Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000300673
Ethics application status
Approved
Date submitted
12/03/2014
Date registered
20/03/2014
Date last updated
20/03/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Effect of Bisphosphonates on the Immune System in Adults With Osteoporosis
Scientific title
The effect of bisphosphonate therapy on the human immune system
Secondary ID [1] 284245 0
nil
Universal Trial Number (UTN)
U1111-1154-4303
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 291362 0
Immune system 291363 0
Condition category
Condition code
Musculoskeletal 291727 291727 0 0
Osteoporosis
Inflammatory and Immune System 291728 291728 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients who are bisphosphonate naive and have been instructed to start bisphosphonate therapy by their physician will be eligible to be enrolled in this trial. The treatment with either weekly oral bisphosphonate (Alendronate or Risedronate) or single IV bisphosphonate (Zoledronic acid) will be made based on patient preference and best clinical practice, The choice of treatment will be made prior to enrolment in the study and will not be influenced by the study.
The study involves two or three additional blood tests and visits in addition to the blood tests that occur as part of routine care. Routine care involves baseline bloods completed prior to commencing therapy, and then blood tests at 6 and 12 months. Patients receiving intravenous bisphosphonate therapy will have three additional blood tests (i.e. 1 day, 1 week and 1 month following the intravenous therapy). Patients receiving oral bisphosphonates then you will receive two additional blood tests (1 week and 1 month after starting the oral therapy).
The blood samples will then be analysed to test for the presence of bisphosphonate within the myeloid cells of the human immune system.
Intervention code [1] 288954 0
Not applicable
Comparator / control treatment
Each patient will serves as their own control as the primary blood test will be prior to bisphosphonate therapy and therefore be a sample without the effects of treatment.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291663 0
To determine whether bisphosphonates are internalized by circulating myeloid cells and inhibit protein prenylation, thereby altering immune cell function.
The inhibition of protein prenylation will be detected by performing a Western Blot on purified myeloid cells from the blood samples.
Timepoint [1] 291663 0
12 months
Secondary outcome [1] 307252 0
To determine how long the effect on myeloid cells can be detected for (ie time of onset and offset of the effect), after single intravenous or continuous oral administration.
This will be assessed by performing Western Blots on the purified blood samples from baseline to 12 months and then determining the duration of inhibition of protein prenylation.
Timepoint [1] 307252 0
12 months

Eligibility
Key inclusion criteria
Sex: male or female
Age range: 20 years of age or older
Disease status: diagnosis of osteoporosis based on either a T-score of less than or equal to -2.5 SD on bone densitometry or minimal trauma fracture.
Must meet the PBS authority criteria for bisphosphonate therapy.
Concomitant disease status: immunocompetent
Laboratory parameters: eGFR equal to or more than 30
Willingness to give written or informed consent and willingness to participate to and comply with the study.
Minimum age
20 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study.
Laboratory parameters: eGFR < 30
Patients who have received previous anti-resorptive therapy.
Patients with dental issues requiring extraction or intervention involving the jaw bone.
Patients unable to give informed consent.
Patients receiving medication that may interact with either prenylation or the immune system: statin therapy and immunosuppressant therapy including glucocorticoids

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/03/2014
Actual
13/03/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
44
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 2183 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 7862 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 288874 0
Other
Name [1] 288874 0
Bone Research Group
Garvan Institute Medical Research
Country [1] 288874 0
Australia
Primary sponsor type
Other
Name
Bone Research Group, Garvan Institute of Medical Research
Address
384 Victoria St
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 287568 0
None
Name [1] 287568 0
Address [1] 287568 0
Country [1] 287568 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290703 0
St Vincent's Research Office
Ethics committee address [1] 290703 0
Level 6
Delacy Building
St Vincent's Hospital
Victoria St
Darlinghurst NSW 2010
Ethics committee country [1] 290703 0
Australia
Date submitted for ethics approval [1] 290703 0
Approval date [1] 290703 0
29/08/2013
Ethics approval number [1] 290703 0
HREC/13/SVH/215

Summary
Brief summary
Osteoporosis is common in the Australian population and is a disease in which the bones lose minerals such as calcium, more quickly than the body can replace them. As a results, the bones become fragile and brittle, leading to higher risk of fractures and a loss of bone mass.
Bisphosphonates are the main drugs used in the treatment of osteoporosis and work by inhibiting bone loss. Bisphosphonates also have additional effects that are not related to preventing bone loss. These additional effects are thought to be due to their action on the immune system (the cells that fight against disease in the body).
There is no study to date showing that bisphosphonates are taken up by human immune cells and this study will enable us to examine the impact these medications have on the human immune system.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 46878 0
A/Prof Jackie Center
Address 46878 0
Level 5,
Garvan Institute
384 Victoria St
Darlinghurst NSW 2010
Country 46878 0
Australia
Phone 46878 0
+61 (02) 9295 8106
Fax 46878 0
Email 46878 0
[email protected]
Contact person for public queries
Name 46879 0
Dr Chelsea McMahon
Address 46879 0
Level 5,
Garvan Institute
384 Victoria St
Darlinghurst NSW 2010
Country 46879 0
Australia
Phone 46879 0
+61 (02) 9295 8106
Fax 46879 0
Email 46879 0
[email protected]
Contact person for scientific queries
Name 46880 0
Prof Mike Rogers
Address 46880 0
Level 5,
Garvan Institute
384 Victoria St
Darlinghurst NSW 2010
Country 46880 0
Australia
Phone 46880 0
+61 (02) 9295 8273
Fax 46880 0
Email 46880 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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