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Trial registered on ANZCTR


Registration number
ACTRN12616001409460
Ethics application status
Approved
Date submitted
7/12/2015
Date registered
10/10/2016
Date last updated
10/10/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Influence of Diabetes on Retinal Vessels
Scientific title
Functional Abnormalities of Retinal Blood Vessels are Related to Blood Factors in Patients with Type 1 Diabetes
Secondary ID [1] 289224 0
none
Universal Trial Number (UTN)
U1111-1177-3277
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
diabetes 296951 0
retinal vascular changes 298780 0
Condition category
Condition code
Metabolic and Endocrine 297194 297194 0 0
Diabetes
Eye 297600 297600 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All procedures and measurements in 41 patients with diabetes type 1 were made by one doctor of medicine in the ophthalmic clinic from 9.00 to 12.00 o’clock. Patients were treated only once in the study.

The conversation about diabetes, arterial hypertension, dyslipidemia, other diseases and their treatment was made. Medical documentation about diabetes was checked. The corrected visual acuity, visual field by static perimetry and intraocular pressure by non-contact tonometer were measured. Examinations with slit-lamp of anterior and posterior pars of the eye were performed. The body weight and height were measured and body mass index was calculated. Measurements of blood pressure were made on the left arm.

The evaluation of functional features of retinal blood vessels in patients with diabetes type 1 was made by:
1. calculation of central retina artery (CRAE) and vein equivalent (CRVE) obtained from measurements of the internal diameters of the retinal blood vessels from the retinal images
2. measurement of mean velocity (MV) in central retinal artery in the optic nerve by Doppler ultrasound device
3. measurement of volume and blood flow in retinal vessels thinner than 30 micrometres by Scanning laser Doppler flowmeter

Those three sets of measurements were made in basal conditions and during 8 Hz retinal flickering light stimulation of the eye. Index of mean velocity in the central retinal artery, indexes of volume and blood flow in small retinal vessels and vasodilatation indexes of central retina artery and vein equivalents were calculated from measurements in basal conditions and during light stimulation.

8Hz white pulse light of the time length of 50 ms was used as physiological retinal stimulator. A halogen lamp with a power of 150 watts and 2,500 candelas was built in the special device with which it was possible to regulate the frequency and intensity of light. The colour spectrum of the halogen lamp ranged from 400 to 2500 nm. Distance of the lamp to the eye was 40 centimetres. The lamp was set at 90 degrees to the visual axis of the eye being measured. Between the lamp and the eye prism was placed at an angle of 45 degrees where the intensity of the light reduced for 30.3% to the final luminance of 4800 lux. In each participant one eye was exposed for 45 seconds to 8 Hz flickering light stimulation, after which three repeated measurements with all three devices were made with continued irritation.

Blood was taken on an empty stomach in the morning from 8.00 to 10.00 o’clock from the vein in the left arm. It was frozen on -20.0 C and waited for biochemical tests.
Intervention code [1] 293704 0
Early detection / Screening
Comparator / control treatment
All procedures and measurements in 37 representatives of the healthy control group (one case with treated hypertension) without diabetes were made by one doctor of medicine in the ophthalmic clinic from 9.00 to 12.00 o’clock. Individuals from the control group were treated only once in the study.

The conversation about arterial hypertension, dyslipidemia, other diseases and their treatment was made. The corrected visual acuity, visual field by static perimetry and intraocular pressure by non-contact tonometer were measured. Examinations with slit-lamp of anterior and posterior pars of the eye were performed. The body weight and height were measured and body mass index was calculated. Measurements of blood pressure were made on the left arm.

The evaluation of functional features of retinal blood vessels in the control group was made by:
1. calculation of central retina artery (CRAE) and vein equivalent (CRVE) obtained from measurements of the internal diameters of the retinal blood vessels from the retinal images
2. measurement of mean velocity (MV) in central retinal artery in the optic nerve by Doppler ultrasound device
3. measurement of volume and blood flow in retinal vessels thinner than 30 micrometres by Scanning laser Doppler flowmeter

Those three sets of measurements were made in basal conditions and during 8 Hz retinal flickering light stimulation of the eye. All indexes of vasodilatation were calculated like in patient group.

