ANZCTR - Registration

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

ACTRN12618001146280

Ethics application status

Approved

Date submitted

23/06/2018

Date registered

12/07/2018

Date last updated

12/07/2019

Date data sharing statement initially provided

12/07/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Osteogenic Exercise for Musculoskeletal and Metabolic Health during Weight Loss in Sarcopenic Obese Older Adults: A Pilot Study (OSMOSIS-P)

Scientific title

Osteogenic Exercise for Musculoskeletal and Metabolic Health during Weight Loss in Sarcopenic Obese Older Adults: A Pilot Study (OSMOSIS-P)

Secondary ID [1]

None

Universal Trial Number (UTN)

N/A

Trial acronym

OSMOSIS-P

Linked study record

N/A

Health condition

Health condition(s) or problem(s) studied:

Sarcopenic Obesity

Musculoskeletal Health

Metabolic Health

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Musculoskeletal

Other muscular and skeletal disorders

Diet and Nutrition

Obesity

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

During the 12week intervention period, all participants will follow the dietary intervention prescribed and supervised by a licensed dietician with 11 years experience in the field, Equal numbers will be randomised to either gym-based High Intensity Resistance and Impact Training (HiRIT) or home-based aerobic exercise(control) as described below.

Dietary Intervention
To determine the amount of energy in the diet that will be prescribed to each participant, habitual dietary nutrient intake will be assessed using a pre-tested 3-day food record form (two non-consecutive weekdays and one weekend) before the commencement of the study intervention. To complete the food record, study participants will list all the foods and beverages that they have consumed for the whole day, including quantities. From these data, each participant’s diet will be modified by deducting 750 - 1000 kcal from their habitual intake, aiming for at least ~1.0 kg reduction in total body fat per week. Three day food records will be administered at baseline and 12 weeks to constantly monitor the dietary intake of the participants and to ensure compliance. Each participant will be oriented by the study dietician on how to quantify their intake using food models and measuring utensils, as well as on how to reduce food portion sizes and replacing energy-dense foods with those of lower energy density. Food records will be validated by the study investigators through one-on-one interview with the study participant at each time point. Dietary nutrient intake of subjects will be processed using FoodWorks 8 Professional for Windows (Xyris Software (Australia), Pty Ltd), which uses the latest Australian Food and Nutrient Database (AUSNUT) 2011-2013 (FSANZ, 2014). AUSNUT is a database which contains 53 nutrient values for 5740 foods and beverages. The study dietician will conduct telephone interviews every week throughout the intervention to monitor and review dietary intakes and set behavioural goals. Participants with poor dietary compliance, as demonstrated by deviations from the diet prescription during the telephone interviews, will be given a 7-day dietary plan to ensure compliance.
Whey protein isolate and vitamin D (cholecalciferol; 1000 IU/day) supplements will also be provided to ensure adequate intakes of this important nutrient for musculoskeletal health is maintained during dietary restriction. The whey protein isolate will be in powdered form that can be mixed with skim milk or water as the participant prefers. The dose will vary for each participant throughout the intervention as it will be modified based on their estimated current protein intake (reported in food records) to ensure they are meeting a protein intake of 1.0g/kg/day. Vitamin D + calcium supplement will be in capsule form that will be taken orally.

