Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617001224314
Ethics application status
Approved
Date submitted
17/08/2017
Date registered
22/08/2017
Date last updated
22/08/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Geelong Exercise and Nutrition Training Study (GENTS): Examining the Effects of Exercise and/or Calcium-Vitamin D on Bone Health in Older Men
Scientific title
Effects of a Multi-component Exercise Program and Calcium-Vitamin D3 Fortified Milk on Bone Mineral Density, Bone Structure and Strength in Older Men: A Factorial Design Randomised Controlled Trial
Secondary ID [1] 283271 0
Nil
Universal Trial Number (UTN)
N/A
Trial acronym
GENTS Osteoporosis Prevention Study
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 304426 0
Sarcopenia 304427 0
Quality of Life 304428 0
Condition category
Condition code
Musculoskeletal 303757 303757 0 0
Osteoporosis
Musculoskeletal 303758 303758 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an 18-month factorial 2x2 design randomised controlled trial (with a 12 month follow-up) in which community dwelling men aged 50+ years will be randomly allocated to one of four groups: 1) exercise + calcium-vitamin D fortified milk; (2) exercise alone; (3) calcium-vitamin D fortified milk alone; or (4) a usual care control group. Men randomised to the exercise program will be asked to train three times per week (60 minutes per session) and complete a program consisting of moderate to high intensity (60 - 85% of maximum strength) progressive resistance training (PRT) and multidirectional moderate to high impact weight-bearing activities (eg. jumping, hopping). For the first 12 months the exercises will be performed in a slow and controlled manner and for the final 6-months the program will focus on high velocity resistance training (rapid concentric muscle contractions). The exercise program will be run within community leisure centres, individually tailored and supervised by qualified trainers. Exercise logs and completed exercise cards will be regularly checked by the trainers and will be used to monitor exercise adherence. For men allocated to the calcium-vitamin D fortified milk, they will be asked to consume 400 mls/d (2 x 200 ml tetra packs) of reduced fat (1%) ultra-high temperature milk each day. Each 200 ml milk tetra pack will contain approximately 500 mg calcium, 400 IU vitamin D3, 418 kJ energy, 6.6g protein, 2.2 g fat, 11 g lactose, 100 mg sodium and 250 mg phosphorus. Adherence to the milk drink will be monitored using a daily food calendar.
Intervention code [1] 298912 0
Lifestyle
Comparator / control treatment
Participants allocated to the control group will receive their usual care (eg. health and medical assessment/review) from their medical practitioner as required. No placebo will be used in this trial.
Control group
Active

