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

February 8, 2010 updated by: Monash University

Randomised Controlled Trial of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease: A Pilot Study

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Department of Nephrology, Monash Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 2
Placebo
Drug: Placebo
weekly orally
Active Comparator: 1
Alendronate
Drug: Alendronate
70mg weekly orally
Other Names:
  • Fosamax

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in degree of arterial stiffness measured by pulse wave velocity
Time Frame: 18 months
18 months
Changes in vascular calcification on CT scans of superficial femoral artery and aorta
Time Frame: 18 months
18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in bone mineral density
Time Frame: 18 months
18 months
Changes in serum calcium and phosphate levels
Time Frame: 18 months
18 months
Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD
Time Frame: 18 months
18 months
Incidence of fractures
Time Frame: 18 months
18 months
Symptoms and severity of side effects from alendronate
Time Frame: 18 months
18 months
Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L)
Time Frame: 18 months
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Monash University

Investigators

  • Principal Investigator: Peter G Kerr, MBBS FRACP, Monash Medical Centre, Clayton, Victoria, Australia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (Actual)

September 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

November 1, 2006

First Submitted That Met QC Criteria

November 1, 2006

First Posted (Estimate)

November 2, 2006

Study Record Updates

Last Update Posted (Estimate)

February 9, 2010

Last Update Submitted That Met QC Criteria

February 8, 2010

Last Verified

February 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HREC 06099C

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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