Treatment: High Intensity Resistance and Impact Training
Participants allocated to the HiRiT group in the present study will be given a structured 12week, twice weekly, 30minute, supervised, gym based HiRIT program. Each participant will be encouraged to attend each supervised session by an accredited exercise physiologist at the local gymnasium, Healthwise, at Monash Medical Centre, Clayton and will not be required to pay an entry fee to attend; gym fees will be covered by the study budget and have been negotiated at $5 per exercise session during off peak hours (midmorning and midafternoon). Each exercise session will be performed in small groups with a maximum of 8 participants and attendance will be recorded via an exercise sheet. All exercises will be individually tailored and progressive, considering initial fitness, injuries or illness. The prescribed exercise program will use pinloaded smith machine bar or an olympic bar +/weight plates unless contraindicated. Participants will perform up to 2 sets of 5 repetitions of all four exercises at 50% of 1 Repetition Maximum (RM) to serve as a warmup at each session as required. Participants will be then required to perform 5 sets of 5 repetitions, at an intensity of >80% to 85% 1 RM. Each participant will be encouraged to increase the load of the four prescribed exercises each session while maintaining the desired intensity if able. All participants will be individually prescribed four fundamental exercises (deadlift, overhead press, and back squat and modified jumping chin ups) throughout the intervention period. To ensure safe transition to HiRIT exercise, the first two weeks of the intervention will involve body weight only and low load exercise variants, with a focus on learning the movement patterns. All participants will be able to perform the four fundamental exercises of the intervention within 4 weeks. Adherence to intervention will be determined through session attendance checklists and accomplished exercise diaries which will be reviewed during weekly followup calls throughout the intervention.

Control
The control group will complete a moderate intensity, home-based aerobic exercise program. Participants will aim to progress to 150mins/week of walking/jogging at moderate intensity, based on self-perceived exertion reported on the Borg scale, and maintain this for the duration of the home-based intervention. This exercise program is modelled on the Lifestyle Interventions for Elders project and we have used it in previous studies in similar populations. Participants will be asked to complete exercise diaries to assess compliance and these will be reviewed during weekly followup calls throughout the intervention.

Intervention code [1]

Treatment: Other

Comparator / control treatment

The control group will complete a moderate intensity (12-14 on a 20 point Borg RPE scale), home-based aerobic exercise program. Participants will aim to progress to 150mins/week of walking/jogging (in any combination, 30 mins x 5 sessions every week) at moderate intensity, based on self-perceived exertion reported on the Borg scale, and maintain this for the duration of the home-based intervention. This exercise program is modelled on the Lifestyle Interventions for Elders project and we have used it in previous studies in similar populations. Participants will be asked to complete exercise diaries to assess compliance and these will be reviewed during weekly followup calls throughout the intervention. Both treatment and control group will follow the dietary intervention prescribed by the licensed dietician.

Control group

Active

Outcomes

Primary outcome [1]

Change in usual gait speed over a 4m course using stopwatch.

Timepoint [1]

at baseline and after 12 weeks of intervention

Secondary outcome [1]

change in percent body fat using dual-energy X-ray absorptiometry (DXA) scan (Hologic Discovery A, Hologic, USA),

Timepoint [1]

at baseline and after 12 weeks of intervention

Secondary outcome [2]

Serum samples will be analysed for changes in lipid profile (triglycerides (TG), low density lipoprotein, and total cholesterol)

Timepoint [2]

at baseline and after 12 weeks of intervention

Secondary outcome [3]

change in height (using a wall mounted stadiometer (Seca 213, Seca, Germany).

Timepoint [3]

at baseline and after 12 weeks of intervention

Secondary outcome [4]

changes in blood pressure will be measured using a digital blood pressure monitor (Welch Allyn Connex Pro BP 3400, Welch Allyn, USA).

Timepoint [4]

at baseline and after 12 weeks

Secondary outcome [5]

change in health related quality of life using CDC Healthy Days Questionnaire

Timepoint [5]

at baseline and after 12 weeks of intervention

Secondary outcome [6]

changes in physical activity levels which includes data on steps/day using Actigraph wGT3X-BT accelerometer (Actigraph, USA)

Timepoint [6]

at baseline and after 12 weeks of intervention

Secondary outcome [7]

Change in standing balance using stopwatch

Timepoint [7]

at baseline and after 12 weeks of intervention

Secondary outcome [8]

Change in semi-tandem stand using stopwatch

Timepoint [8]

at baseline and after 12 weeks of intervention

Secondary outcome [9]