Outcomes
Primary outcome [1] 303123 0
Femoral neck bone mineral density measured by dual energy X-ray absorptiometry (DXA)
Timepoint [1] 303123 0
Baseline then 12, 18 and 30 months after randomisation
Secondary outcome [1] 337943 0
Hip bone mineral density measured by dual energy X-ray absorptiometry (DXA)
Timepoint [1] 337943 0
Baseline then 12, 18 and 30 months after randomisation
Secondary outcome [2] 337944 0
Lumbar spine bone mineral density measured by dual energy X-ray absorptiometry (DXA)
Timepoint [2] 337944 0
Baseline then 12, 18 and 30 months after randomisation
Secondary outcome [3] 337945 0
Total body and regional (arms and legs) lean mass and fat mass measured by dual energy X-ray absorptiometry (DXA)
Timepoint [3] 337945 0
Baseline then 12, 18 and 30 months after randomisation
Secondary outcome [4] 337946 0
Lumbar spine volumetric bone density measured by quantitative computed tomography (QCT)
Timepoint [4] 337946 0
Baseline then 18 months post randomisation
Secondary outcome [5] 337947 0
Mid-femur bone density, cortical bone structure and strength measured by quantitative computed tomography (QCT)
Timepoint [5] 337947 0
Baseline and then 18 months post randomisation
Secondary outcome [6] 337948 0
Mid-tibia bone density, cortical bone structure and strength measured by quantitative computed tomography (QCT)
Timepoint [6] 337948 0
Baseline then 18 months post randomisation
Secondary outcome [7] 337950 0
Muscle cross-sectional area of the legs (mid femur and mid tibia) and back muscles measured by quantitative computed tomography (QCT)
Timepoint [7] 337950 0
Baseline then 18 months post randomisation
Secondary outcome [8] 337956 0
Chest muscle strength (1-repetition maximum strength) measured on a bench press machine.
Timepoint [8] 337956 0
Baseline then 3, 6, 9, 12, 15, and 18 post randomisation
Secondary outcome [9] 337961 0
Balance/sway via the postural sway meter
Timepoint [9] 337961 0
Baseline then 12, 18 and 30 months after randomisation
Secondary outcome [10] 337962 0
Blood pressure
Timepoint [10] 337962 0
Baseline then 12, 18 and 30 months after randomisation
Secondary outcome [11] 337963 0
Cholesterol and blood lipids
Timepoint [11] 337963 0
Baseline then 12 and 18 months post randomisation
Secondary outcome [12] 337964 0
Circulating inflammatory markers including IL-6, TNF-alpha and hs-CRP
Timepoint [12] 337964 0
Baseline then 12 and 18 months post randomisation
Secondary outcome [13] 337965 0
Bone turnover markers including P1NP and CTx
Timepoint [13] 337965 0
Baseline then 12 and 18 months post randomisation
Secondary outcome [14] 337966 0
Serum 25OHD and PTH
Timepoint [14] 337966 0
Baseline then 12 and 18 months post randomisation
Secondary outcome [15] 337967 0
Health-related quality of life using the SF36 questionnaire
Timepoint [15] 337967 0
Baseline then 12 and 18 months post randomisation
Secondary outcome [16] 337968 0
Mood assessed using the abbreviated version of the profile of mood states (POMS) questionnaire
Timepoint [16] 337968 0
Baseline then 12 and 18 months post randomisation
Secondary outcome [17] 337969 0
Habitual physical activity using the CHAMPS questionnaire
Timepoint [17] 337969 0
Baseline then 12 and 18 months post randomisation
Secondary outcome [18] 337971 0
Self reported falls in the previous 12 months
Timepoint [18] 337971 0
Baseline then 12, 18 and 30 months post randomisation
Secondary outcome [19] 337973 0
Bone marrow density (adiposity) derived from QCT scans of the mid femur, mid tibia and lumbar spine
Timepoint [19] 337973 0
Baseline and then 18 months post randomisation
Secondary outcome [20] 338017 0
Back muscle strength (1-repetition maximum strength) measured on a lat pull down machine
Timepoint [20] 338017 0
Baseline then 3, 6, 9, 12, 15, and 18 post randomisation
Secondary outcome [21] 338018 0
Leg muscle strength (1-repetition maximum strength) measured on a leg press machine
Timepoint [21] 338018 0
Baseline then 3, 6, 9, 12, 15, and 18 post randomisation
Secondary outcome [22] 338019 0
Grip strength using hand-held dynamometer
Timepoint [22] 338019 0
Baseline then 3, 6, 9, 12, 15, and 18 post randomisation
Secondary outcome [23] 338020 0
Emotional health assessed using the Center for Epidemiologic Studies Depression Scale (CES-D)
Timepoint [23] 338020 0
Baseline then 12 and 18 months post randomisation
Secondary outcome [24] 338021 0
Lower limb muscle function using the 15 sec step test
Timepoint [24] 338021 0
Baseline then 12, 18 and 30 months after randomisation
Secondary outcome [25] 338022 0
Gait speed via the 6 meter walk test.
Timepoint [25] 338022 0
Baseline then 12, 18 and 30 months after randomisation
Secondary outcome [26] 338024 0
Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) A-Trait Scale
Timepoint [26] 338024 0
Baseline then 12 and 18 months post randomisation

Eligibility
Key inclusion criteria
Community dwelling men aged 50+ years with normal to below average hip or femoral neck bone density (T-score between +0.4 to -2.4 SD).
Minimum age
50 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Use of calcium and/or vitamin D supplements within the past 12 moths, participation in resistance training and/or high-impact weight bearing activities for greater 30 minutes three times per week in the preceding 6 months; BMI of >35 kg/m2; history of osteoporotic fracture or any medical condition or medication use known to affect bone metabolism; lactose intolerant; consumed more than four standard alcoholic drinks per day; current smokers, or any chronic condition that might limit their ability to be involved in the intervention.

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)
Randomisation will be performed by a researcher independent of the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation performed using computer generated random numbers (Excel). Randomisation was stratified according to age (<65 vs >=65 yrs) and dietary calcium intake (<800 vs >=800 mg/d)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analyses will be conducted using Stata on an ITT basis. Where possible, we will obtain all endpoint measures from all withdrawals and include all randomised participants in the final analysis. Baseline characteristics between the groups were compared using analysis of variance (ANOVA). Pooled time series regression analysis for longitudinal data will be used to test for an interaction between exercise and calcium-vitamin D3. If no significant interactions are detected, the main effects of exercise (exercise + fortified milk and exercise alone versus fortified milk and control) and calcium-vitamin D3 fortified milk (exercise + fortified milk and fortified milk versus exercise and controls) will be examined.

Sample size calculations: Using an alpha level of 0.05 and common standard deviation of 1.6% for the change in femoral neck BMD based on data by Prince et al. (J Bone Miner Res 1995), it was estimated that a sample size of 58 men per group would be required to detect a difference between any of the groups with an effect size 0.24 at 80% power (assuming a 15% attrition).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
23/09/2003
Date of last participant enrolment
Anticipated
Actual
19/07/2004
Date of last data collection
Anticipated
Actual
2/02/2007
Sample size
Target
232
Accrual to date
Final
180
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 16951 0
3220 - Geelong
Recruitment postcode(s) [2] 16952 0
3227 - Barwon Heads

