Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000706774
Ethics application status
Approved
Date submitted
25/06/2013
Date registered
28/06/2013
Date last updated
28/06/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Does bone structure and metabolism contribute to improved insulin sensitivity following exercise in overweight and obese men?
Scientific title
Does undercarboxylated osteocalcin contribute to improved insulin sensitivity following exercise in overweight and obese men?
Secondary ID [1] 282729 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 289459 0
Insulin resistance 289460 0
type 2 diabetes 289461 0
Condition category
Condition code
Metabolic and Endocrine 289775 289775 0 0
Diabetes
Diet and Nutrition 289806 289806 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Euglycaemic, hyperinsulinaemic clamp: acute effects of exercise
Participants will attend our laboratory twice for the experimental trials after an overnight fast. The two trials (exercise or rest) will be conducted 2-4 weeks apart. Session 1: In order to determine the basal (rest) insulin sensitivity as well as resting levels of other biochemical markers, insulin clamp will be performed at rest. In this session two muscle biopsies will be taken, one before and one after 2 hours of insulin clamp. Session 2: In order to examine the effects of exercise on markers of bone formation and resorption as well as insulin sensitivity, mitochondria respiration and glucose control participants will perform high intensity interval exercise (as described below). In this session 3 muscle biopsies will be taken: at baseline, at the start of the insulin clamp (1 h post-exercise) and after the insulin clamp. Insulin clamp will commence after 1 h of recovery.
Blood samples: Blood samples will be taken through an intravenous catheter.

Muscle biopsy: Muscle biopsy (2 in session 1 and 3 in session 2) will be taken from the vastus lateralis. After a local anaesthetic (1% Xylocaine) being injected into the skin and fascia above the vastus lateralis, a small incision will be made and a muscle sample (~150 mg) will be excised.


Session 2: acute high intensity interval exercise: The high intensity exercise protocol will consist of 5 x 4 minute intervals at 90-95% peak heart rate (peak HR), separated by 2 minutes of active recovery consisting of gentle cycling at 50% of peak HR. Peak heart rate will be defined as the highest heart rate measured during the incremental test.

Other assessments will be performed once at baseline (within 2-4 weeks prior session 1).
Anthropometric measurements (10 min):
Height will be measured with the participants standing barefoot on a stadiometer (minus/plus 0.5cm). Weight will be measured with participants wearing just light clothes whilst standing on a calibrated scale. Waist circumference will be measured with a steel tape and taken midway between the iliac crest and the lower border of the ribs. Three measurements will be taken and the mean of the two closest measures will be recorded.

Dual-energy x-ray absorptiometry, DXA (15 min).
Dual-energy X-ray absorptiometry (DXA) (GE Lunar Pxodigy, Software version 9.1, Madison, USA) will be used to assess total body fat and lean body mass (LBM). In addition, the DXA and GE Lunar Pxodigy software will be used to assess fat mass in the abdominal region as well as bone mineral density to exclude osteoporosis. The participants will be asked to lie-down on their back on the DXA table in light closing (no metal) or a gown for approximately 10-15 minutes while the machine scans their body.

High-resolution 3D-pQCT (15 min)
3D-pQCT will be assessed in the distal tibia and radius. High-resolution peripheral quantitative computed tomography-(HR-pQCT) (XtremeCT; Scanco Medical AG, Bassersdorf, Switzerland) will be used in this study, which provides the ability to quantitatively assess volumetric bone mineral density (vBMD), as well as geometric and micro-structural features of human cortical and trabecular bone in a compartmental fashion in the distal radius and tibia. The participants will be asked to seat on a chair with their hand or lower leg inserted into the machine. The scan of each site is 3 minutes and in that time the participant will be asked not to move. Both the arm and lower leg will be supported during the scan. The effective dose is approximately 0.004 microSv for each site. The CVs for the HR-pQCT method for bone mineral density parameters are very low (<1%), with moderate CVs for the morphometric measures (4%-6%).

Fasting blood samples.
A blood sample will be collected from the antecubital vein using a venepuncture technique after an overnight fast of at least 10 hours. Blood will be centrifuged and analysed for total cholesterol, triglyceride, high-density lipoprotein (HDL), low density lipoprotein (LDL), glucose, insulin, c-peptide, high sensitive C-reactive protein (CRP), hepatic enzymes and HbA1c. In addition blood will be analysed for markers of bone formation and bone resorption.


