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Trial registered on ANZCTR


Registration number
ACTRN12616000776404
Ethics application status
Approved
Date submitted
14/05/2016
Date registered
14/06/2016
Date last updated
14/06/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Cognitive function in hemodialysis patients
Scientific title
The impact of inflammation and Autonomic Nervous System activity on cognitive
impairment during a hemodialysis session
Secondary ID [1] 289225 0
None
Universal Trial Number (UTN)
U1111-1182-9346
Trial acronym
ConFun
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Kidney disease patients 298781 0
Cognitive impairment during hemodialysis therapy 298782 0
End stage renal disease patients 298783 0
Condition category
Condition code
Mental Health 298836 298836 0 0
Studies of normal psychology, cognitive function and behaviour
Renal and Urogenital 298907 298907 0 0
Kidney disease

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
4
Target follow-up type
Hours
Description of intervention(s) / exposure
We investigate the effects of inflammation and Autonomic Nervous System activity on cognitive function during a hemodialysis session.All measurements took place 30 min before the onset of the HD therapy and 30 min after the HD therapy. Subjects were studied in a quiet, comfortable room with controlled temperature between 25 and 28 degrees Celcius. Inflammation was evaluated ANS function was assessed simultaneously using pupillometric and Heart Rate Variability (HRV) measurements. A physiologist administered all the methods.
Cognitive function assessment
Cognitive function was assessed before the onset of the HD therapy and 30 min after the completion of the HD therapy. Mini-Mental State Examination (MMSE) in Greek, which includes 11 items and needs about 7-10 minutes to complete, was used for the cognitive impairment evaluation. MMSE evaluates orientation, attention, memory, concentration, language and constructional ability, with a total score range from 0 to 30 which reflects the number of correct responses . Score from 30 to 24 indicates normal cognitive function while score below 24 reflects cognitive impairment, which could be mild (score between 19-24), moderate (score between 10-18) or severe (score below or equal to 9).
Pupillometry
The hand-held infrared pupillometer (NeurOptics PLR-200 trademark City and Country) was used to measure the pupil size and the pupillary light reflex. The pupillometer uses infrared imaging technology and it requires no calibration by the user. Pupillometry was performed on each eye separately. Each eye assessed three times with 5 minutes apart. The pupillometric indices were: 1) maximum pupil size namely the baseline pupil diameter after 2 min dark adaptation, which is an indicator of symaptho-vagal balance, 2) minimum pupil size, which is generally defined as a marker of sympatho-vagal balance, since it is involved in the second segment of the V-shaped pupillometric response, 3) constriction, which is modulated by PNS activity, 4) latency, which is an index of sympatho-vagal balance, 5) average constriction velocity and 6) maximum constriction velocity, which are both sensitive indices of PNS activity , 7) average dilation velocity, which reflects sympatho-vagal balance and 8) 75% pupil size recovery time, which is an index of SNS activity. An average of the three measurements was recorded as the final value.
Inflammation status
The blood samples were collected 30 min before the onset of the HD therapy and 30 min after the completion of the HD therapy. The blood samples were collected in tubes containing EDTA and centrifuged immediately. Serum C-reactive protein (CRP) was detected using the immunonephelometric assay on the BNII nephelometer (N High Sensitivity CRP; Dade Behring Inc, Deerfield, IL).
Intervention code [1] 294758 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298305 0
Change in cognitive function assessed by Mini Mental State Examination questionnaire
Timepoint [1] 298305 0
30 min prior the hemodialysis therapy and 30 minutes following hemodialysis therapy
Primary outcome [2] 298306 0
Autonomic Nervous system activity measured with the method of pupillometry
Timepoint [2] 298306 0
30 min prior the hemodialysis therapy and 30 minutes following hemodialysis therapy
Primary outcome [3] 298379 0
Change in inflammation status assessed by the inflammatory biomarker of C-reactive protein. C-reactive protein was assessed in serum.
Timepoint [3] 298379 0
Increased inflammation due to hemodialysis, 30 min prior the hemodialysis therapy and 30 minutes following hemodialysis therapy
Secondary outcome [1] 323982 0
Association among cognitive impairment assessed using the Mini Mental State Examination questionnaire and inflammation assessed by serum C-reactive protein and Autonomic Nervous System dysfunction which was assessed with the method of pupillometry. It is a composite secondary outcome.
Timepoint [1] 323982 0
30 min prior the hemodialysis therapy and 30 minutes following hemodialysis therapy

