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Trial registered on ANZCTR


Registration number
ACTRN12623000867695
Ethics application status
Approved
Date submitted
13/07/2023
Date registered
14/08/2023
Date last updated
20/09/2024
Date data sharing statement initially provided
14/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Combining bone-building medication with bone-building exercise in postmenopausal women with low bone mass
Scientific title
ROmosozumab Loaded with EXercise - DUal effects on bone mineral density, muscle and physical function in postmenopausal Osteoporosis and Osteopenia
Secondary ID [1] 310063 0
Nil known
Universal Trial Number (UTN)
U1111-1294-7370
Trial acronym
ROLEX-DUO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
osteopenia 330600 0
osteoporosis 330601 0
Condition category
Condition code
Musculoskeletal 327439 327439 0 0
Osteoporosis
Physical Medicine / Rehabilitation 327607 327607 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1: Drug intervention + Exercise intervention
Group 2: Drug intervention + Exercise control

Drug intervention: 210mg subcutaneous romosozumab injections monthly for 8-months, administered by healthcare professional and adherence reviewed based on study records.

Exercise intervention: HiRIT (high intensity resistance and impact training) - 45-minute sessions twice weekly for 8-months supervised by licenced exercise physiologists or physiotherapists at established exercise facilities. There will be a maximum of 8 participants per group. Adherence to the intervention will be monitored using session attendance logbooks. Exercises will include deadlift, squat, overhead press and jumping exercises. Exercise intensity is assessed using the subjective assessment 'reps in reserve'.
Intervention code [1] 326469 0
Treatment: Drugs
Intervention code [2] 326470 0
Treatment: Other
Comparator / control treatment
Group 3: Drug control + Exercise control

Drug control: volume-matched subcutaneous placebo (normal saline) injections monthly for 8-months

Exercise control: low-intensity exercise - 45-minute sessions twice weekly for 8-months unsupervised at home. The exercise will be performed according to specific instructions provided by study personnel. Adherence will be monitored using attendance logbooks. Exercises will include stretching, balance and bodyweight exercises.
Control group
Placebo

