Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000181505
Ethics application status
Approved
Date submitted
23/01/2015
Date registered
24/02/2015
Date last updated
5/02/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of Dietary Protein Supplementation Combined with Exercise Training on Diabetic Rehabilitation in Overweight/Obese Adults with Type-2 Diabetes
Scientific title
The effect of a novel wool-derived dietary protein supplementation on chronic exercise-training induced changes in insulin sensitivity in overweight/obese males with type-2 diabetes
Secondary ID [1] 286045 0
none
Universal Trial Number (UTN)
U1111-1166-4921
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-insulin dependent type-2 diabetes 294023 0
Condition category
Condition code
Metabolic and Endocrine 294324 294324 0 0
Diabetes
Physical Medicine / Rehabilitation 294459 294459 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Longitudinal clinical trial, utilizing a randomized double-blind cross-over design. The study duration will be 22 weeks, consisting of:

Weeks 1-4: normalization (exercise + placebo)
Week 4-5: baseline testing (no exercise / no supplementation)
Week 5-13: Block 1: 8 week exercise plus supplement (placebo or wool derived protein) intervention
Week 13-14: 1 week washout period for testing (no exercise / no supplementation)
Week 14-22: Block 2: 8 week exercise plus supplement (placebo or wool derived protein) intervention
Week 22: post-intervention testing

Normalization: Participants will commence the exercise programme during this period, and all participants will consume the placebo supplement before and after each exercise sessions, and again mid-afternoon. On week 4 all primary (glucose infusion rate) and secondary outcome measurements will be taken, and used as the pre-intervention time-point

Randomization: participants will be allocated to begin the study with either WDP or placebo using the Minimisation method of randomisation.

Supplement: The supplement will be delivered as a chocolate-milk like drink and health bar, to be consumed 3 times per day (pre-training, post-training, mid-afternoon). Each serving of the protein supplement will contain 18 g wool derived protein, 10-25 g carbohydrate, 2-4 g fat. To ensure adherence the participants will be required to complete a 3-day dietary recall each time the visit the laboratory for testing. The supplement will only be consumed on the exercise days, and not during non-exercise days.

Exercise: Exercise Physiologists will supervise 5 days/week intermittent high-intensity mixed-mode, group-based exercise program designed to achieve a fixed-rate 1% gain in exercise load/week. Each training session will be approximately 60 minutes in duration, including:

Warm-up:10 min light cardio machine exercise and stretching
Days 1,3, 5: aerobic (stationary cycle) exercise, comprising 10 x 1-min intervals (70-90% of peak power)
Days 2, 4: circuit training (10-30% of the exercise 1 repetition maximum) emphasising the legs
Cool-down: 5-10 minutes of stretching to cool down

Subjects will be required to attend a minimum of 36 sessions over the 8 weeks, and will be provided with the opportunity to complete any missed sessions on weekends.

Compliance: The participants will be asked to wear an accelerometer for 7 days, and complete 3-day diet diaries on at baseline (week 4), block 1 (weeks 9 and 13), block 2 (weeks 18 and 22).
Intervention code [1] 291033 0
Lifestyle
Intervention code [2] 291131 0
Treatment: Other
Comparator / control treatment
The control supplement will have the protein energy content replaced with by refined carbohydrate (maltodextrin, glucose) and fat to ensure equicaloric energy consumption.
Control group
Placebo

