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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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]

HREC 06099C

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Vascular Calcification

Arteriosclerosis

Condition category

Condition code

Renal and Urogenital

Kidney disease

Renal and Urogenital

Other renal and urogenital disorders

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Metabolic and Endocrine

Metabolic disorders

Metabolic and Endocrine

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]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Change in degree of arterial stiffness measured by pulse wave velocity

Timepoint [1]

18 months

Primary outcome [2]

Changes in vascular calcification on CT scans of superficial femoral artery and aorta

Timepoint [2]

18 months

Secondary outcome [1]

Changes in bone mineral density

Timepoint [1]

18 months

Secondary outcome [2]

Changes in serum calcium and phosphate levels

Timepoint [2]

18 months

Secondary outcome [3]

Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD

Timepoint [3]

18 months

Secondary outcome [4]

Incidence of fractures

Timepoint [4]

18 months

Secondary outcome [5]

Symptoms and severity of side effects from alendronate

Timepoint [5]

18 months

Secondary outcome [6]

Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L)

Timepoint [6]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Department of Nephrology, Monash Medical Centre - Clayton

Recruitment postcode(s) [1]

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/study/NCT00395382

Trial related presentations / publications

Hara T, Hijikata Y, Matsubara Y, Watanabe N. Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD013424. doi: 10.1002/14651858.CD013424.pub2.
Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG. Using vertebral bone densitometry to determine aortic calcification in patients with chronic kidney disease. Nephrology (Carlton). 2010 Aug;15(5):575-83. doi: 10.1111/j.1440-1797.2010.01288.x.

Public notes

Contacts

Principal investigator

Name

Peter G Kerr, MBBS FRACP

Address

Monash Medical Centre, Clayton, Victoria, Australia

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

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

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT00395382

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Trial Review

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