Outcomes
Primary outcome [1] 335299 0
Mean percentage change in lumbar spine bone mineral density (using DXA)
Timepoint [1] 335299 0
Baseline
4 months post-baseline
8 months post-baseline (primary endpoint)
Primary outcome [2] 335300 0
Mean change in seconds taken to complete five times sit to stand test (assessment of lower limb strength and exercise capacity)
Timepoint [2] 335300 0
Baseline
4 months post-baseline
8 months post-baseline (primary endpoint)
Secondary outcome [1] 423800 0
Mean percentage change in femoral neck BMD (using DXA)
Timepoint [1] 423800 0
Baseline
4 months post-baseline
8 months post-baseline
Secondary outcome [2] 423801 0
Mean percentage change in total hip BMD (using DXA)
Timepoint [2] 423801 0
Baseline
4 months post-baseline
8 months post-baseline
Secondary outcome [3] 423802 0
Mean percentage change in distal radius BMD (using DXA)
Timepoint [3] 423802 0
Baseline
4 months post-baseline
8 months post-baseline
Secondary outcome [4] 423803 0
Mean percentage change in cortical bone volume of the proximal femur derived from DXA scan using 3D shaper software.
Timepoint [4] 423803 0
Baseline
4 months post-baseline
8 months post-baseline
Secondary outcome [5] 423804 0
Mean percentage change in parameters of geometry of the proximal femur derived from DXA scan using 3D shaper software.
Timepoint [5] 423804 0
Baseline
4 months post-baseline
8 months post-baseline
Secondary outcome [6] 423805 0
Mean percentage change in serum markers of bone turnover (CTx, P1NP, bone-specific ALP)
Timepoint [6] 423805 0
Baseline
1-month post-baseline
2-months post-baseline
3-months post-baseline
4-months post-baseline
6-months post-baseline
8-months post-baseline
Secondary outcome [7] 423806 0
Mean percentage change in serum DKK1 concentrations
Timepoint [7] 423806 0
Baseline
1-month post-baseline
2-months post-baseline
3-months post-baseline
4-months post-baseline
6-months post-baseline
8-months post-baseline
Secondary outcome [8] 423808 0
Mean percentage change in serum myostatin concentrations
Timepoint [8] 423808 0
Baseline
1-month post-baseline
2-months post-baseline
3-months post-baseline
4-months post-baseline
6-months post-baseline
8-months post-baseline
Secondary outcome [9] 423809 0
Mean percentage change in serum bone biomarker concentrations (OPG, RANKL)
Timepoint [9] 423809 0
Baseline
1-month post-baseline
2-months post-baseline
3-months post-baseline
4-months post-baseline
6-months post-baseline
8-months post-baseline
Secondary outcome [10] 423810 0
Mean percentage change in serum markers of inflammation (IL-6, TNF-a, IL1)
Timepoint [10] 423810 0
Baseline
1-month post-baseline
2-months post-baseline
3-months post-baseline
4-months post-baseline
6-months post-baseline
8-months post-baseline
Secondary outcome [11] 423812 0
Mean difference in time taken (seconds) to complete timed up and go test (assessment of mobility)
Timepoint [11] 423812 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [12] 423813 0
Mean difference in gait speed (metres/second) using 6 metre walk test
Timepoint [12] 423813 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [13] 423814 0
Mean difference in distance (centimetres) using functional reach test (assessment of dynamic balance)
Timepoint [13] 423814 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [14] 423815 0
Mean difference in time to complete (seconds) and number of mistakes using the 6-metre tandem walk test (assessed as composite outcome, assessment of dynamic balance)
Timepoint [14] 423815 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [15] 423816 0
Mean difference in distance (centimetres) between tragus to wall using tragus to wall test (assessment of posture)
Timepoint [15] 423816 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [16] 423817 0
Mean difference in markers of whole body composition using DXA (fat mass, fat percentage, lean mass, lean appendicular mass, skeletal muscle index)
Timepoint [16] 423817 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [17] 423818 0
Mean difference in handgrip strength (kilograms) using dynamometer, including both right and left arm
Timepoint [17] 423818 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [18] 423819 0
Mean difference in leg extensor strength (kilograms) using dynamometer
Timepoint [18] 423819 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [19] 423820 0
Mean difference in specific domain scores (vasomotor, physical, psychosocial, sexual) using MENQOL menopause symptom burden survey (assessed as composite outcome)
Timepoint [19] 423820 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [20] 423821 0
Mean difference in specific domain scores using SF-36 health-related quality of life questionnaire (assessed as composite outcome)
Timepoint [20] 423821 0
Baseline
4-months post-baseline
8-months post-baseline
Secondary outcome [21] 423822 0
Mean difference in prevalence of falls (based on participant self report during study visit interview)
Timepoint [21] 423822 0
Baseline 8-months post-baseline
Secondary outcome [22] 423823 0
Mean difference in prevalence of vertebral fragility fractures (based on thoracolumbar spine Xray assessment using DXA)
Timepoint [22] 423823 0
Baseline 8-months post-baseline
Secondary outcome [23] 423824 0
Mean difference in prevalence of non-vertebral fragility fractures (based on Xray results, review of medical records)
Timepoint [23] 423824 0
Baseline 8-months post-baseline
Secondary outcome [24] 423825 0
Mean difference in concentration of circulating extracellular vesicles (exosomes) pre- and post-HiRIT exercise session (blood samples)
Timepoint [24] 423825 0
Pre- and post-HIRIT exercise session at 2-4 months post-baseline Pre- and post-HiRIT exercise session at 8-months post-baseline
Secondary outcome [25] 439945 0
Mean percentage change in trabecular bone volume of the proximal femur derived from DXA scan using 3D shaper software.
Timepoint [25] 439945 0
Secondary outcome [26] 439946 0
Mean percentage change in trabecular bone volume of the proximal femur derived from DXA scan using 3D shaper software.
Timepoint [26] 439946 0
Baseline 4-months post-baseline 8-months post-baseline

Eligibility
Key inclusion criteria
- Postmenopausal women aged between 50 years old and 80 years old (inclusive)
- At least 2 years since menopause
- Baseline DXA BMD T-score at lumbar spine, total hip or femoral neck between -1.5 and -3.5 in women aged younger than 70 years old
- Baseline DXA BMD T-score at lumbar spine, total hip or femoral neck between -1.5 and -2.5 in women aged 70 years and older
Minimum age
50 Years
Maximum age
80 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Use of recent osteoporosis pharmacotherapy
- Any baseline DXA BMD T-score at lumbar spine, total hip or femoral neck less than -3.5 SD in women aged younger than 70 years old
- Any baseline DXA BMD T-score at lumbar spine, total hip or femoral neck less than -2.5 SD in women aged 70 years and older
- Prior fragility fracture after the age of 50 years
- Regular use of glucocorticoids at equivalent dose of 5mg prednisone per day or more
- Active untreated secondary osteoporosis
- Untreated vitamin D deficiency or hypocalcaemia
- eGFR <30
- Any prior history of coronary artery/cerebrovascular event
- Active malignancy other than non-melanoma skin cancer or ductal carcinoma in-situ
- Already participating in resistance/high impact exercise at least once per week
- Unable to ambulate independently without aids
- Any contraindication to being able to participate in an exercise program
- Planned leave for at least 4 weeks total (or at least 3 weeks continuous) during the 8-month study period
- Non-fluent in speaking and understanding English

