We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

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
ACTRN12618001916235
Ethics application status
Approved
Date submitted
24/10/2018
Date registered
26/11/2018
Date last updated
13/12/2019
Date data sharing statement initially provided
26/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effectiveness of a home based strengthening exercise programme combined with oral nutrition in improving muscle mass, strength and function in people aged 65 years and over
Scientific title
Sarcopenia Trial: Resistance training and Oral Nutrition in the aGing (STRONG)- effect on fat free and muscle mass, strength and function in people aged 65 years and over
Secondary ID [1] 296241 0
Nil known
Universal Trial Number (UTN)
U1111-1221-5923
Trial acronym
STRONG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sarcopenia 309883 0
Low bone mineral content 310124 0
Low muscle mass 310125 0
Low muscle strength 310126 0
Inflammation 310128 0
Condition category
Condition code
Diet and Nutrition 308673 308673 0 0
Other diet and nutrition disorders
Musculoskeletal 308674 308674 0 0
Other muscular and skeletal disorders
Musculoskeletal 308675 308675 0 0
Osteoporosis
Inflammatory and Immune System 308873 308873 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will complete a resistance training home exercise programme 4 days per week for 16 weeks (see below) combined with a high dose protein drink:
250ml skim milk (can be lactose free or full cream milk, though must be cow’s milk) mixed with one whole sachet (37.5g) of the study nutritional supplement powder (Juice Plus+® Complete, French Vanilla Blend) , twice daily (after breakfast and after evening meal).

The study drink (skim milk ± study supplement) is to be consumed in addition to the normal background diet. No other changes will be made to the participant’s diet, they will be advised to continue usual intake at mealtimes and snacks.

Resistance Training Programme: Participants will be prescribed a home-based upper and lower limb resistance training programme by a physiotherapist during their initial study visits. The exercise programme will be completed at home independently by the participant between study visits. The participant will return on a monthly basis for review of the programme with the physiotherapist, which will take approximately 1 hour to complete. The exercises will be completed 4 days per week and will take approximately 30-40 minutes to complete each time. Participants will be asked to complete RT exercises in the afternoon, an hour before their evening meal if possible. Specific exercises will include shoulder press, one arm dumbbell row, wall or floor level push ups, calf raisers, sit to stands or squats or lunges. Any musculoskeletal limitations to exercise will be assessed and considered in the prescription of the exercise programme. Load will be prescribed according to the participant’s 10-15 repetition maximum, equivalent to the highest weight the participant is able to lift through the full range of motion of the specified exercise 10-15 times, providing there is no pain reported, which will be re-assessed on a monthly basis during the face to face physiotherapist visits. Resistance will be in the form of hand weights. Progression of load will be advised based on the re-assessed 10-15 repetition maximum weight achieved. The load will only be upgraded under supervision monthly. Progression of the exercise may also involve increasing the effect of gravity for example wall push ups may be progressed towards floor level push ups. The participants will complete 3 sets of 10-15 repetitions. Participants will be advised to complete a diary of the home exercise programme to document what days the programme is completed.

Juice Plus+® Complete, French Vanilla Blend, is classified as a Formulated Supplementary Food and is listed on the front of the label as this. The IP contains a fine, granular powder mainly consisting of protein, fibre and other carbohydrates.

Adherence
Adherence to the study intervention will be monitored and assessed at each visit through sachet countback and review of study diaries. Participants will be asked to fill out the diary each day by recording consumption of the study drink (skim milk ± study supplement) and completion of the home exercises four times per week. Telephone calls and monitoring of muscles mass by BIA during the intervention will be used to help improve adherence to the intervention.
Intervention code [1] 312568 0
Treatment: Other
Comparator / control treatment
The control group will receive the same 16 week exercise programme and instruction as the active group. In addition to the exercise programme, the control group will consume a low dose protein drink consisting of consumption of 250ml skim milk (can be lactose free or full cream milk, though must be cow’s milk) , twice daily (after breakfast and after evening meal).

Adherence
Adherence to the study intervention will be monitored and assessed at each visit through sachet countback and review of study diaries. Participants will be asked to fill out the diary each day by recording consumption of the study drink (skim milk ± study supplement) and completion of the home exercises four times per week. Telephone calls and monitoring of muscles mass by BIA during the intervention will be used to help improve adherence to the intervention.