Eligibility
Key inclusion criteria
Aged 20 to 60 inclusive, all participants must have been diagnosed with kidney disease and being on HD therapy for 4 hours, 3 times/week for at least six month.
Minimum age
20 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients excluded from the study if they had any of the following criteria: unstable hypertension, congestive heart failure (grade > II according to NYHA), cardiac arrhythmias, anemia, recent myocardial infarction, unstable angina, diabetes mellitus, active liver disease or previous established cause of syncope. Moreover, patients with medications that may affect the cardiovascular or ANS system or pupillary light reflex were excluded from the study.

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis
Two-way Anova with repeated measures. The effect sizes by means of eta squared and the corresponding statistical power (%) after the analysis of the data were also estimated. Linear correlation coefficients (Pearson) were calculated to determine any relations between the variables. In all tests, significance level was set at P<0.05. The effect size of the interaction time group on the outcome measures for Mini Mental State Examination, CRP and pupillometric indexes was 0.10 to 0.26, indicating a small effect, and the corresponding statistical power ranged from 28% to 67%.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7876 0
Greece
State/province [1] 7876 0
Thessaloniki, Macedonia

Funding & Sponsors
Funding source category [1] 293599 0
University
Name [1] 293599 0
Sportmedicine Laboratory, Aristotle University of Thessaloniki
Address [1] 293599 0
Thermi, 47000, Thermi, Thessaloniki, Greece
Country [1] 293599 0
Greece
Primary sponsor type
University
Name
Aristotle University of Thessaloniki
Address
Aristotle University of Thessaloniki
Sportmedicine Laboratory
Thermi, 4700, Thessaloniki, Greece
Country
Greece
Secondary sponsor category [1] 292414 0
None
Name [1] 292414 0
Address [1] 292414 0
Country [1] 292414 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295081 0
Aristotle University of Thessaloniki
Ethics committee address [1] 295081 0
3rd September Str. - University Campus
546 36 THESSALONIKI
Ethics committee country [1] 295081 0
Greece
Date submitted for ethics approval [1] 295081 0
11/03/2016
Approval date [1] 295081 0
01/04/2016
Ethics approval number [1] 295081 0
48279/2016

Summary
Brief summary
Patients with CKD experience many clinical complications and accordingly these complications affect the function of all organ systems of the human body. Cognitive dysfunction and dementia is a common complication found in CKD patients which is profound even in the early stages. Many studies have demonstrated that CKD patients at all stages but especially those in ESRD are at high risk for cognitive dysfunction development and dementia. Indeed, it has been estimated that the prevalence of cognitive impairment in HD patients is around 30-60%.
Reaction time, mental speed, verbal memory, focused concentration; visual scanning and choice reaction time are components of cognitive function, which usually in CKD patients are progressively reduced. Furthermore, inflammation, which is increased in CKD patients and Autonomic Nervous System (ANS) dysfunction, seems to contribute to cognitive impairment in HD patients. It has been supported that inflammation may have a role in the aetiology of mild cognitive impairment. Except from inflammation, there is evidence that ANS dysfunction is associated with mild cognitive function.Thus, the aim of this study was to investigate the impact of inflammation and ANS activity on cognitive function during a HD session.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65878 0
Dr Antonia Kaltsatou
Address 65878 0
University of Thessaly,
School of Physical Education and Sport Science
Karies, 42000, Trikala, Greece
Country 65878 0
Greece
Phone 65878 0
+306938767967
Fax 65878 0
Email 65878 0
akaltsat@gmail.com
Contact person for public queries
Name 65879 0
Prof Evangelia Kouidi
Address 65879 0
Aristotle University of Thessaloniki,
Laboratory of Sportmedicine,
Thermi 57001, Thessaloniki, Greece
Country 65879 0
Greece
Phone 65879 0
+302310992189
Fax 65879 0
Email 65879 0
ekouidi@med.auth.gr
Contact person for scientific queries
Name 65880 0
Prof Asterios Deligiannis
Address 65880 0
Aristotle University of Thessaloniki,
Laboratory of Sportmedicine,
Thermi 57001, Thessaloniki, Greece
Country 65880 0
Greece
Phone 65880 0
+302310992189
Fax 65880 0
+2310992183
Email 65880 0
stergios@med.auth.gr

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary