ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12614000222640

Ethics application status

Approved

Date submitted

20/02/2014

Date registered

3/03/2014

Date last updated

4/06/2019

Date data sharing statement initially provided

4/06/2019

Date results information initially provided

4/06/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Cognition and Type 2 Diabetes – A pilot randomised controlled trial (RCT) of exercise

Scientific title

In people with type 2 diabetes, does structured exercise improve or preserve brain health?

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1153-6018

Trial acronym

CDOT-X

Linked study record

Health condition

Health condition(s) or problem(s) studied:

cognitive impairment

dementia

type 2 diabetes

Condition category

Condition code

Neurological

Dementias

Physical Medicine / Rehabilitation

Other physical medicine / rehabilitation

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The intervention group will receive a 6 month structured exercise program by fully trained exercise physiologists. Two one-hour supervised sessions per week will occur at the Menzies Research Institute gymnasium on non-consecutive days, plus a further one-hour per week unsupervised session at the participant’s home with prescribed exercises (e.g. walking). Each supervised session will consist of a warm-up and cool-down, moderate- to high-intensity progressive resistance training exercises using body weight, simple machine or free weights of 8-15 repetitions (e.g. free weights: bicep curls, shoulder press, chest press; body weight: step ups or sit to stand +/- weight vest; machine weights: quadriceps press, shoulder press, chest press, knee extension), and an aerobic component involving stationary cycling, cross trainer or treadmill walking at 40-84% of VO2R. The program will be tailored to participant’s abilities and progressive intensity applied with increasing fitness. Adherence will be assessed by attendance at the supervised exercise sessions and completion of personal exercise diaries.

Intervention code [1]

Treatment: Other

Intervention code [2]

Lifestyle

Comparator / control treatment

The control arm will also receive a 6 month light stretching/gentle movements program. Two one-hour supervised sessions per week will occur at the Menzies Research Institute, and the participants will be asked to carry out one unsupervised session at home. Each session will consist of gentle stretches and movements of the upper and lower limb muscles. Adherence will be assessed by attendance at the supervised exercise sessions and completion of personal exercise diaries.

Control group

Active

Outcomes

Primary outcome [1]

Brain MRI - grey matter volume

Timepoint [1]

baseline and 6 months

Secondary outcome [1]

Brain MRI – Measures of interest are brain volumes (white, white matter lesion, hippocampus), regional cerebral perfusion (CBF using arterial spin labeling ASL), white matter integrity (fractional anisotropy FA, mean diffusivity MD using diffusion tensor imaging DTI).

Timepoint [1]

Baseline and 6 months

Secondary outcome [2]

Cognitive measures: assessments of selective attention, executive function, processing speed and memory will be made using standard neurological tests:Hopkins Verbal Learning Test – R, Form 1; Wechsler Adult Intelligence Scale – Third Edition (WAIS-III) Subsets of Digit Span, Digit Symbol Coding and Symbol Search; Controlled Oral Word Association Test (COWAT); Category Fluency Test; Rey Complex Figure copying and delayed recall task; Stroop Test (Victoria Form);Trails A & B.

Timepoint [2]

Baseline and 6 months

Secondary outcome [3]

Central haemodynamics: These will be measured non-invasively at rest, during exercise VO2 test and over 24 hours

Timepoint [3]

Secondary outcome [4]

Retinal photography using a Canon CR-DGi non-mydriatic retinal camera– retinal vascular measures (length/diameter, optimality ratio)

Timepoint [4]

Baseline and 6 months

Secondary outcome [5]

Short Physical Performance Battery

Timepoint [5]

Baseline and 6 months

Secondary outcome [6]

Skin microvessel function measured by Laser Doppler Flowmetry

Timepoint [6]

Baseline and 6 months

Secondary outcome [7]

Echocardiogram to measure left heart function

Timepoint [7]

Baseline and 6 months

Secondary outcome [8]

Fasting bloods – for fasting glucose, insulin, lipids, HbA1C and stored at -80 for future assays of, neurotrophins, serum AGEs plasma cytokine and oxidative stress markers

Timepoint [8]

Baseline and 6 months

Secondary outcome [9]

Usual physical activity measured with accelerometers worn over 7 days (measured at baseline, 3months and in the last week of the intervention or control program);

Timepoint [9]

Baseline, 3 months and last week of the intervention

Secondary outcome [10]

Urine sample to measure albuminuria.

Timepoint [10]

Baseline - before and after VO2max test
6 month follow-up before and after VO2max test

Secondary outcome [11]

Aerobic capacity: VO2max using a treadmill(Bruce or Modified Bruce test)

Timepoint [11]

Baseline and 6 months

Secondary outcome [12]

Knee strength with the short form of the Physiological Profile Assessment
Grip strength with a hand dynamometer

Timepoint [12]

Baseline and 6 months

Eligibility

Key inclusion criteria

Inclusion criteria
1) T2DM as diagnosed by fasting blood glucose greater or equal to 7 mmol/L or HbA1C greater than 6.4 % or 2 hr post-prandial glucose greater than 11 mmol/L according to current American Diabetes Association Guidelines.
2) Age 50-75 years
3) Be willing and able to participate in a structured exercise program for 6-months.