Control group
Active

Outcomes
Primary outcome [1] 307639 0
Fat Free mass (FFM) (by DEXA)
Timepoint [1] 307639 0
Baseline, mid study (week 8), completion of study (week 16- primary timepoint)
Secondary outcome [1] 352478 0
Body composition (by DEXA).
Timepoint [1] 352478 0
Baseline, mid study (week 8), and completion of study (week 16)
Secondary outcome [2] 352479 0
Bone mineral density (by DEXA)
Timepoint [2] 352479 0
Baseline and completion of study (week 16)
Secondary outcome [3] 352481 0
Muscle protein synthesis markers (plasma IGF-1)
Timepoint [3] 352481 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)
Secondary outcome [4] 352483 0
Systemic protein markers-serum albumin
Timepoint [4] 352483 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)
Secondary outcome [5] 352485 0
Systemic inflammation (plasma TNFa)
Timepoint [5] 352485 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)
Secondary outcome [6] 352486 0
Systemic gene expression of muscle protein synthesis by microarray screening
Timepoint [6] 352486 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)
Secondary outcome [7] 353225 0
Grip strength will be measured by Jamar handgrip dynamometer
Timepoint [7] 353225 0
Baseline (week 0), mid study (week 8) and at completion of study (week 16)
Secondary outcome [8] 353226 0
Physical function will be measured by the Short Performance Physical Battery, 30 second sit to stand test, time up and go test and the Berg Balance Scale.
Timepoint [8] 353226 0
Baseline (week 0), mid study (week 8) and at completion of study (week 16)
Secondary outcome [9] 353227 0
Upper limb strength will be assessed by isometric dynamometry
Timepoint [9] 353227 0
Baseline (week 0), mid study (week 8) and at completion of study (week 16)
Secondary outcome [10] 353228 0
Lower limb strength will be assessed by isometric dynamometry
Timepoint [10] 353228 0
Baseline (week 0), mid study (week 8) and at completion of study (week 16)
Secondary outcome [11] 353229 0
Balance will be assessed by Berg Balance Scale
Timepoint [11] 353229 0
Baseline (week 0), mid study (week 8) and at completion of study (week 16)
Secondary outcome [12] 353686 0
Falls risk will be assessed by the Berg Balance Scale
Timepoint [12] 353686 0
Baseline (week 0), mid study (week 8) and at completion of study (week 16)
Secondary outcome [13] 354342 0
Systemic protein markers-pre-albumin
Timepoint [13] 354342 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)
Secondary outcome [14] 354343 0
Systemic protein markers-creatinine
Timepoint [14] 354343 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)
Secondary outcome [15] 354344 0
Systemic inflammation (sTNFR1)
Timepoint [15] 354344 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)
Secondary outcome [16] 354345 0
Systemic inflammation ( sTNFR2)
Timepoint [16] 354345 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)
Secondary outcome [17] 354346 0
Systemic inflammation (,hsCRP )
Timepoint [17] 354346 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)
Secondary outcome [18] 354347 0
Systemic inflammation ( IL-6)
Timepoint [18] 354347 0
Baseline (week 0), mid study (week 8), and completion of study (week 16)

Eligibility
Key inclusion criteria
Males and females; age 65 years or more
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
BMI >40kg/m2
Usual dietary protein intake >1.0 g/kg BW/day
Participation in resistance exercise (>1 wk), moderate-intensity exercise greater than or equal to 150 min/wk and/or vigorous exercise greater than or equal to 60 min/wk over the past 3 months
Unwilling or unable to undertake resistance training exercise programme (eg severe osteoarthritis)
Unwilling or unable to consume the study drink or cow’s milk
Allergies or intolerance to soy (self-reported)
Regular (>3 times per week) protein supplement (eg. Sustagen) use
Medical conditions requiring a specialised dietary plan (eg insulin dependent diabetes)
Current smokers (smoked within past 6 months)
Abnormal blood chemistry panel at screening
Chronic or excessive alcohol consumption (as evidenced by abnormal liver function tests)
Significant weight loss (>5% BW) in the past 6 months
Current use of systemic anti-inflammatory or immunosuppressant medications (eg corticosteroids)
Current use of medication that may affect muscle metabolism (eg corticosteroids or thyroxine)
Unstable cardiac condition
Diagnosis of renal (eGFR<30) or hepatic failure; terminal illness, human immunodeficiency virus (HIV) or cognitive impairment (Mini mental state exam score <24).
Any other medical condition which may interfere with the participant’s ability to participate in the intervention. For example a diagnosis of osteoporosis and a history of recent multiple non-trauma fractures.

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)
Eligible subjects will be assigned a unique study number according to the randomisation schedule, which will be computer-generated with blocks of variable size and stratified by BMI and gender. The randomisation service will be managed by an independent statistician at the University of Newcastle.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible subjects will be assigned a unique study number according to the randomisation schedule, which will be computer-generated with blocks of variable size and stratified by BMI and gender.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Calculation of Sample Size
Based on previous studies, in order to have 80% power to detect a mean difference in FFM of 0.6 (SD=0.9) kg, we will need n=36 subjects to complete the intervention per group. Allowing for 20% dropouts, we need to recruit 44 subjects per group, a total of n=88 participants.