Change in full tandem stand using stopwatch

Timepoint [9]

at baseline and after 12 weeks of intervention

Secondary outcome [10]

Change in stair climb power test using stopwatch

Timepoint [10]

at baseline and after 12 weeks of intervention

Secondary outcome [11]

change in bone mineral density using dual-energy X-ray absorptiometry (DXA) scan (Hologic Discovery A, Hologic, USA), and quantitative ultrasonography (Hologic Sahara Bone Sonometer, Hologic, USA);

Timepoint [11]

at baseline and after 12 week of intervention

Secondary outcome [12]

change in bone microarchitecture using Tibial Peripheral Quantitative Computed Tomography (pQCT) and High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT)

Timepoint [12]

at baseline and after 12 week of intervention

Secondary outcome [13]

Serum samples will be analysed for changes in glucose level

Timepoint [13]

at baseline and after 12 weeks of intervention

Secondary outcome [14]

Serum samples will be analysed for changes in insulin level

Timepoint [14]

at baseline and after 12 weeks of intervention

Secondary outcome [15]

Serum samples will be analysed for changes in high-sensitivity C-reactive protein (hs-CRP)

Timepoint [15]

at baseline and after 12 weeks of intervention

Secondary outcome [16]

Serum samples will be analysed for changes serum 25-hydroxyvitamin D (25OHD)

Timepoint [16]

at baseline and after 12 weeks of intervention

Secondary outcome [17]

Serum samples will be analysed for changes in bone markers such as serum type 1 collagen type 1 C-telopeptide (CTX) and type 1 procollagen N-terminal peptide (PINP)

Timepoint [17]

at baseline and after 12 weeks of intervention

Secondary outcome [18]

change in weight (using electronic scales, Seca 804, Seca, Germany)

Timepoint [18]

at baseline and after 12 weeks of intervention

Secondary outcome [19]

change in waist circumference (using a measuring tape (Seca 203))

Timepoint [19]

at baseline and after 12 weeks of intervention

Secondary outcome [20]

changes in heart rate will be measured using a digital blood pressure monitor (Welch Allyn Connex Pro BP 3400, Welch Allyn, USA).

Timepoint [20]

at baseline and after 12 weeks of intervention

Secondary outcome [21]

change in falls risk using Modified Falls Efficacy Scale

Timepoint [21]

at baseline and after 12 weeks

Secondary outcome [22]

Change in handgrip strength using Jamar hydraulic hand grip dynamometer (Lafayette Instrument Company, USA),

Timepoint [22]

at baseline and after 12 weeks intervention

Secondary outcome [23]

change in hip circumference (using a measuring tape (Seca 203))

Timepoint [23]

at baseline and after 12 weeks of intervention

Secondary outcome [24]

change in sarcopenia quality of life using Sarcopenia Quality of Life Questionnaire (SarQoL)

Timepoint [24]

at baseline and after 12 weeks of intervention

Secondary outcome [25]

change in lean body mass using dual-energy X-ray absorptiometry (DXA) scan (Hologic Discovery A, Hologic, USA),

Timepoint [25]

at baseline and after 12 weeks of intervention

Secondary outcome [26]

change in health related quality of life using EuroQol-5D-5L

Timepoint [26]

at baseline and after 12 weeks of intervention

Secondary outcome [27]

changes in physical activity levels which includes data on moderate and vigorous activity and sedentary time using Actigraph wGT3X-BT accelerometer (Actigraph, USA)

Timepoint [27]

at baseline and after 12 weeks of intervention

Secondary outcome [28]

Serum samples will be analysed for changes in gamma-glutamyl transferase (GGT), aspartate transaminase (AST), platelet count, albumin and alanine aminotransferase (ALT).

This is a composite secondary outcome.

