Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial registered on ANZCTR
Registration number
ACTRN12618000496213
Ethics application status
Approved
Date submitted
16/03/2018
Date registered
5/04/2018
Date last updated
17/02/2020
Date data sharing statement initially provided
11/03/2019
Date results information initially provided
17/02/2020
Type of registration
Prospectively registered
Titles & IDs
Public title
Is dysfunction of brain blood vessels associated with cognitive impairment in type-1 diabetes?
Query!
Scientific title
Is dysfunction of brain blood vessels associated with cognitive impairment in type-1 diabetes?
Query!
Secondary ID [1]
294176
0
None
Query!
Universal Trial Number (UTN)
U1111-1209-9447
Query!
Trial acronym
iNeuroT1D
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes Mellitus
306805
0
Query!
Condition category
Condition code
Metabolic and Endocrine
305915
305915
0
0
Query!
Diabetes
Query!
Mental Health
306209
306209
0
0
Query!
Studies of normal psychology, cognitive function and behaviour
Query!
Intervention/exposure
Study type
Observational
Query!
Patient registry
False
Query!
Target follow-up duration
Query!
Target follow-up type
Query!
Description of intervention(s) / exposure
A pilot cross-sectional study involving Type 1 Diabetic (T1D) adults and age-matched non-diabetic controls will be conducted over two visits scheduled up to seven days apart.
Anthropometric measurements of height, weight and waist circumference will then be obtained prior to clinic Blood Pressure (BP) and arterial compliance (AC) measurements. We will obtain a finger-prick glucose reading from T1D to ensure that their blood glucose levels are at least 6.5mmol/L before proceeding with the rest of the assessments.
Participants will then be fitted with a headpiece with two ultrasound probes on both sides of the temporal region. This transcranial doppler (TCD) device will monitor the blood flow velocity in either the middle cerebral artery or the anterior cerebral artery. Participants will have their cerebral blood flow velocity recorded at rest. Participants will then perform a series of cognitive tasks continuously for approximately 70 mins, whilst the TCD device records changes in blood flow velocities. The neuropsychological test battery will consist of the Trail Making Task, the N-back task, Rey-Osterrieth complex figure, and the NIH Toolbox Battery of cognitive function.
Volunteers will arrive for the second visit and a blood sample will be obtained. They will complete paper-based questionnaires that will measure various subjective perceptions of their current mood states using the Profile of Mood States (POMS) Questionnaire and the Center for Epidemiological Studies Depression Scale (CES-D) and diabetes self-care. Volunteers will then proceed to do a 10-min auditory function test, the NIH Toolbox 9-hole Pegboard Dexterity test, and the Addenbrooke’s Cognitive Examination-III (a measure of global cognitive status) (ACE-III).
Query!
Intervention code [1]
300470
0
Not applicable
Query!
Comparator / control treatment
Adults with no diabetes
Query!
Control group
Active
Query!
Outcomes
Primary outcome [1]
304950
0
Composite Primary Outcome: Overall performance of a neuropsychological test battery, consisting of the Trail Making Task, the N-back task, Rey-Osterrieth complex figure, and the NIH Toolbox Battery of cognitive function.
Query!
Assessment method [1]
304950
0
Query!
Timepoint [1]
304950
0
Week 0 visit 1
Query!
Secondary outcome [1]
343687
0
Clinic blood pressure assessed by sphygmomanometry.
Query!
Assessment method [1]
343687
0
Query!
Timepoint [1]
343687
0
Week 0, visit 1.
Query!
Secondary outcome [2]
343689
0
Cerebral arterial compliance assessed by TCD ultrasound.
Query!
Assessment method [2]
343689
0
Query!
Timepoint [2]
343689
0
Week 0, visit 1.
Query!
Secondary outcome [3]
343690
0
Cerebrovascular responsiveness (CVR) to hypercapnia assessed by TCD ultrasound.
Query!
Assessment method [3]
343690
0
Query!
Timepoint [3]
343690
0
Week 0, visit 1.
Query!
Secondary outcome [4]
343692
0
Neurovascular coupling (cerebrovascular responsiveness to cognitive stimuli) assessed by TCD ultrasound
Query!
Assessment method [4]
343692
0
Query!
Timepoint [4]
343692
0
Week 0, visit 1.
Query!
Secondary outcome [5]
343693
0
Composite secondary outcome: Individual test performance. Performance on a neuropsychological test battery, assessing executive function, working memory, processing speed, memory and psychomotor speed of the cognitive domain using the Trail Making Task, the N-back task, Rey-Osterrieth complex figure, and the NIH Toolbox Battery of cognitive function.
Query!
Assessment method [5]
343693
0
Query!
Timepoint [5]
343693
0
Week 0, visit 1
Query!
Secondary outcome [6]
343695
0
Manual dexterity (psychomotor speed), measured using the NIH Toolbox 9-hole Pegboard Dexterity test.