Blood was taken on an empty stomach in the morning from 8.00 to 10.00 o’clock from the vein in the left arm. It was frozen on -20.0 C and waited for biochemical tests.
Control group
Active

Outcomes
Primary outcome [1] 299445 0
Mean central retinal artery equivalent (CRAE), assessed by retinal imaging.
Timepoint [1] 299445 0
At baseline and 45 secods into retinal flickering light stimulation.
Primary outcome [2] 299446 0
Mean blood flow in the small retinal vessels, assessed using scanning laser Doppler flowmeter.
Timepoint [2] 299446 0
At baseline and 45 secods into retinal flickering light stimulation.
Primary outcome [3] 299448 0
Mean blood flow velocity in the central retinal artery, assessed using Doppler ultrasound device.
Timepoint [3] 299448 0
At baseline and 45 secods into retinal flickering light stimulation.
Secondary outcome [1] 327189 0
Mean serum glucose concentration.
Timepoint [1] 327189 0
There is a single assessment timepoint only in each participant
Secondary outcome [2] 327190 0
Mean serum fructosamine concentration.
Timepoint [2] 327190 0
There is a single assessment timepoint only in each participant
Secondary outcome [3] 327191 0
Mean serum 8-OHdG concentration.
Timepoint [3] 327191 0
There is a single assessment timepoint only in each participant
Secondary outcome [4] 327192 0
Mean serum IL-6 concentration.
Timepoint [4] 327192 0
There is a single assessment timepoint only in each participant
Secondary outcome [5] 327193 0
Mean serum hs-CRP concentration.
Timepoint [5] 327193 0
There is a single assessment timepoint only in each participant
Secondary outcome [6] 327196 0
Mean serum NOx concentration.
Timepoint [6] 327196 0
There is a single assessment timepoint only in each participant
Secondary outcome [7] 327197 0
Mean serum ADMA concentration.
Timepoint [7] 327197 0
There is a single assessment timepoint only in each participant
Secondary outcome [8] 327198 0
Mean serum VCAM-1 concentration.
Timepoint [8] 327198 0
There is a single assessment timepoint only in each participant
Secondary outcome [9] 327199 0
Mean serum triglycerides concentration.
Timepoint [9] 327199 0
There is a single assessment timepoint only in each participant.
Secondary outcome [10] 327823 0
Mean serum cholesterol concentration.
Timepoint [10] 327823 0
There is a single assessment timepoint only in each participant.
Secondary outcome [11] 327824 0
Mean serum LDL concentration.
Timepoint [11] 327824 0
There is a single assessment timepoint only in each participant.
Secondary outcome [12] 327825 0
Mean serum HDL concentration.
Timepoint [12] 327825 0
There is a single assessment timepoint only in each participant.
Secondary outcome [13] 327826 0
Mean central retinal vein equivalent (CRVE), assessed by retinal imaging.
Timepoint [13] 327826 0
At baseline and 45 secods into retinal flickering light stimulation.
Secondary outcome [14] 327827 0
Mean blood volume in the small retinal vessels, assessed using scanning laser Doppler flowmeter.
Timepoint [14] 327827 0
At baseline and 45 secods into retinal flickering light stimulation.

Eligibility
Key inclusion criteria
Patients with type 1 diabetes:
treatment with insulin
normal blood pressure and concentration of blood lipids
the use up to 10 cigarettes per day
visual acuity more then 0.9 with correction
intraocular pressure up to 21 mmHg
clear optical media


Control group:
normal blood pressure and concentration of blood lipids
the use up to 10 cigarettes per day
visual acuity more then 0.9 with correction
intraocular pressure up to 21 mmHg
clear optical media

Minimum age
18 Years
Maximum age
42 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Patients with type 1 diabetes:
diabetic retinopathy
glaucoma
other retinal and optic nerve diseases which affect the results of the study

Control group:
diabetes
glaucoma
other retinal and optic nerve diseases which affect the results of the study

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
The test sample size of ten participants with diabetes and ten without it was assembled.

The glucose concentration in 10 participants of the control group was 4.90 +/- 2.99 mmol/L and in 10 participants of the type 1 diabetes group was 6.23 mmol/L. Taking into account the power 0.8 and statistical significance level of 0.05 sample size of 80 was calculated.

The index of CRAE in 10 participants of the control group was 1.035 +/- 0.025 and in 10 participants of the type 1 diabetes group was 1.023. Taking into account the power 0.8 and statistical significance level of 0.05 sample size of 68 was calculated.

The final size of 78 participants in both groups was defined by the observation of statistically significant difference in vasodilatation index of central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE), blood flow, volume and velocity index and mean velocity (MV) index in the central retinal artery (CRA) between both groups. It was determined by finding out statistically significant interdependence between that values and the level of glucose, fructosamine, 8-hydroxy-2' -deoxyguanosine (8-OHdG), interleukin 1 (IL-6) and high-sensitivity C-reactive protein (hs-CRP).

The Shapiro-Wilk test is used to test the distribution of normality.
The difference in the incidence of attributive parameters between the two groups of subjects are calculated by chi square test.
For numeric variables are to determine the differences between them using a two-way Student's t-test.
The independent two-sample t-test and the Pearson product moment correlation coefficient are used for the parametric variables, whereas the Mann-Whitney U-Test and Spearman's rank correlation coefficient are used for the nonparametric variables.
The repeatability of the measurements is confirmed with a coefficient of variation.
Multiple linear regression determine the independent impact of the predictive variables
The criterion of statistical significance was P < 0.05.

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] 7397 0
Slovenia
State/province [1] 7397 0
Ljubljana

Funding & Sponsors
Funding source category [1] 294400 0
Hospital
Name [1] 294400 0
Research tertiary projects in University Medical Centre in Ljubljana
Country [1] 294400 0
Slovenia
Funding source category [2] 294402 0
Hospital
Name [2] 294402 0
Institute of Clinical Chemistry and Biochemistry, University Medical Centre in Ljubljana
Country [2] 294402 0
Slovenia
Primary sponsor type
Individual
Name
Debelic Vladimir
Address
Eye Clinic
University Medical Centre in Ljubljana
Grabloviceva 46
1000 Ljubljana
Slovenia
Europe
Country
Slovenia
Secondary sponsor category [1] 293248 0
Hospital
Name [1] 293248 0
Institute of Clinical Chemistry and Biochemistry, University Medical Centre in Ljubljana
Address [1] 293248 0
Institute of Clinical Chemistry and Biochemistry
University Medical Centre in Ljubljana
Njegoseva 4
1000 Ljubljana
Slovenia
Europe
Country [1] 293248 0
Slovenia
Secondary sponsor category [2] 293249 0
Individual
Name [2] 293249 0
Drnovsek Olup Brigita
Address [2] 293249 0
Eye Clinic
University Medical Centre in Ljubljana
Grabloviceva 46
1000 Ljubljana
Slovenia
Europe
Country [2] 293249 0
Slovenia
Secondary sponsor category [3] 293250 0
Individual
Name [3] 293250 0
Zizek Bogomir
Address [3] 293250 0
Faculty of Health Sciences
University of Ljubljana
Zdravstvena pot 5
1000 Ljubljana
Slovenia
Europe
Country [3] 293250 0
Slovenia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293989 0
Medical Ethics Committee of the Republic of Slovenia
Ethics committee address [1] 293989 0
Ethics committee country [1] 293989 0
Slovenia
Date submitted for ethics approval [1] 293989 0
18/10/2006
Approval date [1] 293989 0
13/02/2007
Ethics approval number [1] 293989 0
38/02/07

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62014 0
Dr Debelic Vladimir
Address 62014 0
Eye Hospital
University Medical Centre in Ljubljana
Grabloviceva 46
1000 Ljubljana
Slovenia
Europe
Country 62014 0
Slovenia
Phone 62014 0
+386 40 567 614
Fax 62014 0
+386 1 522 19 60
Email 62014 0
Contact person for public queries
Name 62015 0
Drnovsek Olup Brigita
Address 62015 0
Eye Hospital
University Medical Centre in Ljubljana
Grabloviceva 46
1000 Ljubljana
Slovenia
Europe
Country 62015 0
Slovenia
Phone 62015 0
+386 1 522 1900
Fax 62015 0
+386 40 567 614
Email 62015 0
Contact person for scientific queries
Name 62016 0
Zizek Bogomir
Address 62016 0
Faculty of Health Sciences
University of Ljubljana
Zdravstvena pot 5
1000 Ljubljana
Slovenia
Europe
Country 62016 0
Slovenia
Phone 62016 0
+386 1 300 11 11
Fax 62016 0
+386 1 300 11 19
Email 62016 0

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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