Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000755538
Ethics application status
Approved
Date submitted
25/06/2015
Date registered
21/07/2015
Date last updated
24/03/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effects of acute exercise on insulin sensitivity, bone metabolism and cardiovascular risk factors in healthy young men treated with a single dose of prednisolone
Scientific title
The effects of acute exercise on insulin sensitivity, bone metabolism and cardiovascular risk factors in healthy young men treated with a single dose of prednisolone
Secondary ID [1] 286970 0
None
Universal Trial Number (UTN)
None
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Insulin sensitivity 295431 0
Markers of bone remodelling 295506 0
Markers of inflammation 295507 0
Mitochondria function 295508 0
Condition category
Condition code
Musculoskeletal 295684 295684 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 295765 295765 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Screening
Anthropometric measurements: Height will be measured with the participants standing barefoot on a stadiometer (+/-0.5cm). Weight will be measured with participants wearing just light clothes whilst standing on a calibrated scale.
Dual-energy x-ray absorptiometry, DXA: (GE Lunar Prodigy, 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 Prodigy 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 clothing (no metal) or a gown for approximately 10-15 minutes while the machine scans their body. All DXA measurements will be conducted by staff at the Bone Density Unit, Austin Health Repatriation Campus. DXA is a fast, simple and safe technique to evaluate body composition. DXA method is well established at Austin Health. DXA scan - radiation exposure (for all body scan) is consider very small equal to 0.001 mSv.

High-resolution 3D-pQCT: 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 sit 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 mSv 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 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 will be calibrated immediately before each test as per the manufacturer’s instructions. Heart rate will be measured at rest and during the incremental test via a polar heart rate watch.

Experimental trials
Participants will attend our laboratory twice for the experimental trials. The two trials (prednisolone or placebo) will be performed 2-3 weeks apart. This ensures that the effect of the single dose of prednisolone is “washed out”. 24 hours prior to the first trial day a single muscle biopsy and 15 ml of blood will be taken. To avoid an additional biopsy, data from this resting biopsy will be used as the “24 hour prior” time point for both the placebo and prednisolone trial. Participants will then be given a capsule containing 20mg of prednisolone or placebo (Avicel- microcrystalline Cellulose NF PH105) in a double-blind randomised cross over design, to take home for ingestion at 7pm that night. Participants will be contacted via phone to remind them to take the capsule at 7pm.
Both the prednisolone and placebo will be purchased from Thompsons Pharmacy and the two capsules will look and taste identical. Avicel is widely used as a placebo in a variety of drug trials.
The following day (the trial day) participants will attend our laboratory in the morning (7-8:00am) after an overnight fast. The participant will be asked to consume a single dose (600mg) of SLOW-K (Potassium Chloride) and be asked to lay down on a bed. A resting blood sample, via intravenous catheter, and a resting muscle biopsy will be taken. The high intensity exercise, on a cycle ergometer supervised by an exercise physiologist, will commence 10-20 minutes after the resting muscle biopsy. The 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 cycling at 50-70% of peak intensity. Peak heart rate will be defined as the highest heart rate measured during the incremental test. After completing the exercise, participants will recover for 3h and then a 2h euglycaemic-hyperinsulinaemic clamp (insulin clamp) will be performed. During the clamp blood samples (1.5 ml) will be taken every 5 minutes to monitor blood glucose levels (YSI 2300 STAT Plus, Trademark, Glucose & Lactate Analyser, Australia). A 10 ml blood sample will be taken every 30 min during the clamp. Blood will be centrifuged and serum will be immediately stored in aliquots at -80 degrees Celsius until assayed. In addition, a total of 7 muscle biopsies will be obtained during the study. Four biopsies will be obtained during the first session (-24, baseline and pre and post insulin clamp) and three during the second session (baseline and pre and post insulin clamp).
Glucocorticoid Ingestion (prednisolone): Glucocorticoid ingestion will involve a single oral dose of 20mg of prednisolone or placebo (Avicel). Both substances will be sourced and compounded from Thompsons Pharmacy and delivered in a double blind fashion; only the research team medical doctor and Thomspons Pharmacy staff will know which capsules is placebo or prednisolone.
Intervention code [1] 292176 0
Treatment: Drugs
Comparator / control treatment
Avicel- microcrystalline Cellulose NF PH105
Control group
Placebo

Outcomes
Primary outcome [1] 295390 0
Changes in bone remodelling markers including: total osteocalcin, uncarboxylated osteocalcin, procollagen type 1 N-terminal propeptide and beta-isomerized C-terminal telopeptides.