Minimum age

50 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion criteria:
1) any severe medical condition that precludes safe participation in exercise;
2) moderate or severe dementia
3)Known central nervous system disorders that may have confounding effects on cognitive function (e.g. tumour, multiple sclerosis, Parkinsons disease)
4)contra-indication to MRI;
5) exercising greater than the equivalent of 30 minutes once a week in the last 3 months.

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Randomised by central automated allocation procedure based on computer-generated random numbers

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Block randomized within two age strata of 50-65 years and 65-75 years with equal allocation between strata and random block sizes within strata

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

An important aim of this pilot study is to obtain preliminary data on which to base sample size estimates for the main study. The distributions of outcome and study factors will be summarised by means and standard deviations for continuous variables, and by frequencies and percentages for categorical variables. The efficacy analyses will be undertaken as planned in the main study but only for the purpose of estimating change and variability of change in the outcome measures. They will be performed on an intention-to-treat basis, and both without and with multiple imputation of missing data. In addition, we will perform per-protocol analyses of those participants who meet the criterion of at least 70% adherence to their exercise prescription. Adverse event data will be summarised and presented by treatment group and time point in summary tables.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

28/03/2014

Actual

26/06/2014

Date of last participant enrolment

Anticipated

Actual

13/05/2015

Date of last data collection

Anticipated

Actual

20/12/2015

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

TAS

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Alzheimers Australia Dementia Research Foundation Grant

Address [1]

1 Frewin Place, Scullin,
ACT, 2614

Country [1]

Australia

Primary sponsor type

Individual

Name

Dr Michele Callisaya

Address

Stroke and Ageing Research Group
Southern Clinical School, Monash University
Level 5 E Block Monash Medical Centre 246 Clayton Road, Clayton Victoria 3168

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Associate Professor Velandai Srikanth

Address [1]

Stroke and Ageing Research Group
Southern Clinical School, Monash University
Level 5 E Block, Monash Medical Centre 246 Clayton Road, Clayton Victoria 3168

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research Ethics Committee (Tasmania) Network

Ethics committee address [1]

University of Tasmania
Private Bag 01
Hobart Tasmania 7005

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

21/01/2014

Ethics approval number [1]

H13664

Ethics committee name [2]

Deakin University Human Research Ethics Committee (DUHREC)

Ethics committee address [2]

70 Elgar Road Burwood Victoria
Postal: 221 Burwood Highway
Burwood Victoria 3125 Australia

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

04/02/2014

Ethics approval number [2]

2014-012

Ethics committee name [3]

Monash University Human Research Ethics Committee

Ethics committee address [3]

Building 3E Clayton Campus
Monash University Clayton Victoria

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

Approval date [3]

03/02/2014

Ethics approval number [3]

CF14/281-201400009

Ethics committee name [4]

Human Research Ethics Office of The University of Western Australia

Ethics committee address [4]

University of Western Australia

Ethics committee country [4]

Australia

Date submitted for ethics approval [4]

Approval date [4]

24/01/2014

Ethics approval number [4]

RA/4/1/6611

Summary

Brief summary

Type 2 Diabetes (T2DM) is a significant risk factor for dementia in older people, and vascular disease may underlie this relationship. Greater physical activity is associated with better brain function and is also recommended for people with T2DM to reduce cardiovascular risk. However, it is currently unknown as to whether an exercise intervention can preserve or improve brain health in people with T2DM.

The aim of this project is to examine the efficacy of a six month structured exercise program in preserving brain health in late middle aged people with T2DM, and evaluate whether this occurs by improving vascular health. This will be done by using MRI scans to measure brain perfusion and structure, sophisticated measures of large and small artery health, and cognitive function before and after the intervention.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Michele Callisaya

Address

Stroke and Ageing Research Group
Southern Clinical School
Level 5 E Block,
Monash Medical Centre Monash Univeristy
246 Clayton Road, Clayton Victoria 3168

Country

Australia

Phone

+61 3 62264785

Fax

[email protected]

Contact person for public queries

Name

Dr Michele Callisaya

Address

Stroke and Ageing Research Group
Southern Clinical School
Level 5 E Block,
Monash Medical Centre Monash Univeristy
246 Clayton Road, Clayton Victoria 3168

Country

Australia

Phone

+61 3 62264785

Fax

[email protected]

Contact person for scientific queries

Name

Dr Michele Callisaya

Address

Stroke and Ageing Research Group
Southern Clinical School
Level 5 E Block,
Monash Medical Centre Monash Univeristy
246 Clayton Road, Clayton Victoria 3168

Country

Australia

Phone

+61 3 62264785

Fax

[email protected]

Data sharing statement

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

Yes

What data in particular will be shared?

All de-identified individual participant data collected during the trial

When will data be available (start and end dates)?

now for 5 years

Available to whom?

Researchers who provide a methodologically sound proposal, case-by-case basis at the discretion of Primary Sponsor

Available for what types of analyses?

Those that meet the aims of the approved proposal

How or where can data be obtained?

Request to CI and via signing a data sharing agreement

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		J Alzheimers Dis. 2017;59(2):503-513. doi: 10.3233... [More Details]
Plain language summary	No		Type 2 Diabetes (T2D) is associated with increased... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Feasibility of a multi-modal exercise program on cognition in older adults with Type 2 diabetes - a pilot randomised controlled trial.	2017	https://dx.doi.org/10.1186/s12877-017-0635-9

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

Trial Review

Documents added manually

Documents added automatically