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Trial registered on ANZCTR


Registration number
ACTRN12611000507987
Ethics application status
Approved
Date submitted
20/04/2011
Date registered
16/05/2011
Date last updated
16/05/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised, double-blind, one-year controlled trial comparing Aclasta (zoledronic acid) 5 mg intravenously (i/v) against placebo infusion in patients with anti-epileptic (AED) drug induced bone loss
Scientific title
A randomised, double-blind, one-year controlled trial comparing bone mineral density following treatment with Aclasta (zoledronic acid 5mg i/v) versus placebo infusion in patients with AED-induced bone loss
Secondary ID [1] 260035 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bone loss (osteoporosis) 265693 0
Use of anti-epileptic drugs 265720 0
Condition category
Condition code
Musculoskeletal 265830 265830 0 0
Osteoporosis
Neurological 265862 265862 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
5mg dose of zoledronic acid in 100 mL solution administered intravenously at months 1 and 12 of the trial. All participants will then enter the open label extension at the 12 month visit (ie 12 months after the initial day 1 visit of the first year of the trial), where both groups will receive zoledronic acid 5mg iv at this month 12 visit only;
600 mg of elemental calcium twice daily and 1000 international units daily of vitamin D for the duration of the trial being 2 years, beginning at day 1 in oral capsule form;
Paracetamol 2x500 mg capsules every 6 hours for 3 days post each infusion.
Intervention code [1] 264454 0
Treatment: Drugs
Comparator / control treatment
Placebo 100 mL solution of sterile water supplied in ready-to-infuse plastic bottles, intravenous.
Control group
Placebo

Outcomes
Primary outcome [1] 266590 0
To assess whether lumbar spine and/or total hip BMD as measured by DXA at 1 Year in patients treated with zoledronic acid is significantly greater than in patients treated with placebo.
Timepoint [1] 266590 0
1 year
Primary outcome [2] 266739 0
Exploratory Objectives:
To compare peripheral quantitative computed tompgraphy (pQCT) (non-dominant tibia) and quantitative heel ultrasound measures in the zoledronic acid group vs. the placebo group at 1 and 2 years.
Timepoint [2] 266739 0
1 and 2 years
Secondary outcome [1] 276073 0
To evaluate the differences between treatment and placebo groups with respect to relative changes in biochemical markers of bone turnover at 1 Year, measured via serum bone markers (CTX and P1NP)
Timepoint [1] 276073 0
1 year

Eligibility
Key inclusion criteria
1)Patients taking AED in standard doses for at least 2 years
2)Bone mineral density Z score < -1.5 or T score < -2.0 (Hologic) at the lumbar spine, total hip or femoral neck; males aged 30 years or older, females postmenopausal and aged 50 years or older.
3)Patients must be on a stable course of epileptic therapy and have stable disease at the time of screening (in the opinion of the treating epilepsy specialist).
Minimum age
30 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1)Prevalent major low-trauma fractures
2)Other secondary causes of osteoporosis/fractures
3)Limited life expectancy
4)Contraindications to i/v bisphosphonates
5)Prior use of tibolone or raloxifene within the last 6 months
6)Any prior use of PTH or sodium fluoride for more than 1 week; if used for < 1 week, washout period for PTH or sodium fluoride 6 months
7)Prior exposure to anabolic steroids or growth hormone within 6 months of entry in the trial
8)Prior use of strontium ranelate within 1 year
9)Creatinine clearance < 35 ml/min
10)Pre-existing hypocalcemia (must be treated by adequate intake of calcium and vitamin D before therapy with zoledronic acid)
11)Active history of uveitis, iritis, or episcleritis
12)Metastatic cancer or cancer diagnosed less than 2 years ago where treatment is still ongoing
13)History of diabetes mellitus
14)Active primary hyperparathyroidism or other metabolic bone disorder
15)Hypothyroidism, not appropriately controlled with long-term thyroxine therapy
16)Serum 25-hydroxyvitamin D concentrations < 50 nmol/L (may be re-assessed for inclusion after adequate vitamin D repletion)
17) Any bisphosphonate therapy within the prior 2 years, except oral bisphosphonate for up to 2 weeks in total in the previous 2 years.
18) Women of childbearing potential not using an effective contraception method as well as women who are breastfeeding
19) Known sensitivity to study drug or class of study drug
20) Patients with any severe medical condition(s) that in the view of the investigator prohibits participation in the study (specify as required)
21)Use of any other investigational agent in the last 30 days
22)Unable for any reason to complete the specified assessments to at least 12 months
23) Inability to measure areal BMD at both the lumbar spine and at least one hip
24)Current treatment with topiramate.

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)
All participants will be screened to determine eligibility. At the second visit (‘day 1’) all eligible patients will be assigned to one of the treatment groups. Patients will be randomized to receive either zoledronic acid or placebo in a 1:1 ratio, stratified for therapy at baseline: Liver enzyme inducer/ valproate/ other liver enzyme non-inducer (in case of polytherapy, taking any inducer would put patient in inducer group; similarly, taking valproate would put patient in valproate group unless also on an inducer).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be stratified by investigator staff (based on AED/s taken) and patients will be assigned treatment using the following procedure to ensure that treatment assignment is unbiased and concealed from patients and investigator staff. A randomization list will be produced by an independent statistician using a system that ensures the random assignment of treatment groups in the specified ratio and balanced in each stratum. The computerised program used to generate the random sequence is STATA add-on, based on a seed number.
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/05/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 264940 0
Commercial sector/Industry
Name [1] 264940 0
Novartis Pharmaceuticals Australia Pty Limited
Country [1] 264940 0
Australia
Primary sponsor type
Hospital
Name
Melbourne Health
Address
Melbourne Health
c/- Department of Medicine (RMH/WH)
L4, Clinical Sciences Building
Royal Parade
Parkville VIC 3050
Country
Australia
Secondary sponsor category [1] 264038 0
None
Name [1] 264038 0
Address [1] 264038 0
Country [1] 264038 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266898 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 266898 0
C/- The Post Office
The Royal Melbourne Hospital
Grattan Street
Parkville VIC 3050
Ethics committee country [1] 266898 0
Australia
Date submitted for ethics approval [1] 266898 0
01/10/2010
Approval date [1] 266898 0
03/02/2011
Ethics approval number [1] 266898 0
2010.233

Summary
Brief summary
The purpose of this study is to investigate whether Aclasta is effective in treating osteoporosis caused by AED use.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32517 0
Address 32517 0
Country 32517 0
Phone 32517 0
Fax 32517 0
Email 32517 0
Contact person for public queries
Name 15764 0
Alicia Seymour
Address 15764 0
Department of Medicine (RMH/WH)
Level 4 Clinical Sciences Building
The Royal Melbourne Hospital
Royal Parade
Parkville VIC 3050
Country 15764 0
Australia
Phone 15764 0
+61 3 8344 3248
Fax 15764 0
+61 3 9348 2254
Email 15764 0
[email protected]
Contact person for scientific queries
Name 6692 0
Professor John Wark
Address 6692 0
Department of Medicine (RMH/WH)
Level 4 Clinical Sciences Building
The Royal Melbourne Hospital
Royal Parade
Parkville VIC 3050
Country 6692 0
Australia
Phone 6692 0
+61 3 8344 5201
Fax 6692 0
Email 6692 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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