ANZCTR - Registration

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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]

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

Diabetes

Left ventricular hypertrophy

Condition category

Condition code

Neurological

Dementias

Metabolic and Endocrine

Diabetes

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Observational

Patient registry

True

Target follow-up duration

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]

Early Detection / Screening

Comparator / control treatment

Control group without left ventricular hypertrophy

Control group

Active

Outcomes

Primary outcome [1]

Mean changes in brain volume (MRI scan) will be compared between those with and without LVH (echocardiogram)

Timepoint [1]

Baseline, 2 year

Primary outcome [2]

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]

Baseline, 2 year

Secondary outcome [1]

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]

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?

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]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [2]

St Vincent's Hospital (Melbourne) Ltd - Fitzroy

Recruitment postcode(s) [1]

3084 - Heidelberg

Recruitment postcode(s) [2]

3065 - Fitzroy

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council, Australia

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

Research Ethics
Office for Research
Level 8, Harold Stokes Building 
Austin Health
PO Box 5555
Heidelberg
Victoria
Australia 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

23/11/2015

Approval date [1]

24/03/2016

Ethics approval number [1]

HREC/15/Austin/490

Summary

Brief summary

Type 2 diabetes mellitus and dementia are two of the commonest and most disabling conditions worldwide, responsible for an enormous and growing burden of disease. There is increasing awareness that the two conditions are linked, with cognitive impairment (worsening memory, thinking, perception) common in patients type 2 diabetes, and a strong association between type 2 diabetes and Alzheimer’s disease, the most common form of dementia.  Better markers are needed for the prediction of cognitive decline in people with diabetes. Left ventricular hypertrophy (LVH) is an enlargement and thickening (hypertrophy) of the walls of the hearts main pumping chamber, which is common in type 2 diabetes. To date there have been no studies on the association between LVH and cognitive decline in type 2 diabetes. The purpose of this study is to establish whether people with type 2 diabetes and LVH have increased rates of brain volume changes and cognitive impairment. An understanding of whether LVH is contributing to cognitive decline will allow us to identify patients at particular risk.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Amy Brodtmann

Address

The Florey Institute of Neuroscience and Mental Health
Melbourne Brain Centre
245 Burgundy Street
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9035 7004

Fax

+61 3 9035 7301

agbrod@unimelb.edu.au

Contact person for public queries

Name

Sheila Patel

Address

The Florey Institute of Neuroscience and Mental Health
Melbourne Brain Centre
245 Burgundy Street
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9035 7021

Fax

+61 3 9035 7301

skpatel@unimelb.edu.au

Contact person for scientific queries

Name

Amy Brodtmann

Address

The Florey Institute of Neuroscience and Mental Health
Melbourne Brain Centre
245 Burgundy Street
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9035 7004

Fax

+61 3 9035 7301

agbrod@unimelb.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
8419	Study protocol		https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-017-0173-7	skpatel@unimelb.edu.au

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study.	2017	https://dx.doi.org/10.1186/s12902-017-0173-7

N.B. These documents automatically identified may not have been verified by the study sponsor.

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