Peak aerobic capacity test
Aerobic power (VO2peak) will be assessed during a symptom-limited graded exercise test on a cycle-ergometer.
The test will start after a 5-minute period at rest. The protocol consists of an initial intensity of 20W, then an increase to 10-20W per minute. The test will be terminated when a participant’s rating of perceived exertion will reach “very hard” [Borg scale = 17], or before that if the patient wishes to stop or clinical signs or symptoms of metabolic or cardiorespiratory abnormalities appeared. Expired respiratory gases will be collected through a breath-by-breath (BxB) pneumotach system connected to gas analysers. The BxB data will be integrated for each 15 sec interval, and the mean values for VO2, VCO2 and ventilation (VE) will be used for that interval. The gas analyser was calibrated immediately before each test using gases that had been calibrated at alpha standard. Heart rate will measure at rest and during the incremental test by 12-lead electrocardiography (Mortara, X-Scribe II, Milwaukee, WI, USA).
Intervention code [1] 287392 0
Other interventions
Comparator / control treatment
We will compare the differences in insulin sensitivity, markers of bone turnover and insulin signalling proteins and mitochondria respiration in skeletal muscle between rest (control) and following acute exercise.
Control group
Active

Outcomes
Primary outcome [1] 289859 0
Insulin sensitivity
Will be assessed by the glucose infusion rate (GIR).
Timepoint [1] 289859 0
Post two hours of euglycaemic, hyperinsulinaemic clamp
Primary outcome [2] 289882 0
Undercarboxylated osteocalcine
Will be measured using an automated immunoassay (Elecsys 170; Roche Diagnostics). This assay has a sensitivity of 0.3 ng/ml, with an intra-assay precision of 4.4%. Serum ucOC will be measured by the same immunoassay after adsorption of carboxylated OC on a hydroxyl-apatite column,
Timepoint [2] 289882 0
Post two hours of euglycaemic, hyperinsulinaemic clamp
Primary outcome [3] 289883 0
insulin signalling proteins
Will be measured using Western blots
Timepoint [3] 289883 0
Post two hours of euglycaemic, hyperinsulinaemic clamp
Secondary outcome [1] 303401 0
bone structure
Will be assessed using HR-pQCT
Timepoint [1] 303401 0
Post 2 hours of euglycaemic, hyperinsulinaemic clamp
Secondary outcome [2] 303466 0
Inflammatory markers
Will be assessed using multiplex
Timepoint [2] 303466 0
Post 2 hours of euglycaemic, hyperinsulinaemic clamp

Eligibility
Key inclusion criteria
Age: 40-70 years.
BMI: 25-40 kg/m^2.
patients with type 2 diabetes will be permitted to participate if they are treated with diet alone.
Minimum age
40 Years
Maximum age
70 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Men with bone disease (such as osteoporosis)
Men who are taking any prescribed medication known to affect bone metabolism, insulin secretion or insulin sensitivity.
Musculoskeletal or orthopaedic condition (such as severe osteoarthritis) that prevents normal daily function (such as walking).
Men with symptomatic or uncontrolled metabolic or cardiovascular disease
warfarin therapy or vitamin K supplementation or restriction

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be recruited from the student and staff body at Victoria University through advertisements in University publications and flyers, as well as global emails to staff and students. We will also recruit from the general public via advertise in articles in newspaper. The contact details of the principal investigator will be included. Potential volunteers will contact the principal investigator who will organize an information session.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/08/2012
Actual
3/09/2012
Date of last participant enrolment
Anticipated
3/10/2013
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 287504 0
University
Name [1] 287504 0
Victoria University
Country [1] 287504 0
Australia
Funding source category [2] 287505 0
Charities/Societies/Foundations
Name [2] 287505 0
National Heart Foundation of Australia: Fellowship
Country [2] 287505 0
Australia
Primary sponsor type
University
Name
Victoria University
Address
Victoria University,
PO Box 14428,
Melbourne, VIC 8001
Country
Australia
Secondary sponsor category [1] 286243 0
None
Name [1] 286243 0
Address [1] 286243 0
Country [1] 286243 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289481 0
Victoria University Human Research Ethics Committee
Ethics committee address [1] 289481 0
Ethics committee country [1] 289481 0
Australia
Date submitted for ethics approval [1] 289481 0
Approval date [1] 289481 0
09/07/2012
Ethics approval number [1] 289481 0
HRETH 12/165

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

Contacts
Principal investigator
Name 41018 0
Dr Itamar Levinger
Address 41018 0
College of Sport and Exercise Science
Institute of Sport, Exercise and Active Living (ISEAL)
Victoria University,
PO Box 14428,
Melbourne, VIC 8001
Country 41018 0
Australia
Phone 41018 0
61 3 9919 5343
Fax 41018 0
Email 41018 0
[email protected]
Contact person for public queries
Name 41019 0
Itamar Levinger
Address 41019 0
College of Sport and Exercise Science
Institute of Sport, Exercise and Active Living (ISEAL)
Victoria University,
PO Box 14428,
Melbourne, VIC 8001
Country 41019 0
Australia
Phone 41019 0
61 3 9919 5343
Fax 41019 0
61 3 9919 5343
Email 41019 0
[email protected]
Contact person for scientific queries
Name 41020 0
Itamar Levinger
Address 41020 0
College of Sport and Exercise Science
Institute of Sport, Exercise and Active Living (ISEAL)
Victoria University,
PO Box 14428,
Melbourne, VIC 8001
Country 41020 0
Australia
Phone 41020 0
61 3 9919 5343
Fax 41020 0
Email 41020 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

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