Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000546459
Ethics application status
Approved
Date submitted
6/04/2016
Date registered
28/04/2016
Date last updated
7/07/2020
Date data sharing statement initially provided
7/07/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
How does heart disease affect cognition and brain structural integrity
in diabetes?
Scientific title
How does cardiovascular disease affect cognition in diabetes? Cardiovascular risk and the
diabetic brain
Secondary ID [1] 288930 0
Nil known
Universal Trial Number (UTN)
U1111-1181-6659
Trial acronym
D2 study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dementia
 298275 0
Diabetes 298276 0
Left ventricular hypertrophy 298304 0
Condition category
Condition code
Neurological 298413 298413 0 0
Dementias
Metabolic and Endocrine 298414 298414 0 0
Diabetes
Cardiovascular 298430 298430 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
2
Target follow-up type
Years
Description of intervention(s) / exposure
This is a single center observational longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes mellitus, 50% with left ventricular hypertophy (LVH, case) and 50% without LVH (control).

Baseline testing will include: demographic and medical history questionnaire, measurement of height, weight, waist and hip, echocardiogram, ECG, carotid ultrasound, 24 hour ambulatory blood pressure monitor, cognitive assessment, magnetic resonance imaging (MRI), physical activity monitor and a blood sample (to determine HbA1c level, APOE genetic risk assessment).

Participants will return for tests at the 2 year time-point.
Intervention code [1] 294401 0
Early Detection / Screening
Comparator / control treatment
Control group without left ventricular hypertrophy
Control group
Active

Outcomes
Primary outcome [1] 297893 0
Mean changes in brain volume (MRI scan) will be compared between those with and without LVH (echocardiogram)
Timepoint [1] 297893 0
Baseline, 2 year
Primary outcome [2] 297894 0
Correlation between brain volume (MRI scan) and cognitive performance (validated paper-and-pencil and computerised cognitive tasks and mood questionnaires) will be compared between those with and without LVH (echocardiogram).

Validated cognitive and mood assessment questionnaire/tests include the following:
a. Patient Health Questionnaire-9 (PHQ-9)
b. Generalised Anxiety Disorder-7 (GAD-7)
c. National Adult Reading Test (NART)
d. Montreal Cognitive Assessment (MoCA)
e. Rey Auditory Verbal Learning Test (RAVLT)
f. Rey Complex Figure (REYCF)
g. Controlled Oral Word Association Test (COWAT)
h. Verbal Fluency Task (VFT)
i. Trail-Making Test (TMT)
j. Digit Span Task from the Weschler Adult Intelligence Scale-Fourth Edition (WAIS-IV)
k. Digit-Symbol Task from the WAIS-IV.
l. Boston Naming Test (BNT)
m. Clock Drawing Task (CDT)
n. Three computerized tests from the CogState Battery
Timepoint [2] 297894 0
Baseline, 2 year
Secondary outcome [1] 322627 0
Correlation between brain volume (MRI scan) and cognitive performance (validated paper-and-pencil and computerised cognitive tasks and mood questionnaires) will be compared between the LVH geometric patterns (echocardiogram; geometric patterns as follows: normal geometry, concentric remodeling, concentric hypertrophy and eccentric hypertrophy),

Validated cognitive and mood assessment questionnaire/tests include the following:
a. Patient Health Questionnaire-9 (PHQ-9)
b. Generalised Anxiety Disorder-7 (GAD-7)
c. National Adult Reading Test (NART)
d. Montreal Cognitive Assessment (MoCA)
e. Rey Auditory Verbal Learning Test (RAVLT)
f. Rey Complex Figure (REYCF)
g. Controlled Oral Word Association Test (COWAT)
h. Verbal Fluency Task (VFT)
i. Trail-Making Test (TMT)
j. Digit Span Task from the Weschler Adult Intelligence Scale-Fourth Edition (WAIS-IV)
k. Digit-Symbol Task from the WAIS-IV.
l. Boston Naming Test (BNT)
m. Clock Drawing Task (CDT)
n. Three computerized tests from the CogState Battery
Timepoint [1] 322627 0
Baseline, 2 year

