomp. 10. Any risk of having metal particles in the eyes due to manual work without proper eye protections. 11. Tatoos containing red pigments that form a safety risk. 12. The refusal to be informed of significant carotid artery stenosis (duplex) or structural brain abnormalities (MRI) that could be detected during the study.
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 |
|---|---|
| ClinicalTrials.gov | NCT02272985 |
| CCMO | NL48969.042.14 |