Timepoint [28]

at baseline and after 12 weeks of intervention

Eligibility

Key inclusion criteria

Prospective participants must be aged 60-89 years; have a body mass index (BMI) of 28 kg/m2; and a body fat percentage of greater than or equal to 30 (men) or of greater than or equal to 40 (women) determined by dual-energy X-ray absorptiometry (DXA); a Short Physical Performance Battery (SPPB) score of of less than or equal to 11 out of 12 indicating presence of a mobility limitation; willing, and has GP approval to complete a 12-week diet and exercise intervention; and also be willing to participate should they be randomised to either intervention arm.

Minimum age

60 Years

Maximum age

89 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Participants are ineligible if they currently reside in a nursing home; are unable to walk 400m in 15 minutes without use of walking aids; are non-English speaking or have difficulty communicating with study personnel due to speech or hearing problems; have moderate or severe cognitive impairment defined as a Mini-Mental State Exam (MMSE) score of of less than or equal to 18 points out of 30; report 4 weeks or more of self-reported participation in a supervised exercise or dietary program targeted at weight loss or strength gains in the past six months; taking any medication or supplements that facilitate weight loss; are planning to be away from home for 4 weeks or more during the intervention; and self-reported diagnosis of: progressive neurological disorders including Parkinson’s Disease and multiple sclerosis; schizophrenia or bipolar disorder; severe knee or hip osteoarthritis (awaiting a joint replacement) that would interfere with ability to complete functional tests; cardiovascular disease (including NYHA Class III or IV congestive heart failure, clinically significant valvular disease, history of cardiac arrest, presence of an implantable cardiac defibrillator, or uncontrolled angina); lung disease requiring regular use of corticosteroids or supplemental oxygen; renal disease requiring dialysis; hyper- or hypothyroidism that would interfere with the weight loss program; and any other disorder of such severity that life expectancy is less than 12 months. Temporary exclusion criteria will include hip or knee replacement, spinal surgery, stroke, myocardial infarction, major heart surgery, deep vein thrombosis, or pulmonary embolus in the past 6 months.

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)

Central randomisation by phone/fax/computer

This study is a single-blind randomised controlled trial in that investigators collecting outcome measures will be blinded to exercise allocation of participants. As this trial involves exercise interventions, it is not possible to blind participants to their intervention arm allocation. Participants will be randomised to gym-based HiRIT or home-based aerobic exercise (control) using computer-generated block randomisation of numbers.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Randomization using computer-generated block randomisation of numbers.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Sample Size
It is not feasible to include falls as a primary outcome for this pilot study given that this would demand larger sample sizes and longer follow-up periods than can be supported by available funding. Therefore, change in usual gait speed over a 4m course from baseline to follow-up will be the primary outcome for the present study. Usual gait speed is recommended as a single assessment for functional outcomes including falls in older adults, and our analyses of the CHAMP cohort, suggest poor gait speed is the primary contributor to increased falls risk in sarcopenic obesity. We will recruit a total sample size of 60 subjects (equal numbers of males and females), with 30 allocated to each arm. Adjusting for a loss to follow-up of 20%, this sample size is large enough to detect a clinically meaningful 0.10m/s (0.12m/s SD) difference in usual gait speed between the HiRIT and control groups.

Statistical Analysis
At the completion of the study, all data will be entered into a secure Microsoft Access database. Data will be exported to an SPSS file and each variable inspected for data errors. In the case of missing or spurious data, original files will be consulted to identify the correct values. When correct values cannot be confirmed, the data point will be classified as missing. Non-normal data will be transformed to meet normality assumptions of parametric methods, or non-parametric methods will be used where appropriate. Independent samples t-tests and Mann-Whitney U tests will be used to compare baseline and change values for physical function, body composition and bone parameters between the treatment and control groups. For all analyses, a P-value of <0.05 or 95% confidence interval not including the null point will be considered statistically significant. All data will be analysed using SPSS Statistics Version 24 (IBM, USA).