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)
Randomisation performed using central randomisation by online tool and allocation concealed to study investigators
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation with maximal tolerated imbalance method using central randomisation by online tool
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
The total required sample size is 102 subjects (34 per group) to meet at least 80% power for differences in co-primary outcomes. Sample size calculations were performed using R software with senior biostatistician assistance.
For the lumbar spine BMD outcome, effect size was 2%, standard deviation 2.4% derived from similar studies in similar populations, alpha = 0.025, power 80% and drop-out rate 15%, resulting in 34 subjects per group needed.
For the five times sit to stand outcome, effect size was 1.5 seconds, standard deviation 1.5 seconds from similar studies in similar populations, alpha = 0.025, and drop-out rate 15%. A sample size of 34 subjects per group provides power >90%.

Statistical calculations will be performed using IBM® SPSS® software. Results will be reported as per CONSORT guidelines and analyses conducted on intention-to-treat basis. RMANCOVA adjusting for baseline group differences will be used to compare groups for all outcome measures. Multivariate linear regression will be used for changes in primary outcomes. All tests will be two-tailed. Odds ratios will be expressed with 95% confidence intervals. A p-value of <0.05 will be considered statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
29/01/2024
Actual
4/04/2024
Date of last participant enrolment
Anticipated
31/12/2025
Actual
Date of last data collection
Anticipated
2/09/2026
Actual
Sample size
Target
102
Accrual to date
19
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25083 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 25084 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 40751 0
2065 - St Leonards
Recruitment postcode(s) [2] 40752 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 314229 0
Charities/Societies/Foundations
Name [1] 314229 0
Healthy Bones Australia
Country [1] 314229 0
Australia
Funding source category [2] 314231 0
Charities/Societies/Foundations
Name [2] 314231 0
Avant Mutual
Country [2] 314231 0
Australia
Funding source category [3] 314232 0
Charities/Societies/Foundations
Name [3] 314232 0
NORTH Foundation
Country [3] 314232 0
Australia
Primary sponsor type
Hospital
Name
Royal North Shore Hospital
Address
Reserve Rd, St Leonards, NSW, 2065
Country
Australia
Secondary sponsor category [1] 316219 0
None
Name [1] 316219 0
Address [1] 316219 0
Country [1] 316219 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313351 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 313351 0
Ethics committee country [1] 313351 0
Australia
Date submitted for ethics approval [1] 313351 0
Approval date [1] 313351 0
21/06/2023
Ethics approval number [1] 313351 0
2022/ETH01794

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

Contacts
Principal investigator
Name 127842 0
Dr Shejil Kumar
Address 127842 0
Department of Diabetes, Endocrinology & Metabolism, Royal North Shore Hospital, Reserve Rd, St Leonards, NSW, 2065
Country 127842 0
Australia
Phone 127842 0
+61 493881354
Fax 127842 0
+61294631045
Email 127842 0
shejil.kumar@health.nsw.gov.au
Contact person for public queries
Name 127843 0
Shejil Kumar
Address 127843 0
Department of Diabetes, Endocrinology & Metabolism, Royal North Shore Hospital, Reserve Rd, St Leonards, NSW, 2065
Country 127843 0
Australia
Phone 127843 0
+61 493881354
Fax 127843 0
+61294631045
Email 127843 0
shejil.kumar@health.nsw.gov.au
Contact person for scientific queries
Name 127844 0
Shejil Kumar
Address 127844 0
Department of Diabetes, Endocrinology & Metabolism, Royal North Shore Hospital, Reserve Rd, St Leonards, NSW, 2065
Country 127844 0
Australia
Phone 127844 0
+61 493881354
Fax 127844 0
+61294631045
Email 127844 0
shejil.kumar@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.