Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001172493
Ethics application status
Approved
Date submitted
22/08/2016
Date registered
26/08/2016
Date last updated
3/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of exercise timing on blood glucose control in individuals with Type 2 diabetes mellitus
Scientific title
Exercise and glycaemic control: A randomised controlled trial examining the role of exercise timing in individuals with Type 2 diabetes mellitus
Secondary ID [1] 289991 0
Nil
Universal Trial Number (UTN)
U1111-1186-7232
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 299998 0
Condition category
Condition code
Metabolic and Endocrine 299892 299892 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study Design:
Potential participants will initially be screened by the study coordinator. Participants will then be invited to attend the Exercise Physiology Clinic at Murdoch University for the collection of preliminary measurements and baseline data following attainment of written informed consent. Thereafter, participants from both the T2DM group and Control Group (Healthy but overweight individuals with no T2DM) will be randomly allocated into one of the two intervention training groups (pmEX and amEX) to begin their 12-week exercise training intervention. Mid-intervention assessments will occur during Week 6 to assess: (i) glycemic control and; (ii) aerobic fitness. At least 24 hours after the last training session in week 12, but no more than 96 hours after the last training session, participants will then complete their final assessment of glycaemic control and aerobic fitness.

Procedures:
Participants will continue their medications at the usual dose, frequency and time while participating in this study. Baseline testing will include body anthropometrics (DEXA, height, weight, waist circumference), aerobic fitness assessment (VO2 peak test; modified Bruce treadmill test protocol), diet history, appetite questionnaires, 14-day sleep and physical activity monitoring (Actigraph and diar), 24 h skin temperature (ibutton, data logger), and validated mood chart. Additionally, participants will attend the laboratory (study day) for assessment of PPG and glucose-regulatory hormonal responses as well as assessment of autonomic function. The study day will involve assessment of two distinct postprandial responses (mixed-meal tolerance tests) comprising the first and second meal of the day (second meal phenomenon; the glucose response to the second meal should be less than the first meal). Measures of glycaemic control (HbA1c; 1,5-anhydroglucitol [1,5-AG]) will be collected from the baseline sample into separate EDTA tubes.

Following the baseline assessments, participants will be randomly assigned into their respective intervention groups (amEX and pmEX) for both the T2DM and Healthy Control groups. Randomisation and allocation will be performed on unique study I.D.'s by an independent investigator using randomly permutated blocks (http://www.randomisation.com) with males and females counterbalanced across groups. This list will be then be forwarded back to the study researcher. Participants from both intervention groups will undertake three supervised 55-65 min exercise-training sessions per week (165-190 min supervised per week) for a total of 12 weeks. The exercise training sessions will be performed in groups of 3-5 individuals at Murdoch University Strength and Conditioning gym under the supervision of a trained exercise physiologist. The testing battery for the baseline (pre-) and post-intervention assessments will be identical. The mid-intervention assessment will include 1,5-AG, fasting glucose and VO2 peak test only .

The supervised exercise intervention will consist of a progressive resistance (2-3 sets x 10/12 repetitions; 4 exercises targeting upper- and lower-body performed in a circuit style) and brisk walking (at 65% VO2 peak for 35-45 min). The intensity and volume of both the aerobic and resistance exercises are prescribed in accordance to the American Heart Association scientific statement. The exact exercises and repetitions performed for the resistance exercises will be determined by the supervising exercise physiologist at every training session depending on the participant's fitness levels. Additionally, for the resistance exercises, once the participants are able to complete 12 repetitions for each set of exercises on 2 consecutive exercise sessions (2-by-2 rule), the prescribed intensity of each execise will increase. This process will be overseen by the exercise physiologist during the training sessions. The amEX (0500-1000) will be performed 30-120 min after "breakfast" (food consumption of >200 Cal), while the evening exercise will be performed 30-120 min after the last meal of the day. Participants in the pmEX group will be asked to refrain from consuming food after the evening exercise session. The training workload (volume and intensity) will be monitored closely by the exercise physiologist at every session. All exercise sessions will be recorded in a logbook with attendance taken as well as sessional RPE for each individual training session over the 12-week period. An interviewer-administered 24 h recall will be captured on five separate occasions beyond the diet history assessment to assess diet-related changes (which may be added to the model as a covariate).

Blood analysis:
A total of 15 blood samples (3ml) will be collected during the study-days. A portion of whole blood (200 micro-litres) will be analysed immediately using a clinical benchtop analyser (GEM3500) for metabolites (glucose, lactate, haematocrit). The remaining blood will be transferred into EDTA-coated tubes pre-treated with 30 micro-litres of dipeptidyl peptidase IV inhibitor and aprotinin (Millipore) for later determination of plasma hormone concentrations of insulin, C-peptide, glucagon, GLP-1, and gastric inhibitory polypeptide (GIP) using a MILLIPLEX magnetic bead–based quantitative multiplex immunoassay with the MAGPIX instrumentation (Millipore). Our group has previously published using these techniques and all facilities are available. Baseline samples from each study day will also be assessed for HbA1c (Clinipath Laboratories) and 1,5-AG (Glycomark).
Intervention code [1] 295691 0
Treatment: Other
Comparator / control treatment
Healthy individuals without type 2 diabetes mellitus but are overweight (BMI of more than or equal to 27) will be recruited into the control group in the study. Participants from the control group will undergo the same procedures as the T2DM group (i.e. baseline assessments, random allocation in to amEX or pmEX intervention groups and post-intervention assessments).
Control group
Active

Outcomes
Primary outcome [1] 299369 0
To determine the impact of exercise-timing (morning versus evening) on glycaemic control in individuals enrolled into a 12-week evidence-based multi-modal exercise training program. The measure of glycaemic control will be done through the analysis of HbA1c (glycosylated haemoglobin) levels (%). All blood samples will be sent to an external provider (Clinipath Laboratories) to be assessed.
Timepoint [1] 299369 0
Prior to the start of the 12-week training intervention during baseline assessment (study day) and at least 24 hours after the last training session in week 12, but no more than 96 hours after the last training session (post-intervention study day)
Secondary outcome [1] 326962 0
To determine the impact of exercise-timing (morning versus evening) on diurnal glycaemia in individuals enrolled into a 12-week evidence-based multi-modal exercise training program. Diurnal glycaemia will be assessed during baseline and post-intervention assessment (Study Day) through plasma serum using glucose assay kits.
Timepoint [1] 326962 0
Prior to the start of the 12-week training intervention during baseline assessment (study day) and at least 24 hours after the last training session in week 12, but no more than 96 hours after the last training session (post-intervention study day)

Eligibility
Key inclusion criteria
T2DM Group:
Non-smoking, sedentary (defined as the accrual of less than 150 min of exercise per week) individuals who are overweight (body mass index more than or equal to 27 kg/m2) and have an existing diagnosis of T2DM.

Healthy Control Group:
Non-smoking, sedentary (defined as the accrual of less than 150 min of exercise per week) individuals who are overweight (body mass index more than or equal to 27 kg/m2)
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will not be eligible if: (i) they are unable to complete exercise or have a condition which is known to be aggravated by exercise (assessed using the Exercise and Sports Science Australia pre-exercise screening tool); (ii) they are on insulin; (iii) have had surgery for weight loss; (iv) they had prior history of heart, lung, kidney, endocrine or liver disease; (v) experienced recent weight loss (4 kg or more) in previous month.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Following the baseline assessments, participants will be randomly assigned into their respective intervention groups (amEX and pmEX). Randomisation and allocation will be performed on unique study I.D.'s by an independent investigator using randomly permutated blocks (http://www.randomisation.com) with males and females counterbalanced across groups. This list will be then be forwarded back to the study researcher.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permutated block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
NA
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will presented as means +/- SD. Treatment effects will be estimated using linear mixed models (LMM) to assess for any changes over time (pre-, mid-, post-exercise intervention) in the primary outcome variables between the two groups (amEX, pmEX). The hypothesis of interest is the group by time interaction (modeled as fixed effects; random intercept) which will be examined with pairwise comparisons of the estimated marginal means. Statistical significance will be set at less than 0.05.

