Study of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease

NCT ID: NCT00395382

Last Updated: 2010-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2009-09-30

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).

Conditions

Vascular Calcification; Arteriosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

1

Alendronate

Group Type: ACTIVE_COMPARATOR

Alendronate

Intervention Type: DRUG

70mg weekly orally

2

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

weekly orally

Interventions

Alendronate

70mg weekly orally

Intervention Type: DRUG

Placebo

weekly orally

Intervention Type: DRUG

Other Intervention Names

Fosamax

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Monash University

OTHER

Sponsor Role: lead

Responsible Party

Department of Nephrology, Monash Medical Centre, Clayton, Australia

Principal Investigators

Peter G Kerr, MBBS FRACP

Role: PRINCIPAL_INVESTIGATOR

Monash Medical Centre, Clayton, Victoria, Australia

Locations

Department of Nephrology, Monash Medical Centre

Clayton, Victoria, Australia

Countries

Australia

References

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.

Reference Type: DERIVED

PMID: 34231877 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20649879 (View on PubMed)

Other Identifiers

HREC 06099C

Identifier Type: -

Identifier Source: org_study_id