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Trial registered on ANZCTR


Registration number
ACTRN12619000636156
Ethics application status
Approved
Date submitted
18/04/2019
Date registered
30/04/2019
Date last updated
28/01/2020
Date data sharing statement initially provided
30/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of HMB and vitamin D supplementation on osteosarcopenia in older persons
Scientific title
A randomised, double-blind, placebo-controlled trial to determine the effect of vitamin D alone or in combination with HMB on osteosarcopenia in older persons
Secondary ID [1] 298012 0
Nil known
Universal Trial Number (UTN)
Trial acronym
EMPIRE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteosarcopenia 312462 0
Condition category
Condition code
Musculoskeletal 311013 311013 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-centre randomised, double-blind, placebo-controlled study design with approximately 88 osteosarcopenic patients randomised to daily treatments: vitamin D3 (1,000 IU/d) together with Beta-hydroxy-beta-methylbutyrate (HMB) or placebo. The study will consist of a 24-week treatment period followed by a 12-week follow-up period. Assessments will be performed at the time of randomisation and at Weeks 12, 24 and 36.

After screening, eligible patients will be randomised in a 1:1 ratio to receive two daily treatments of three soft gel capsules containing vitamin D3 (166.6 IU soft gel capsule) together with HMB (HMB free acid, 0.5 g/soft gel capsule) or placebo (vitamin D3 (166.6 IU/ soft gel capsule).

Subjects will be assigned to one of the following 2 treatment arm to receive oral doses of the following:
Arm 1 - vitamin D3 (1,000 IU/d) together with HMB (3g HMB Free acid/d)
Arm 2 - vitamin D3 (1,000 IU/d) together with placebo

Adherence will be monitored through unused product treatment return to the Clinical Trials Pharmacy.
Intervention code [1] 314245 0
Treatment: Drugs
Comparator / control treatment
Control group receiving two daily treatments of three soft gel capsules containing vitamin D3 (166.6 IU soft gel capsule) and canola oil.
Control group
Active

Outcomes
Primary outcome [1] 319809 0
Gait velocity measured through Short Physical Performance Battery
Timepoint [1] 319809 0
Baseline, Weeks 12 and 24 after treatment commencement (end-of treatment is Week 24), at at week 36 to measure residual effect
Secondary outcome [1] 369582 0
Physical performance measured by the Short Physical Performance Battery score
Timepoint [1] 369582 0
Baseline, Weeks 12 and 24 after treatment commencement (end-of treatment is Week 24), at at week 36 to measure residual effect
Secondary outcome [2] 369583 0
Total lean body mass measured by Dual-energy X-ray absorptiometry (DXA)
Timepoint [2] 369583 0
Baseline, and 24 weeks after treatment commencement
Secondary outcome [3] 369584 0
Composite surrogate fracture risk outcome using serum levels of bone biomarkers CTx and P1NP
Timepoint [3] 369584 0
Randomisation, Weeks 12 and 24 after treatment commencement (end-of treatment is Week 24), at at week 36 to measure residual effect
Secondary outcome [4] 369585 0
Self-reported falls through a falls diary
Timepoint [4] 369585 0
Randomisation, Weeks 12 and 24 after treatment commencement (end-of treatment is Week 24), at at week 36 to measure residual effect
Secondary outcome [5] 369586 0
Residual effect after cessation of HMB supplementation on bone structure and muscle mass (composite measure through pQCT)
Timepoint [5] 369586 0
Week 36 (12 weeks after end-of-treatment)
Secondary outcome [6] 369775 0
Residual effect after cessation of HMB supplementation and physical performance (measured through Short Physical Performance Battery)
Timepoint [6] 369775 0
Week 36 (12 weeks after end-of-treatment)
Secondary outcome [7] 370805 0
Strength measured using hand grip dynamometer
Timepoint [7] 370805 0
Baseline, Weeks 12 and 24 after treatment commencement (end-of treatment is Week 24), at at week 36 to measure residual effect
Secondary outcome [8] 370806 0
Composite measure of muscle mass and bone microarchitecture measured by peripheral quantitative computed tomography (pQCT)
Timepoint [8] 370806 0
Baseline, Weeks 12 and 24 after treatment commencement (end-of treatment is Week 24), at at week 36 to measure residual effect

Eligibility
Key inclusion criteria
• Men and postmenopausal women aged 65 years or older with self-reported
mobility limitations such as difficulty standing up from a chair, walking for longer than 10 minutes on a flat surface or climbing a flight of stairs;
• Grip strength <27 Kg in men and <16 Kg in women;
• Gait speed over 4 meters of less than or equal to 0.8 m/s but more than or equal to 0.3 m/s at screening and baseline;
• BMD T-score less that or equal to -1 SD in femoral neck
• Subjects must weigh at least 35.0 kg to participate in the study and have a body mass index (BMI) within the range of 15.0 – 32.0 kg/m2
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of a lower limb fracture (e.g., femur, tibia) within the past 6 months with persistent negative impact on lower extremity function or any significant impairment or disease adversely impacting gait (e.g., intermittent claudication in advanced peripheral vascular disease, spinal stenosis, or severe osteoarthritis of the knee or hip);
• Neurological injury/disorder with significant persistent neurological or functional deficit (e.g., stroke with hemiparesis, spinal cord injury, muscular dystrophy, myopathy, myasthenia gravis, Parkinson’s disease, peripheral polyneuropathy);
• Medical conditions associated with muscle loss;
• Chronic kidney disease [estimated glomerular filtration rate (GFR) < 30 mL/min];
• History of confirmed chronic obstructive pulmonary disease with a severity grade > 2 on the Medical Research Council Dyspnea Scale;
• Uncontrolled hypothyroidism or hyperthyroidism. Hypothyroid patients who have changed their dose of hormone replacement therapy in the 6 weeks prior to screening are not eligible for the study;
• Underlying muscle diseases, including history of or currently active myopathy (e.g., dermatomyositis, polymyositis, etc.) or muscular dystrophies;
• Confirmed rheumatoid arthritis, acquired immunodeficiency syndrome (AIDS), or type 1 diabetes mellitus;
• History of or ongoing gastrointestinal diseases known to cause malabsorption of protein or energy, such as inflammatory bowel disease, celiac disease, short bowel syndrome, pancreatic insufficiency;
• Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis) or conditions with hepatotoxic potential (e.g., known gallbladder or bile duct disease, acute or chronic pancreatitis);
• Active cancer (i.e., under current treatment), or cancer requiring treatment in the last 5 years excluding non-melanoma skin cancers or cancers with excellent prognosis (e.g., early stage prostate or breast cancer, or carcinoma in situ of the uterine cervix);
• Uncontrolled type 2 diabetes mellitus (i.e., HbA1C greater than or equal to 8.0% or frequent hypoglycemia);
• Any chronic active infection (e.g., HIV, hepatitis B or C, tuberculosis, etc.).
• Active alcohol/drug abuse, or alcohol/drug treatment < 12 months prior to screening; subjects having successfully completed an alcohol/drug treatment program >12 months prior to screening with sustained abstinence are eligible;
• Use of any therapies known to affect muscle mass, including androgens, androgen supplements [including over-the-counter dehydroepiandrosterone (DHEA)], gonadotropin releasing hormone (GnRH) analogues, anti-androgens, anti-estrogens (e.g., tamoxifen), progestins with known androgenic component (e.g., norethindrone acetate), megestrol acetate, high-dose tibolone (2.5 mg), recombinant human growth hormone, growth hormone receptor antagonists (e.g., pregvisomant), oral selective beta-2 agonists, or dronabinol within 3 months prior to randomisation; and any nutritional supplement other than protein marketed as a muscle anabolic.
• Ongoing corticosteroid use, or history of systemic corticosteroid use for at least 3 months (in the last year) prior to screening at a daily dose greater than or equal to 10 milligram (mg) prednisone equivalent.

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 involves contacting the holder of the allocation schedule (unblinded on-site pharmacist)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Each parameter (grip strength, gait velocity, muscle mass, and bone microarchitecture) will be analysed separately using ANCOVA with adjustment for baseline levels of examined parameters to adjust for any residual imbalance following randomisation. Given the parameters are likely correlated, the adjustment for multiple comparisons will not be performed.

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)
VIC
Recruitment hospital [1] 13641 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 26313 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 302541 0
Commercial sector/Industry
Name [1] 302541 0
TSI Pharmaceuticals
Address [1] 302541 0
286 Fison Avenue East
Eagle Farm
QLD
4009
Country [1] 302541 0
Australia
Funding source category [2] 302542 0
Government body
Name [2] 302542 0
Department of Industry, Innovation and Science - Innovations Connections Project
Address [2] 302542 0
Industry House
10 Binara Street
Canberra
ACT
2601
Country [2] 302542 0
Australia
Primary sponsor type
Hospital
Name
Western Health
Address
Sunshine Hospital
176-190 Furlong Road
St Albans
VIC
3021
Country
Australia
Secondary sponsor category [1] 302451 0
None
Name [1] 302451 0
Address [1] 302451 0
Country [1] 302451 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303186 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 303186 0
Office for Research
Level 2
South West
300 Grattan Street
Parkville
VIC
3052
Ethics committee country [1] 303186 0
Australia
Date submitted for ethics approval [1] 303186 0
31/05/2019
Approval date [1] 303186 0
20/08/2019
Ethics approval number [1] 303186 0

Summary
Brief summary
The purpose of this study is to determine the efficacy of vitamin D3 with or without HMB on the physical function, skeletal muscle mass, strength, bone turnover and bone microarchitecture in community-dwelling men and women aged 65 years with osteosarcopenia.

This is a single-centre randomised, double-blind, placebo-controlled study design with approximately 88 osteosarcopenic patients randomised to daily oral soft gel capsule treatments: vitamin D3 (1,000 IU/d) together with HMB or placebo. The study will consist of a 24-week treatment period followed by a 12-week follow-up period. Assessments will be performed at the time of randomisation and at Weeks 12, 24 and 36.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92786 0
Prof Gustavo Duque
Address 92786 0
Sunshine Hospital
Level 3, WCHRE Building
176-190 Furlong Road
St Albans
VIC
3021
Country 92786 0
Australia
Phone 92786 0
+61 3 8395 8121
Fax 92786 0
Email 92786 0
gustavo.duque@unimelb.edu.au
Contact person for public queries
Name 92787 0
Prof Gustavo Duque
Address 92787 0
Sunshine Hospital
Level 3, WCHRE Building
176-190 Furlong Road
St Albans
VIC
3021
Country 92787 0
Australia
Phone 92787 0
+61 3 8395 8121
Fax 92787 0
Email 92787 0
gustavo.duque@unimelb.edu.au
Contact person for scientific queries
Name 92788 0
Prof Gustavo Duque
Address 92788 0
Sunshine Hospital
Level 3, WCHRE Building
176-190 Furlong Road
St Albans
VIC
3021
Country 92788 0
Australia
Phone 92788 0
+61 3 8395 8121
Fax 92788 0
Email 92788 0
gustavo.duque@unimelb.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
Deidentified collated data only will be published in academic peer-reviewed publications.
What supporting documents are/will be available?
No other documents available
Summary results
No Results