Analysis of data
Baseline data: Demographic, body composition, muscle strength, physical performance, biomarkers, dietary intake and physical activity data will be compared between groups using unpaired Student’s t test (parametric data) or Mann Whitney U test (non-parametric data).

Intervention results: Following the intervention, study outcomes will be analysed using analysis of covariance (ANCOVA) to test for differences between groups after adjusting for baseline values.

Microarray analysis: Data will be exported to GeneSpring GX version 11 using Illumina’s Genome Studio 3.0. Data will be normalised via log transformation and the baseline converted to the median of all samples. Data will be filtered based on whether the gene is detected as present in 1 or more samples. Gene profiles will be analysed for differential expression by paired T test for significance and fold change in GeneSpring GX version 11. Relationships of gene expression profiles will be examined using hierarchical clustering. Potential molecular mechanisms will be investigated by both gene ontology and pathways analysis in GeneSpring GX 10. We will examine differences in gene expression of subjects before and after the intervention.


Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 28851 0
2305 - New Lambton Heights

Funding & Sponsors
Funding source category [1] 300840 0
Commercial sector/Industry
Name [1] 300840 0
NSA (The Juice Plus+® Company), LLC
Address [1] 300840 0
140 Crescent Drive
Collierville, Tennessee 38017 USA
Country [1] 300840 0
United States of America
Primary sponsor type
University
Name
The University of Newcastle
Address
University Drive, Callaghan New South Wales 2308
Country
Australia
Secondary sponsor category [1] 300570 0
None
Name [1] 300570 0
Address [1] 300570 0
Country [1] 300570 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301607 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 301607 0
Locked Bag No 1
HRMC NSW 2310
Ethics committee country [1] 301607 0
Australia
Date submitted for ethics approval [1] 301607 0
24/09/2018
Approval date [1] 301607 0
27/09/2018
Ethics approval number [1] 301607 0
18/08/15/4.04

Summary
Brief summary
Aging is associated with loss of muscle mass and this accelerates after 60 years of age, even in healthy individuals. This is undesirable, as loss of muscle mass is strongly associated with sarcopenia, increased morbidity and mortality and lower quality of life. Sarcopenia is the age related degenerative loss of skeletal muscle mass, quality, and strength. The cause of sarcopenia with aging is multifactorial, with declines in physical activity and poor nutrition, neuromuscular decline, hormonal changes, systemic inflammation and chronic illness, all being implicated. Interventions to enhance and maintain muscle mass are urgently needed.

This study is a 16 week, randomised controlled trial for adults aged 65 years and over, who are at risk of sarcopenia due to a low protein intake and sedentary lifestyle. Participants complete a home based resistance exercise training programme as well as consume either a high or low dose protein based nutritional drink. The aim of this study is to determine the efficacy of the combined nutritional and exercise approach in improving:

• Body composition
• Bone mineral density
• Muscle strength and function
• Muscle protein synthesis markers
• Systemic protein markers
• Systemic inflammation
• Systemic gene expression of inflammatory/ muscle protein synthesis pathways

We hypothesise that In an older population at risk of sarcopenia, greater improvements in fat free mass, bone mineral content, muscle strength and function can be achieved when a resistance exercise programme is combined with a high dose versus low dose protein based nutritional supplement drink.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87538 0
Prof Lisa Wood
Address 87538 0
Priority Research Centre for Healthy Lungs
Level 2, West Wing, Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights
NSW 2305
Country 87538 0
Australia
Phone 87538 0
+61 2 40420147
Fax 87538 0
+61 2 40420046
Email 87538 0
lisa.wood@newcastle.edu.au
Contact person for public queries
Name 87539 0
Miss Isobel Stoodley
Address 87539 0
Priority Research Centre for Healthy Lungs
Level 2, West Wing, Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights
NSW 2305
Country 87539 0
Australia
Phone 87539 0
+61 2 49854563
Fax 87539 0
+61 2 40420046
Email 87539 0
isobel.stoodley@uon.edu.au
Contact person for scientific queries
Name 87540 0
Prof Lisa Wood
Address 87540 0
Priority Research Centre for Healthy Lungs
Level 2, West Wing, Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights
NSW 2305
Country 87540 0
Australia
Phone 87540 0
+61 2 40420147
Fax 87540 0
+61 2 40420046
Email 87540 0
lisa.wood@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
It is not ethics approved for public sharing of IPD
What supporting documents are/will be available?
Informed consent form
How or where can supporting documents be obtained?
Type [1] 164 0
Informed consent form
Citation [1] 164 0
Link [1] 164 0
Email [1] 164 0
Other [1] 164 0
Summary results
No Results