Blood samples will be collected from the antecubital vein using a venepuncture technique.
Timepoint [1] 295390 0
Baseline, post exercise, 30 min post exercise and 1, 2 and 3 hours post exercise and every 30 minutes during the 2 hour insulin clamp.
Secondary outcome [1] 315497 0
Changes in insulin sensitivity
Timepoint [1] 315497 0
Post insulin clamp. Will be assessed using the Glucose Infusion Rate (GIR) in the last 30 min of the clamp.
Secondary outcome [2] 315498 0
Changes in skeletal muscle metabolism. Will be assessed using a muscle biopsy technique, with suction. Insulin signalling proteins and mitochondria function will be examined.
Timepoint [2] 315498 0
Baseline, 3 hours post exercise and post 2 hour of insulin clamp.
Secondary outcome [3] 315658 0
Changes in markers of cytokines in blood and skeletal muscle. Including IL6, TNF-alpha, MCP1, IL1-beta, atrogin, STAT3, NF-k beta, FoxO1, MuRF1.
Blood samples will be collected from the antecubital vein using a venepuncture technique
Muscle sample: will be taken using muscle biopsy technique, with suction.
Timepoint [3] 315658 0
Baseline, 3 hours post exercise and post 2 hour of insulin clamp.

Eligibility
Key inclusion criteria
Healthy men aged 18-40 years. BMI 19-27 kg/m2. Fasting blood glucose equal or less than 5.6 mmol/L
Minimum age
18 Years
Maximum age
40 Years
Sex
Males
Can healthy volunteers participate?
Yes
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 metabolic or cardiovascular disease
- Volunteers on warfarin therapy or vitamin K supplementation or restriction will be excluded

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)
Allocation is concealed. To determine the order of the treatments (prednisolone or placebo) sealed opaque envelopes will be used.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation. Allocation concealment. The person responsible for the randomisation, the investigators and the participants are unaware of the intervention (prednisolone or placebo, double blind).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
2/03/2015
Actual
19/03/2015
Date of last participant enrolment
Anticipated
1/04/2016
Actual
13/05/2016
Date of last data collection
Anticipated
Actual
15/05/2016
Sample size
Target
12
Accrual to date
Final
9
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 291529 0
University
Name [1] 291529 0
Victoria University
Country [1] 291529 0
Australia
Primary sponsor type
Individual
Name
Itamar Levinger
Address
Institute of Sport, Exercise and Active Living (ISEAL)
College of Sport and Exercise Science
Victoria University,
PO Box 14428,
Melbourne, VIC 8001
Country
Australia
Secondary sponsor category [1] 290210 0
None
Name [1] 290210 0
Address [1] 290210 0
Country [1] 290210 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293070 0
Victoria University Human Research Ethics Committee
Ethics committee address [1] 293070 0
Ethics committee country [1] 293070 0
Australia
Date submitted for ethics approval [1] 293070 0
Approval date [1] 293070 0
19/06/2014
Ethics approval number [1] 293070 0
HRE14-099

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

Contacts
Principal investigator
Name 58342 0
A/Prof Itamar Levinger
Address 58342 0
Institute of Sport, Exercise and Active Living (ISEAL)
College of Sport and Exercise Science
Victoria University,
PO Box 14428,
Melbourne, VIC 8001
Country 58342 0
Australia
Phone 58342 0
+61 3 9919 5343
Fax 58342 0
Email 58342 0
[email protected]
Contact person for public queries
Name 58343 0
Itamar Levinger
Address 58343 0
Institute of Sport, Exercise and Active Living (ISEAL)
College of Sport and Exercise Science
Victoria University,
PO Box 14428,
Melbourne, VIC 8001
Country 58343 0
Australia
Phone 58343 0
+61 3 9919 5343
Fax 58343 0
Email 58343 0
[email protected]
Contact person for scientific queries
Name 58344 0
Itamar Levinger
Address 58344 0
Institute of Sport, Exercise and Active Living (ISEAL)
College of Sport and Exercise Science
Victoria University,
PO Box 14428,
Melbourne, VIC 8001
Country 58344 0
Australia
Phone 58344 0
+61 3 9919 5343
Fax 58344 0
Email 58344 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
EmbaseDetecting the vitamin D receptor (VDR) protein in mouse and human skeletal muscle: Strain-specific, species-specific and inter-individual variation.2023https://dx.doi.org/10.1016/j.mce.2023.112050
N.B. These documents automatically identified may not have been verified by the study sponsor.