Eligibility
Key inclusion criteria
1. Diagnosed with type 2 diabetes
2. Aged over 50 years
3. Able to attend 2 study sessions 2 years apart
4. Have no prior neurological or psychiatric disease, including stroke or dementia
5. Can give informed consent and participate in cognitive testing and MRI scans.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known prior stroke or dementia
2. Significant medical co-morbidities making survival for 24 months unlikely
3. Normal exclusion criteria for MRI, e.g. pacemaker, implanted metal, severe claustrophobia
4. Severe diabetic nephropathy, eGFR<30

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
We calculated our sample size in order to include sufficient participant numbers for the primary outcome measures of brain volume and cognitive impairment.. The primary outcome requires a direct comparison of 2 groups: participants with diabetes with and without LVH. We used a modified retrospective case-control method; i.e., all participants have the exposure (diabetes), which will naturally halve by additional risk factor (LVH, expected prevalence around 50%) but only some of them will develop the primary outcome (cognitive impairment). We used an ANCOVA method to estimate sample size for 4 samples (cognitively impaired LVH, non-cognitively impaired LVH, cognitively impaired non-LVH, non-cognitively impaired non-LVH) with repeated measures, including a correlation score between baseline and follow-up. Using alpha=0.05 (two-sided), power=0.8 and an estimated correlation of 0.1, we estimated that 140 (i.e., 35 in each of 4 groups) participants will be required. Given we expect around 20% attrition due to death or non-participation (unable to participate in testing due to new pacemaker/implanted metal/other medical issue, lost to contact, no longer interested), we have estimated a total recruitment number of 168.

By the nature of the study design, the investigators are blinded to the outcome of interest (brain volume loss and cognitive decline at 2 years). MRI image analysis will be performed by an analyst blinded to the case control status. This will be “unblinded” when the cohort is complete and statistical analysis is performed. In addition, we have 2 study “raters”, one who will know details of the patient’s medical history and the other who will be performing cognitive testing and scales of functional status.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/05/2016
Actual
20/05/2016
Date of last participant enrolment
Anticipated
31/05/2020
Actual
Date of last data collection
Anticipated
31/05/2022
Actual
Sample size
Target
168
Accrual to date
150
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5547 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 17030 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 13022 0
3084 - Heidelberg
Recruitment postcode(s) [2] 30699 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 293281 0
Government body
Name [1] 293281 0
National Health and Medical Research Council, Australia
Country [1] 293281 0
Australia
Primary sponsor type
Other
Name
The Florey Institute of Neuroscience and Mental Health
Address
30 Royal Parade (corner Genetics Lane)
Parkville Victoria 3052
Country
Australia
Secondary sponsor category [1] 292104 0
None
Name [1] 292104 0
Address [1] 292104 0
Country [1] 292104 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294774 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 294774 0
Ethics committee country [1] 294774 0
Australia
Date submitted for ethics approval [1] 294774 0
23/11/2015
Approval date [1] 294774 0
24/03/2016
Ethics approval number [1] 294774 0
HREC/15/Austin/490

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

Contacts
Principal investigator
Name 64946 0
Prof Amy Brodtmann
Address 64946 0
The Florey Institute of Neuroscience and Mental Health
Melbourne Brain Centre
245 Burgundy Street
Heidelberg VIC 3084
Country 64946 0
Australia
Phone 64946 0
+61 3 9035 7004
Fax 64946 0
+61 3 9035 7301
Email 64946 0
[email protected]
Contact person for public queries
Name 64947 0
Sheila Patel
Address 64947 0
The Florey Institute of Neuroscience and Mental Health
Melbourne Brain Centre
245 Burgundy Street
Heidelberg VIC 3084
Country 64947 0
Australia
Phone 64947 0
+61 3 9035 7021
Fax 64947 0
+61 3 9035 7301
Email 64947 0
[email protected]
Contact person for scientific queries
Name 64948 0
Amy Brodtmann
Address 64948 0
The Florey Institute of Neuroscience and Mental Health
Melbourne Brain Centre
245 Burgundy Street
Heidelberg VIC 3084
Country 64948 0
Australia
Phone 64948 0
+61 3 9035 7004
Fax 64948 0
+61 3 9035 7301
Email 64948 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
8419Study protocol https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-017-0173-7[email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseDoes left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study.2017https://dx.doi.org/10.1186/s12902-017-0173-7
N.B. These documents automatically identified may not have been verified by the study sponsor.