Additional Analyses
We may additionally analyse baseline associations between body composition, physical activity and physical function using Pearson and Spearman correlations.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

23/07/2018

Actual

27/02/2019

Date of last participant enrolment

Anticipated

23/08/2020

Actual

Date of last data collection

Anticipated

23/11/2020

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Monash Medical Centre - Clayton campus - Clayton

Recruitment postcode(s) [1]

3168 - Clayton

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Rebecca L. Cooper Medical Research Foundation

Address [1]

Suite 26, Level 1
100 New South Head Road
Edgecliff NSW 2027

Country [1]

Australia

Primary sponsor type

Individual

Name

Dr. David Scott

Address

Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, Australia 3168

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Prof. Peter Ebeling

Address [1]

Department of Medicine,
Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, Australia 3168.

Country [1]

Australia

Secondary sponsor category [2]

Individual

Name [2]

Mavil May Cervo

Address [2]

Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, 3168.

Country [2]

Australia

Secondary sponsor category [3]

Individual

Name [3]

Jakub Mesinovic

Address [3]

Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, 3168.

Country [3]

Australia

Secondary sponsor category [4]

Individual

Name [4]

Paul Jansons

Address [4]

Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, 3168.

Country [4]

Australia

Secondary sponsor category [5]

Individual

Name [5]

Anoohya Gandham

Address [5]

Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, 3168.

Country [5]

Australia

Secondary sponsor category [6]

Individual

Name [6]

Carrie-Anne Ng

Address [6]

Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, 3168.

Country [6]

Australia

Secondary sponsor category [7]

Individual

Name [7]

Dr. Michael Braude

Address [7]

Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, 3168.

Country [7]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Health-Human Research Ethics Committee

Ethics committee address [1]

Monash Health
Level 2, I Block
Monash Medical Centre
246 Clayton Road
Clayton Victoria 3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/05/2018

Approval date [1]

01/08/2018

Ethics approval number [1]

HREC/18/MonH/399

Summary

Brief summary

“Sarcopenia” describes the age-related decline in skeletal muscle mass and function which contributes to increased risk of disability and loss of independence. In the presence of obesity, these effects may be exacerbated, and we have demonstrated that the “sarcopenic obese” population have increased risk for falls and fractures, as well as poor cardiometabolic health. We hypothesise that a 12-week gym-based high-intensity resistance and impact training (HiRIT) program will result in significant improvements in physical function, bone quality, insulin sensitivity and glucose tolerance compared with home-based aerobic exercise program (control) in 60 sarcopenic obese community-dwelling older adults undergoing weight loss through dietary intervention. The findings from OSMOSIS-P will contribute to the development of guidelines for exercise in obese older adults at increased risk for functional decline, falls and fractures.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr David Scott

Address

Department of Medicine, School of Clinical Sciences
Monash University
Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, Australia 3168.

Country

Australia

Phone

+61 3 8572 2397

Fax

[email protected]

Contact person for public queries

Name

Dr David Scott

Address

Department of Medicine, School of Clinical Sciences
Monash University
Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, Australia 3168.

Country

Australia

Phone

+61 3 8572 2397

Fax

[email protected]

Contact person for scientific queries

Name

Dr David Scott

Address

Department of Medicine, School of Clinical Sciences
Monash University
Level 5, Block E,
Monash Medical Centre,
246 Clayton Road, Clayton,
Victoria, Australia 3168.

Country

Australia

Phone

+61 3 8572 2397

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

All of the individual participant data collected during the trial, after de-identification.

When will data be available (start and end dates)?

Beginning 3 months following main results publication, with no end date determined.

Available to whom?

De-identified participant data will be provided on case-by-case basis at the discretion of the Principal Investigator.

Available for what types of analyses?

Any analysis approved by the Principal Investigator after submission of an analysis plan by the applicant.

How or where can data be obtained?

After approval by the Principal Investigator, the data will be transferred via a secure data sharing service.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
2855	Study protocol			[email protected]
2856	Ethical approval			[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically