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Trial registered on ANZCTR


Registration number
ACTRN12618000915257
Ethics application status
Approved
Date submitted
21/05/2018
Date registered
30/05/2018
Date last updated
30/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Preventing Osteoporosis in Patients with Spinal Cord Injury (SCI)
Scientific title
A Prospective Study Aimed at Preventing Osteoporosis in Patients Following an Acute Traumatic Spinal Cord Injury (ASCI) Using Early Intervention with a Potent Anti-Resorptive Therapy, Zoledronic Acid.
Secondary ID [1] 294917 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 307877 0
Spinal Cord Injury (SCI) 307878 0
Condition category
Condition code
Musculoskeletal 306927 306927 0 0
Osteoporosis
Neurological 306928 306928 0 0
Other neurological disorders
Injuries and Accidents 307005 307005 0 0
Fractures
Injuries and Accidents 307006 307006 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single dose of intravenous infusion of 4mg zoledronic acid will be administered by the research nurse, as soon as the participant's serum vitamin D levels are confirmed to be replete, following an acute spinal cord injury.(ASCI).
Baseline pathology tests for musculoskeletal assessment will be performed, with follow. up tests at Month 6, Month 12 and yearly for 5 years. DXA measurements for bone density and body composition will be performed within 6 weeks following the ASCI and yearly for 5 years.
Review in the Metabolic Clinic within 6 weeks of injury, at Month 6, Month 12 and yearly for 5 years.
Intervention code [1] 301231 0
Treatment: Drugs
Intervention code [2] 301232 0
Prevention
Comparator / control treatment
The control group are participants seen 1-5 years following a spinal cord injury (SCI) and not currently on any osteoporosis bisphosphonate therapy.
The control group will receive spinal cord injury therapy standard of care and will undergo the same procedures as the Active/Intervention group, but will not be given intravenous zoledronic acid. The procedures (pathology tests, DXA measurements and review in the Metabolic Clinic) will be performed yearly.
The current bone management standard of care in SCI involves a referral for bone density measurements and a consultation with the Metabolic Unit following a non-traumatic fracture.
The study coordinator will also conduct a retrospective review of our large cohort of chronic SCI sufferers attending the spinal rehab unit. A waiver of informed consent has been approved by the NSLHD Human Research Ethics Committee for this retrospective cohort only. Real-world data on rates of fracture, fracture-related morbidity, associations between SCI-related osteoporosis and other causes of morbidity such as contractures, nephrolithiasis and SCI-osteoporosis will be collected. Other information to be collected will include: patient demographics, relevant past and current medical history, concomitant medications, bone mineral density results; and blood level results including electrolytes, liver and renal function tests, hormones, and markers of bone metabolism.
Control group
Active

Outcomes
Primary outcome [1] 305911 0
Long-term incidence of fracture in SCI patients who have received an infusion of zoledronic acid compared to historical controls who have not received this treatment.
Participants on the active arm of the study will be monitored in the Metabolic Unit by the study team at Baseline, Month 6, Month 12 and annually thereafter for 5 years. A 3-monthly telephone call to the participant will also be made by the study coordinator. Medical records will also be accessed for out-of-study visits to the hospital.
Participants on the control arm of the study will be monitored in the Metabolic Unit at Baseline and then annually thereafter to 5 years post-injury. A 3-monthly phone call to the participant will also be made by the study coordinator. Medical records will also be accessed for out-of-study visits to the hospital
The retrospective review of spinal cord injury patients will be using medical records and spinal cord injury-specific databases.
Timepoint [1] 305911 0
A long period of prospective analysis may be required to establish a difference in fracture rates between the two groups (3-5 years after treatment).
For participants in the active and control arms, data will be collected at Baseline and 3-monthly thereafter up to 5 years post-injury.
Secondary outcome [1] 347007 0
Change in bone density at 12 months and five years following an infusion of zoledronic acid using a dual-energy absorptiometry (DXA) scanner.
Timepoint [1] 347007 0
12 months and 5 years post commencement of intervention
Secondary outcome [2] 347217 0
Change in bone markers at 12 months following an infusion of zoledronic acid. The bone markers of interest are serum CTX and P1NP. Other exploratory markers may also be measured.
Timepoint [2] 347217 0
Blood samples will be collected at Baseline, Month 6, Month 12 and annually thereafter until 5 years post-intervention.
Secondary outcome [3] 347218 0
Change in the rate of nephrolithiasis., assessed clinically. Depending on the level of injury, patients will be assessed for flank pain, urinary tract infection, increased urinary frequency and sepsis. These are all part of the routine clinical care of patients with SCI. If necessary, an abdominal ultrasound will be performed.
Timepoint [3] 347218 0
Clinical assessments at site visits at Baseline, Month 6, Month 12, and annually thereafter until 5 years post-intervention and assessment over the phone every 3 months from baseline to 5 years post-intervention.
Secondary outcome [4] 347219 0
Change in the rate of contractures, assessed clinically. Physical examination at study visits will assess contractures.
Timepoint [4] 347219 0
Clinical assessments at site visits at Baseline, Month 6, Month 12, and annually thereafter until 5 years post-intervention and assessment over the phone every 3 months from baseline to 5 years post-intervention.
Secondary outcome [5] 347266 0
Safety of once-only intravenous zoledronic acid in the acute spinal cord injury population, monitoring with clinical and laboratory assessments. Clinically, patients will have physical examinations, will be questioned on adverse events following drug infusion (acute flu-like illness, fever. etc), and electrolytes, renal function tests and bone metabolism markers (CTX and P1NP) will all be measured routinely as per study schedule. .
Timepoint [5] 347266 0
Clinical assessments at site visits at Baseline, Month 6, Month 12, and annually thereafter until 5 years post-intervention and assessment over the phone every 3 months from baseline to 5 years post-intervention.

Eligibility
Key inclusion criteria
1. Adults aged 18 years and older who have sustained an acute traumatic spinal cord injury.
2. Subject has provided an informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects with a non-traumatic spinal cord injury (eg tumours, degenerative diseases of the spinal column, vascular and autoimmune disorders)
2. Subject is currently involved in another investigational device or drug study, or <30 days since ending another investigational device of drug study or receiving an investigational agent.
3. Malignancy within the past 5 years, except for non-melanoma skin cancers, cervical or breast ductal carcinoma in situ.
4. Subjects with a known sensitivity to any of the drugs to be administered (zoledronic acid, vitamin D if required).
5. Subject is known to have any condition or illness (acute, chronic or history) which, in the opinion of the investigator, might interfere with the evaluation of the study treatment or may otherwise compromise the safety of the patient
6. Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give informed consent and/or to comply with all the required study procedures
7. Female subjects who, at the time of injury, are pregnant.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation is not concealed. This is not a randomized trial so sequence generation will not be performed.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
All patients admitted to Royal North Shore Hospital with an acute traumatic spinal cord injury will be assessed for trial eligibility and offered participation in the active (drug-intervention) arm of study.
All patients within 5 years of a traumatic spinal cord injury will be offered participation in the control arm of the study.
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Comparisons will be made of patients entering the prospective study protocol and receiving zoledronic acid with a historical age-matched control group receiving anti-resorptive treatment (zoledronic acid) in chronic SCI or not receiving zoledronic acid will be made.

Sample Size Estimation:
Assuming that early treatment results in a 25% reduction in long-term fracture risk, ~ 100 participants receiving treatment would be required versus a similar control group (alpha 0.05). In 12 months, RNSH services 80 new SCI cases and therefore, over an 18-month period, we expect to recruit ~ 100 participants in the active arm of the study.

Statistical Analysis Plan:
Basic statistics assessing differences in primary and secondary outcome measures in control and treatment groups will be employed (Student t-tests, chi squared analysis). More advanced statistics involving multivariate analyses and adjustment for co-variates will be considered as the study commences, depending on specific differences observed in prospective versus historical control arms.

Recruitment
Recruitment status
Not yet 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 hospital [1] 10915 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 22677 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 299498 0
University
Name [1] 299498 0
University of Sydney Musculoskeletal, Bone & Joint Health Alliance
Address [1] 299498 0
Faculty of Health Sciences
Room 224, Block S, Cumberland
City Rd
The University of Sydney NSW 2006
Country [1] 299498 0
Australia
Funding source category [2] 299499 0
Hospital
Name [2] 299499 0
Department of Endocrinology, Royal North Shore Hospital
Address [2] 299499 0
Royal North Shore Hospital
Reserve Rd
St Leonards NSW 2065
Country [2] 299499 0
Australia
Primary sponsor type
Hospital
Name
Northern Sydney Local Health District - Royal North Shore Hospital
Address
Reserve Rd.
St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 298828 0
None
Name [1] 298828 0
Address [1] 298828 0
Country [1] 298828 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300401 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 300401 0
Research Office
Kolling Building, Level 13
Royal North Shore Hospital
Reserve Rd.
St Leonards NSW 2065
Ethics committee country [1] 300401 0
Australia
Date submitted for ethics approval [1] 300401 0
11/12/2017
Approval date [1] 300401 0
08/05/2018
Ethics approval number [1] 300401 0
HREC/17//HAWKE/476

Summary
Brief summary
Osteoporosis is a major cause of morbidity in patients with spinal cord injury (SCI) and is under-recognised in this population. Osteoporosis is universal in SCI sufferers and typically results in pelvic and lower limb fractures which heighten the risk of limb contracture, pressure sores, local bone complications including infection and non-union and thus, increases complication and death rates in this population.
The primary aim and objective of this prospective study is to try and prevent the occurrence of osteoporosis in acute SCI. This aim involves early assessment of musculoskeletal parameters in SCI patients within 8-12 weeks following an acute traumatic spinal cord injury, and the use of a preventative treatment with an already approved osteoporosis drug to prevent the rapid bone loss which occurs in the acute phase of the spinal cord injury.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83542 0
Dr Christian Girgis
Address 83542 0
Department of Endocrinology
Royal North Shore Hospital
Reserve Rd.
St Leonards NSW 2065
Country 83542 0
Australia
Phone 83542 0
+61 2 9463 1680
Fax 83542 0
+61 2 9463 1046
Email 83542 0
Christian.Girgis@sydney.edu.au
Contact person for public queries
Name 83543 0
Ms Liza Nery
Address 83543 0
Department of Endocrinology
Royal North Shore Hospital
Reserve Rd
St Leonards NSW 2065
Country 83543 0
Australia
Phone 83543 0
+61 2 9463 1864
Fax 83543 0
+61 2 9463 1046
Email 83543 0
Liza.Nery@health.nsw.gov.au
Contact person for scientific queries
Name 83544 0
Dr Christian Girgis
Address 83544 0
Department of Endocrinology
Royal North Shore Hospital
Reserve Rd.
St Leonards NSW 2065
Country 83544 0
Australia
Phone 83544 0
+61 2 9463 1680
Fax 83544 0
+61 2 9463 1046
Email 83544 0
Christian.Girgis@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
No Results