Query!
Assessment method [6]
343695
0
Query!
Timepoint [6]
343695
0
Week 0, visit 2.
Query!
Secondary outcome [7]
343696
0
Central auditory processing function, assessed using iPad and headphones, using the "words-in-noise" test.
Query!
Assessment method [7]
343696
0
Query!
Timepoint [7]
343696
0
Week 0, visit 2
Query!
Secondary outcome [8]
343699
0
Composite secondary outcome: Mood assessed using the Profile of Mood States (POMS) Questionnaire and the Center for Epidemiological Studies Depression Scale (CES-D).
Query!
Assessment method [8]
343699
0
Query!
Timepoint [8]
343699
0
Week 0, visit 2.
Query!
Secondary outcome [9]
343700
0
Diabetes self-care, assessed using a 16-question questionnaire: the Diabetes Self-Management Questionnaire (DSMQ), designed to assess behaviours associated with metabolic control in common treatment regimes for T1D and T2D in adult patients.
Query!
Assessment method [9]
343700
0
Query!
Timepoint [9]
343700
0
Week 0, visit 2.
Query!
Secondary outcome [10]
343701
0
Cardiometabolic biomarkers (HbA1C; lipids; inflammatory biomarkers such as IL-1b, IL-6, IL-8, IL-10, IL-12A/B and TNF-a), assessed by plasma assay.
Query!
Assessment method [10]
343701
0
Query!
Timepoint [10]
343701
0
Week 0, visit 2.
Query!
Secondary outcome [11]
343702
0
S100ß (marker of blood-brain-barrier integrity), assessed by plasma assay.
Query!
Assessment method [11]
343702
0
Query!
Timepoint [11]
343702
0
Week 0, visit 2.
Query!
Eligibility
Key inclusion criteria
Inclusion criteria for T1D:
Age 30 – 80 years old
T1D diagnosed before 18 years of age
No advanced diabetes complications such as blindness or deafness
Not hospitalised for severe glycemic events in the last 3 months
Inclusion criteria for control group:
No T1D or T2D diagnosis and HbA1c <6.5%
Not taking medication for hypertension and cholesterol
Query!
Minimum age
30
Years
Query!
Query!
Maximum age
80
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
Yes
Query!
Key exclusion criteria
Not fluent in reading and writing in English
No detectable transcranial Doppler (TCD) ultrasound signal in the middle cerebral artery on either side.
Liver or kidney disease
Malignant cancer
Excessive alcohol intake (>15 drinks per week)
Pregnancy
Neurological conditions including stroke, TIA, major depression, multiple sclerosis, Parkinson’s disease or dementia or mild cognitive impairment.
Unwilling to provide a blood sample
Query!
Study design
Purpose
Natural history
Query!
Duration
Cross-sectional
Query!
Selection
Defined population
Query!
Timing
Prospective
Query!
Statistical methods / analysis
Independent t-tests will be used to compare group differences in each of the following: basal cerebral hemodynamics (PI, RI, CVRi and mean blood flow velocity), CVR to hypercapnia, CVR to the cognitive test battery (neurovascular coupling capacity), performance on each of the individual cognitive tests, auditory function and overall performance to the test battery. Associations between cerebrovascular function, cognitive function, auditory function participant characteristics and markers of diabetes including disease duration, metabolic profile, glycaemic fluctuations, self-care and inflammatory cytokines will be examined using correlation coefficient analyses and Bayesian analysis. Covariates such as age, gender and pre-test glucose levels will be included when appropriate. Adjustment for multiple comparisons will also be made.
Query!
Recruitment
Recruitment status
Completed
Query!
Date of first participant enrolment
Anticipated
1/05/2018
Query!
Actual
10/07/2018
Query!
Date of last participant enrolment
Anticipated
24/05/2019
Query!
Actual
13/12/2019
Query!
Date of last data collection
Anticipated
31/05/2019
Query!
Actual
13/12/2019
Query!
Sample size
Target
50
Query!
Accrual to date
Query!
Final
40
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment postcode(s) [1]
21888
0
2300 - Newcastle
Query!
Funding & Sponsors
Funding source category [1]
298809
0
Other Collaborative groups
Query!
Name [1]
298809
0
Hunter Medical Research Institute – Keith Tulloch Wines Project Grant
Query!
Address [1]
298809
0
Lot 1 Kookaburra Circuit, New Lambton Heights, NSW, 2305
Query!
Country [1]
298809
0
Australia
Query!
Primary sponsor type
University
Query!
Name
University of Newcastle
Query!
Address
University of Newcastle
Faculty of Health and Medicine
School of Biomedical Sciences & Pharmacy
Clinical Nutrition Research Centre
University Drive
Callaghan, New South Wales 2308
Query!
Country
Australia
Query!
Secondary sponsor category [1]
298007
0
None
Query!
Name [1]
298007
0
Query!
Address [1]
298007
0
Query!
Country [1]
298007
0
Query!
Other collaborator category [1]
279965
0
University
Query!
Name [1]
279965
0
Curtin University
Query!
Address [1]
279965
0
Curtin University
Curtin Health Innovation Research Institute
School of Public Health
Kent Street
Bentley WA 6102
Query!
Country [1]
279965
0
Australia
Query!
Ethics approval
Ethics application status
Approved
Query!
Ethics committee name [1]
299756
0
University of Newcastle Human Research Ethics Committee
Query!
Ethics committee address [1]
299756
0
Research & Innovation Services
Research Integrity Unit
The University of Newcastle
University Drive
Callaghan NSW 2308
Query!
Ethics committee country [1]
299756
0
Query!
Date submitted for ethics approval [1]
299756
0
02/02/2018
Query!
Approval date [1]
299756
0
30/04/2018
Query!
Ethics approval number [1]
299756
0
H-2018-0038
Query!
Summary
Brief summary
To date, almost all large neurocognitive studies of type 1 diabetes (T1D) have focused on paediatric groups, as compared to most type 2 diabetes (T2D) studies which focus on old age. Early onset diabetes has severe impacts on the neurocognitive development of children and adolescents with T1D, particularly in learning and memory skills. This deficit is accompanied by atrophic changes in the medial prefrontal regions that are known to be rapidly developing in children. While there is a plethora of literature linking T2D with greater risk of dementia, little is known about the role of metabolic and vascular factors on the ageing brain in adults with T1D. One retrospective study has shown that elderly adults with T1D are 83% more likely to get dementia compared to a 50% greater risk in T2D than in non-diabetic adults. However, the frequent presence of comorbidities in older diabetic adults further complicates the underlying mechanism of accelerated brain ageing in T1D.
A postulated underlying mechanism of T1D-related cognitive decline is endothelial dysfunction in the cerebral microvasculature caused by pro-inflammatory cytokines associated with the disease and advanced glycation end-products (AGE) due to hyperglycaemia.
We have shown significant cerebral arterial stiffness (20%) in elderly T2D adults compared to non-diabetics, which is linked to poorer perfusion and performance during cognitive testing. Structural and functional changes of the cerebral vasculature is already evident in young T1D adults (mean age of 32 years) where a significant 20% reduction in cerebral vasodilator responsiveness to a hypercapnic challenge was seen compared to non-diabetic controls. The authors also reported significant stiffening of the carotid arteries that is independent of the presence of hyperlipidaemia. It seems that despite the arduous therapy of multiple insulin injections daily, this does not prevent the occurrence of serious late-arising complications including kidney failure, blindness and widespread cardiovascular disease in T1D.
Given that diabetes is a systemic disease, it is plausible that multiple organs including the auditory system are also affected; yet little attention has been given to preserving auditory function in diabetes.
Age-related neurodegeneration of different cortical areas and/or cognitive impairment may also affect central auditory function. Central auditory dysfunction is hypothesised to occur before objective cognitive tests become abnormal. There is no study evaluating the link between cerebrovascular dysfunction and cognitive impairment and central auditory dysfunction in T1D. We hypothesise that T1D adults have cerebrovascular dysfunction and elevated inflammation, mediated by glycation of the endothelium, which will negatively impact their cognitive and auditory function.
Query!
Trial website
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
81470
0
Dr Rachel Wong
Query!
Address
81470
0
University of Newcastle
Faculty of Health and Medicine
School of Biomedical Sciences & Pharmacy
Clinical Nutrition Research Centre
University Drive
Callaghan, New South Wales 2308
Query!
Country
81470
0
Australia
Query!
Phone
81470
0
+61 2 4921 6408
Query!
Fax
81470
0
Query!
Email
81470
0
[email protected]
Query!
Contact person for public queries
Name
81471
0
Dr Rachel Wong
Query!
Address
81471
0
University of Newcastle
Faculty of Health and Medicine
School of Biomedical Sciences & Pharmacy
Clinical Nutrition Research Centre
University Ring Road
Callaghan, New South Wales 2308
Query!
Country
81471
0
Australia
Query!
Phone
81471
0
+61 2 4921 6408
Query!
Fax
81471
0
Query!
Email
81471
0
[email protected]
Query!
Contact person for scientific queries
Name
81472
0
Dr Rachel Wong
Query!
Address
81472
0
University of Newcastle
Faculty of Health and Medicine
School of Biomedical Sciences & Pharmacy
Clinical Nutrition Research Centre
University Ring Road
Callaghan, New South Wales 2308
Query!
Country
81472
0
Australia
Query!
Phone
81472
0
+61 2 4921 6408
Query!
Fax
81472
0
Query!
Email
81472
0
[email protected]
Query!
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Study is de-identified
Query!
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
No additional documents have been identified.
Download to PDF