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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00395382




Registration number
NCT00395382
Ethics application status
Date submitted
1/11/2006
Date registered
2/11/2006
Date last updated
9/02/2010

Titles & IDs
Public title
Study of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease
Scientific title
Randomised Controlled Trial of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease: A Pilot Study
Secondary ID [1] 0 0
HREC 06099C
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vascular Calcification 0 0
Arteriosclerosis 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Alendronate
Treatment: Drugs - Placebo

Active Comparator: 1 - Alendronate

Placebo Comparator: 2 - Placebo


Treatment: Drugs: Alendronate
70mg weekly orally

Treatment: Drugs: Placebo
weekly orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in degree of arterial stiffness measured by pulse wave velocity
Timepoint [1] 0 0
18 months
Primary outcome [2] 0 0
Changes in vascular calcification on CT scans of superficial femoral artery and aorta
Timepoint [2] 0 0
18 months
Secondary outcome [1] 0 0
Changes in bone mineral density
Timepoint [1] 0 0
18 months
Secondary outcome [2] 0 0
Changes in serum calcium and phosphate levels
Timepoint [2] 0 0
18 months
Secondary outcome [3] 0 0
Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD
Timepoint [3] 0 0
18 months
Secondary outcome [4] 0 0
Incidence of fractures
Timepoint [4] 0 0
18 months
Secondary outcome [5] 0 0
Symptoms and severity of side effects from alendronate
Timepoint [5] 0 0
18 months
Secondary outcome [6] 0 0
Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L)
Timepoint [6] 0 0
18 months

Eligibility
Key inclusion criteria
- Subjects with CKD Stage 3 (GFR between 30 and 59ml/min)

- Subjects must be 18 years of age or older

- Willingness to provide written informed consent
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects unable to give informed consent or whom have an expected life-span of less
than 3 months

- Subjects undertaking renal replacement therapy (dialysis or transplantation)

- Subjects already taking bisphosphonates

- Subjects with recent fracture (within the last 3 months)

- Subjects scheduled to have a kidney transplant from a known living donor

- Subjects with active gastro-oesophageal reflux disease or peptic ulcer disease

- Subjects who are pregnant or planning on becoming pregnant in the next 18 months

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering 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
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2009
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Department of Nephrology, Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton

Funding & Sponsors
Primary sponsor type
Other
Name
Monash University
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Cardiovascular disease (CVD) is the commonest cause of mortality in patients with chronic
kidney disease (CKD) and end-stage kidney disease (ESKD). Reasons for the greater incidence
of CVD in this group include traditional CVD risk factors of hypertension, dyslipidemia and
diabetes but more importantly also include non-traditional risk factors such as calcium and
phosphate imbalance. The latter is thought most likely to contribute to vascular
calcification, especially for those on dialysis, and this in turn leads to arterial stiffness
and left ventricular hypertrophy, the two commonest cardiovascular complications. Arterial
stiffness and calcification have been found to be independent predictors of all-cause and
cardiovascular mortality in CKD. Few studies, though, have looked at both structural and
functional changes associated with calcification and there have been very few interventional
studies addressing this issue.

Control of calcium and phosphate levels in CKD can occur with the use of medications that
reduce elevated serum phosphate (phosphate binders, mostly calcium-based) and those to treat
hyperparathyroidism (vitamin D and more recently calcium sensing receptor agonists called
calcimimetics). These pharmacological managements addressing calcium and phosphate imbalance
reduce vascular calcification and CVD. Bisphosphonate therapy may also have a role in
reduction of calcification.

Low bone mineral density (BMD) is common in CKD patients and predicts increased fracture risk
similar to the general population. Bisphosphonate therapy improves BMD and lowers the
fracture risk. Bisphosphonates may also have a role in secondary hyperparathyroidism to
reduce hypercalcemia and allow for more aggressive calcitriol treatment. Recent studies have
addressed the possibility of bisphosphonates reducing the progression of vascular
calcification in CKD and revealed that the extent of calcification may be suppressed in
association with a reduction in chronic inflammatory responses.

The investigators aim to perform a prospective, randomised study assessing the impact of
alendronate on cardiovascular and bone mineral parameters. This will be a single-centre study
involving subjects with CKD Stage 3 (those patients with GFR between 30 and 59ml/min).
Arterial stiffness (by pulse wave analysis and pulse wave velocity) and vascular
calcification (using CT scans through superficial femoral artery) will be followed as well as
serum markers of calcium, phosphate and PTH. Differences in these end-points will be compared
between participants taking alendronate and those not. The study will be conducted over a 12
month period and the investigators aim to recruit about 50 patients (25 on alendronate and 25
control).
Trial website
https://clinicaltrials.gov/ct2/show/NCT00395382
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peter G Kerr, MBBS FRACP
Address 0 0
Monash Medical Centre, Clayton, Victoria, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00395382