Based on Bidwell et al. (reference below), a sample size of 13 participants per intervention group (T2DM amEX, T2DM, pmEX, healthy control amEX and healthy control pmEX) will provide 80% power to detect a significant difference in HbA1c levels when the alpha -error probability is set at 0.05. We therefore aim to recruit 60 participants (15 per group to allow 20% attrition).

Reference: Bidwell AJ, Fairchild TJ, Redmond J, Wang L, Keslacy S, Kanaley JA. Physical activity offsets the negative effects of a high fructose diet. Medicine and science in sports and exercise 2014.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/10/2016
Actual
25/10/2016
Date of last participant enrolment
Anticipated
1/08/2017
Actual
Date of last data collection
Anticipated
31/10/2017
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 294360 0
University
Name [1] 294360 0
Murdoch University
Country [1] 294360 0
Australia
Primary sponsor type
University
Name
Murdoch University
Address
90 South Street, Murdoch, Perth Western Australia 6150
Country
Australia
Secondary sponsor category [1] 293201 0
None
Name [1] 293201 0
Address [1] 293201 0
Country [1] 293201 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295778 0
Murdoch University Human Research Ethics Committee
Ethics committee address [1] 295778 0
Ethics committee country [1] 295778 0
Australia
Date submitted for ethics approval [1] 295778 0
14/08/2015
Approval date [1] 295778 0
12/10/2015
Ethics approval number [1] 295778 0
2015/170

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1042 1042 0 0
/AnzctrAttachments/371347-Ethics Approval.pdf (Ethics approval)
Attachments [2] 1044 1044 0 0
/AnzctrAttachments/371347-INFORMED CONSENT.docx (Participant information/consent)
Attachments [3] 1047 1047 0 0
/AnzctrAttachments/371347-STUDY DAY.docx (Protocol)
Attachments [4] 1048 1048 0 0
/AnzctrAttachments/371347-12-WEEK EXERCISE TRAINING INTERVENTION.docx (Protocol)
Attachments [5] 1049 1049 0 0
/AnzctrAttachments/371347-COMBINED EXERCISE TRAINING PROGRAM.docx (Protocol)
Attachments [6] 1067 1067 0 0
/AnzctrAttachments/371347(v25-08-2016-14-15-08)-INFORMATION LETTER.docx
Attachments [7] 1068 1068 0 0
/AnzctrAttachments/371347(v25-08-2016-14-17-53)-EXPERIMENTAL OVERVIEW (PARTICIPANT COPY).docx
Attachments [8] 1069 1069 0 0
/AnzctrAttachments/371347-TRAINING STUDY OVERVIEW (PARTICIPANT COPY).docx

Contacts
Principal investigator
Name 68446 0
Mr Shaun Teo
Address 68446 0
School of Psychology and Exercise Science
Murdoch University
90 South Street, Murdoch WA 6150
Country 68446 0
Australia
Phone 68446 0
+61423716780
Fax 68446 0
Email 68446 0
[email protected]
Contact person for public queries
Name 68447 0
Shaun Teo
Address 68447 0
School of Psychology and Exercise Science
Murdoch University
90 South Street, Murdoch WA 6150
Country 68447 0
Australia
Phone 68447 0
+61423716780
Fax 68447 0
Email 68447 0
[email protected]
Contact person for scientific queries
Name 68448 0
Shaun Teo
Address 68448 0
School of Psychology and Exercise Science
Murdoch University
90 South Street, Murdoch WA 6150
Country 68448 0
Australia
Phone 68448 0
+61423716780
Fax 68448 0
Email 68448 0
[email protected]

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseThe Effect of Exercise Timing on Glycemic Control: A Randomized Clinical Trial.2020https://dx.doi.org/10.1249/MSS.0000000000002139
N.B. These documents automatically identified may not have been verified by the study sponsor.