Funding & Sponsors
Funding source category [1] 297321 0
Government body
Name [1] 297321 0
Australian Research Council (ARC)
Country [1] 297321 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
School of Exercise and Nutrition Sciences
221 Burwood Highway, Burwood, Melbourne, Victoria 3125
Country
Australia
Secondary sponsor category [1] 296293 0
None
Name [1] 296293 0
Address [1] 296293 0
Country [1] 296293 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298424 0
Deakin University / Barwon Health Human Research Ethics Committee
Ethics committee address [1] 298424 0
Human Research Ethics
Deakin Research Integrity
Deakin University
221 Burwood Highway
Burwood
Victoria 3125
Ethics committee country [1] 298424 0
Australia
Date submitted for ethics approval [1] 298424 0
25/02/2003
Approval date [1] 298424 0
27/03/2003
Ethics approval number [1] 298424 0
EC 03/17

Summary
Brief summary
The aim of this randomised controlled trial is to investigate whether milk fortified with calcium and vitamin D3 combined with high intensity resistance training and weight-bearing impact exercise can lead to a greater effect on BMD at loaded sites than the sum of each factor alone in community-dwelling men aged over 50 years. It is hypothesized that the combination of exercise + calcium-vitamin D fortified milk will lead to greater gains in bone density at the hip than either exercise or calcium-vitamin D alone. This is an 18-month factorial design intervention with a 12-month follow up in which men will be randomised to one of four groups: (1) exercise + fortified milk; (2) exercise alone; (3) fortified milk alone; or (4) a usual control group. The primary outcome is femoral neck bone mineral density. Secondary aims (outcomes) are to: 1) evaluate the effects of the intervention on DXA total hip and lumbar spine BMD, QCT bone density, structure and strength at the spine, femur and tibia, body composition (lean and fat mass and muscle size), muscle strength and function, blood pressure and blood lipids, inflammatory and bone turnover markers, health related quality of life and mood, and 2) evaluate the long-term residual effects (12 months post intervention). The results from this trial will provide important information as to whether food-based nutritional supplementation (calcium-vitamin D enriched milk) can enhance the effects of exercise on musculoskeletal health and function in older men with normal to low bone density.
Trial website
Trial related presentations / publications
Peake J, Kukuljan S, Nowson C, Sanders K, Daly RM. Effects of high intensity resistance training and a milk-based nutrient supplement on markers of inflammation in older men: An 18 month randomised controlled trial. Eur J Appl Physiol 2011 Dec;111(12):3079-88.

Kukuljan S, Nowson C, Bass S, Sanders K, Nicholson G, Seibel M, Salmon J, Daly RM. Independent and Combined Effects of Calcium-Vitamin D3 and Exercise on Bone Structure and Strength in Older Men: An 18-Month Factorial Design Randomized Controlled Trial J Clin Endocrinol Metab 2011 Apr;96(4):955-63.

Kukuljan S, Nowson C, Sanders K, Daly RM. Effects of resistance exercise and fortified milk on skeletal muscle mass, muscle size, and functional performance in middle-aged and older men: an 18-mo randomized controlled trial. J Appl Physiol 107: 1864-1873, 2009.
Public notes

Contacts
Principal investigator
Name 43154 0
Prof Robin Daly
Address 43154 0
Deakin University
Centre for Physical Activity and Nutrition Research
School of Exercise and Nutrition Sciences
221 Burwood Highway
Burwood, Melbourne, Victoria, Australia 3125
Country 43154 0
Australia
Phone 43154 0
+61392446040
Fax 43154 0
Email 43154 0
[email protected]
Contact person for public queries
Name 43155 0
Robin Daly
Address 43155 0
Deakin University
Centre for Physical Activity and Nutrition Research
School of Exercise and Nutrition Sciences
221 Burwood Highway
Burwood, Melbourne, Victoria, Australia 3125
Country 43155 0
Australia
Phone 43155 0
+61392446040
Fax 43155 0
Email 43155 0
[email protected]
Contact person for scientific queries
Name 43156 0
Robin Daly
Address 43156 0
Deakin University
Centre for Physical Activity and Nutrition Research
School of Exercise and Nutrition Sciences
221 Burwood Highway
Burwood, Melbourne, Victoria, Australia 3125
Country 43156 0
Australia
Phone 43156 0
+61392446040
Fax 43156 0
Email 43156 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
EmbaseCirculating Levels of Inflammation and the Effect on Exercise-Related Changes in Bone Mass, Structure and Strength in Middle-Aged and Older Men.2019https://dx.doi.org/10.1007/s00223-018-0475-4
EmbaseChanges in spinal bone density, back muscle size, and visceral adipose tissue and their interaction following a multi-component exercise program in older men: secondary analysis of an 18-month randomized controlled trial.2020https://dx.doi.org/10.1007/s00198-020-05484-z
EmbaseEffects of a multi-modal resistance exercise program and calcium-vitamin D3 fortified milk on blood pressure and blood lipids in middle-aged and older men: secondary analysis of an 18-month factorial design randomised controlled trial.2021https://dx.doi.org/10.1007/s00394-020-02325-x
N.B. These documents automatically identified may not have been verified by the study sponsor.