Outcomes
Primary outcome [1] 294124 0
Insulin sensitivity will be assessed with a hyperinsulinemic-euglycemic clamp with a primed continuous infusion of insulin at 120 mU/m2/min (Tam et al, 2012) to achieve endogenous steady-state insulin concentrations and ensure complete inhibition of endogenous-glucose production. An intravenous catheter will be placed in an antecubital vein for infusion of insulin and glucose. A second catheter will be placed anterograde in a dorsal vein of the contralateral hand for blood draws throughout the clamp to establish steady state glucose infusion. The hand will be placed in a rotating-air heating box at 55-65?C for arterialization of venous blood, which will be verified by achieving a hand skin temperature of 37-39?C and the bright-red colour of the blood. A 25% glucose solution will be infused at a variable rate to maintain plasma glucose concentrations between 5.0 and 5.5 mmol/L. The steady-state period will continue for at least 60 min. The mean rate of exogenous glucose infusion during the last 30 min of the 60-min steady state period and between 2 and 2.5 h, will be used to define the glucose infusion rate.
Timepoint [1] 294124 0
At baseline (Week4); on completion of Block 1 (Week 13); and on completion of Block 2 (Week 22)
Secondary outcome [1] 312560 0
GLUT4 density and sarcolemmal translocation using differential centrifugation and immunoblot or ELISA and visualised by immunohistochemistry. Skeletal muscle tissue harvested will be from the vastus lateralis for analysis
Timepoint [1] 312560 0
At baseline (Week4); on completion of Block 1 (Week 13); and on completion of Block 2 (Week 22)
Secondary outcome [2] 312561 0
Insulin-stimulated skeletal muscle (vastus lateralis) mircovascular blood flow, assessed using near-infrared spectroscopy during the
hyperinsulinemic euglycaemic clamp
Timepoint [2] 312561 0
At baseline (Week4); on completion of Block 1 (Week 13); and on completion of Block 2 (Week 22)
Secondary outcome [3] 312562 0
Mitochondrial capacity of the vastus lateralis muscle, assessed using near-infrared spectroscopy
Timepoint [3] 312562 0
At baseline (Week 4); Block 1 (Week 5 and 13); and Block 2 (Week 18 and 22)
Secondary outcome [4] 312563 0
contraction-mediated skeletal muscle (vastus lateralis) microvascular blood flow, assessed using near-infrared spectroscopy during leg-kicking exercise
Timepoint [4] 312563 0
At baseline (Week 4); Block 1 (Week 5 and 13); and Block 2 (Week 18 and 22)
Secondary outcome [5] 312564 0
Blood cholesterol, triglycerides, fasting glucose/insulin, Hb1Ac, alkaline phosphatase, total protein
Timepoint [5] 312564 0
At baseline (Week 4); Block 1 (Week 5 and 13); and Block 2 (Week 18 and 22)
Secondary outcome [6] 312565 0
Metabolomics (urine)
Timepoint [6] 312565 0
At baseline (Week 4); Block 1 (Week 5 and 13); and Block 2 (Week 18 and 22)
Secondary outcome [7] 312566 0
Daily physical activity, assessed over 7 day using accelerometry
Timepoint [7] 312566 0
At baseline (Week 4); Block 1 (Week 5 and 13); and Block 2 (Week 18 and 22)
Secondary outcome [8] 312567 0
Functional health and well-being via psychometric assessment using SF36 and DASS
Timepoint [8] 312567 0
At baseline (Week 4); Block 1 (Week 5 and 13); and Block 2 (Week 18 and 22)
Secondary outcome [9] 312568 0
Body composition, using anthropometry and bio-impedance analysis
Timepoint [9] 312568 0
At baseline (Week 4); Block 1 (Week 5 and 13); and Block 2 (Week 18 and 22)
Secondary outcome [10] 312569 0
Sleep behaviour, assessed over 7 day using accelerometry
Timepoint [10] 312569 0
At baseline (Week 4); Block 1 (Week 5 and 13); and Block 2 (Week 18 and 22)
Secondary outcome [11] 312570 0
Skeletal muscle capillary density by light microscopy. Skeletal muscle tissue harvested will be from the vastus lateralis for analysis
Timepoint [11] 312570 0
At baseline (Week4); on completion of Block 1 (Week 13); and on completion of Block 2 (Week 22)
Secondary outcome [12] 312571 0
Mitochondrial metabolic function will be gauged via citrate synthase and cytochrome oxidase IV activity using ELISA. Skeletal muscle tissue harvested will be from the vastus lateralis.
Timepoint [12] 312571 0
At baseline (Week4); on completion of Block 1 (Week 13); and on completion of Block 2 (Week 22)
Secondary outcome [13] 312572 0
Tissue fibrosis plasticity by endomyosium/myofibril area using light
microscopy. Skeletal muscle tissue harvested will be from the vastus lateralis.
Timepoint [13] 312572 0
At baseline (Week4); on completion of Block 1 (Week 13); and on completion of Block 2 (Week 22)
Secondary outcome [14] 312573 0
phosphorylation status of insulin signalling pathway (PI3K, AS160 on multiple phosphorylation sites) using immunoblot and
immunoflurochemistry. Skeletal muscle tissue harvested will be from the vastus lateralis
Timepoint [14] 312573 0
At baseline (Week4); on completion of Block 1 (Week 13); and on completion of Block 2 (Week 22)
Secondary outcome [15] 312574 0
gene and protein expression using RT-PCR, transcriptome, proteome and associated molecular methods. Skeletal muscle tissue harvested will be from the vastus lateralis.
Timepoint [15] 312574 0
At baseline (Week4); on completion of Block 1 (Week 13); and on completion of Block 2 (Week 22)
Secondary outcome [16] 312575 0
anti-oxidant biology (e.g. glutathione, glutathione peroxidase pathways) using biochemical methods. Skeletal muscle tissue harvested will be from the vastus lateralis.
Timepoint [16] 312575 0
At baseline (Week4); on completion of Block 1 (Week 13); and on completion of Block 2 (Week 22)

Eligibility
Key inclusion criteria
BMI 25-40, HbA1c 7-9%, stable weight and not having participated in regular exercise in the past 6 months
Minimum age
35 Years
Maximum age
60 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
use of beta-blockers, moderate to severe retinopathy, nephropathy and neuropathy, history of cerebrovascular or cardiovascular diseases.

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)
Participants will be recruited through medical centres in Wellington, via flyers and mail-outs to patients. Upon making contact and showing interest, potential participants will be invited to meet with the CI alone or in small groups to read the information sheet and ask questions. The patients’ general practitioner will not be involved in the recruitment process, but may be involved in notification or recommendation. The CI will not place undue influence on potential participants. After baseline testing, a researcher not involved in the study will allocate participants to to begin the study with either wool derived protein or placebo using the Minimisation method of randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization sequence will be generated using the following
internet source (http://www.randomizer.org/form.htm). The
randomization sequence ( wool protein, placebo) will be placed in a sequentially numbered envelope based on the derived
sequence generated by the website
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
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size estimate was based upon the primary outcome, glucose infusion rate (GIR) from analysis of the first completed cohort in the first study in this series (HDEC ref: 13/NTB/69). The statistical rationale and calculations are from Hopkins et al (Med Sci Sports Exerc, 2009. 41: 3-13). The minimum meaningful effect size was set at 23%, a statistically significant outcome following 3 months of diabetic medication (Derosa et al., Metabolism, 2009. 58: 1059-66). GIR has not been measured following chronic amino acid supplementation; however, the improvements in HbA1c, fasting and postprandial blood glucose recorded in T2DM participants following 8 weeks of supplementation (Solerte et al., Am J Cardiol, 2008. 101(11A): 69E-77E exceeded improvements documented in another study comparing the effect of 3 months treatment with hypoglycaemic medication in poorly controlled diabetes (Derosa et al., Metabolism, 2009. 58: 1059-66). In aforementioned supplementation study GIR improved by 23%. In our hands, the estimated typical error of 60 min GIR under similar experimental conditions was 33%. Using magnitude-based inference with the smallest important change of 23%, gives 14 in a crossover, which is sufficient power to yield a 75% likely clinical benefit. If the effect is 14%, there will be sufficient power to declare smallest worthwhile adoption ratio likelihood (66:1) of 25% possible benefit <0.5% harm. Therefore, sixteen participants will be recruited, allowing for a 15% dropout. This study will provide good pilot evidence for the effect size.

The between group effect of treatment will be analysed using mixed linear models via the Proc Mixed utility in SAS (SAS, Cary, NC). Fixed effects within the models will be treatment and time. Random effects (covariance matrix) will be subject, treatment; additional random effects may be added following evaluation of other sources of variability. The baseline values will be added as a covariate to adjust for between-subject variability. Parametric data will be log-transformed prior to analysis, which allows for changes to be expressed as percents and manages heteroscedasticity to adjust residuals to normally-distributed data. Clinical inference and inference to mechanisms outcomes will be via the method of magnitude-based inference.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
1/03/2015
Actual
Date of last participant enrolment
Anticipated
1/06/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment outside Australia
Country [1] 6611 0
New Zealand
State/province [1] 6611 0

Funding & Sponsors
Funding source category [1] 290634 0
Government body
Name [1] 290634 0
Ministry of Business Innovation and Employment
Country [1] 290634 0
New Zealand
Primary sponsor type
University
Name
Massey University
Address
63 Wallace St
Mt Cook, Wellington
6021
Country
New Zealand
Secondary sponsor category [1] 289326 0
None
Name [1] 289326 0
Address [1] 289326 0
Country [1] 289326 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292267 0
Health and Disability Ethics Committee
Ethics committee address [1] 292267 0
Ethics committee country [1] 292267 0
Date submitted for ethics approval [1] 292267 0
26/01/2015
Approval date [1] 292267 0
14/05/2015
Ethics approval number [1] 292267 0

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

Contacts
Principal investigator
Name 54358 0
Dr Lee Stoner
Address 54358 0
School of Sport and Exercise, College of Health, Massey University 63 Wallace St Mt Cook, Wellington, 6021
Country 54358 0
New Zealand
Phone 54358 0
+6421817878
Fax 54358 0
Email 54358 0
[email protected]
Contact person for public queries
Name 54359 0
Lee Stoner
Address 54359 0
School of Sport and Exercise, College of Health, Massey University 63 Wallace St Mt Cook, Wellington, 6021
Country 54359 0
New Zealand
Phone 54359 0
+6421817878
Fax 54359 0
Email 54359 0
[email protected]
Contact person for scientific queries
Name 54360 0
Lee Stoner
Address 54360 0
School of Sport and Exercise, College of Health, Massey University 63 Wallace St Mt Cook, Wellington, 6021
Country 54360 0
New Zealand
Phone 54360 0
+6421817878
Fax 54360 0
Email 54360 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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