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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00395382
Recruitment Status : Completed
First Posted : November 2, 2006
Last Update Posted : February 9, 2010
Information provided by:
Monash University

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).

Condition or disease Intervention/treatment Phase
Vascular Calcification Arteriosclerosis Drug: Alendronate Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomised Controlled Trial of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease: A Pilot Study
Study Start Date : January 2007
Actual Primary Completion Date : September 2009
Actual Study Completion Date : September 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 1
Drug: Alendronate
70mg weekly orally
Other Name: Fosamax

Placebo Comparator: 2
Drug: Placebo
weekly orally

Primary Outcome Measures :
  1. Change in degree of arterial stiffness measured by pulse wave velocity [ Time Frame: 18 months ]
  2. Changes in vascular calcification on CT scans of superficial femoral artery and aorta [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. Changes in bone mineral density [ Time Frame: 18 months ]
  2. Changes in serum calcium and phosphate levels [ Time Frame: 18 months ]
  3. Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD [ Time Frame: 18 months ]
  4. Incidence of fractures [ Time Frame: 18 months ]
  5. Symptoms and severity of side effects from alendronate [ Time Frame: 18 months ]
  6. Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L) [ Time Frame: 18 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00395382

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Australia, Victoria
Department of Nephrology, Monash Medical Centre
Clayton, Victoria, Australia, 3168
Sponsors and Collaborators
Monash University
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Principal Investigator: Peter G Kerr, MBBS FRACP Monash Medical Centre, Clayton, Victoria, Australia

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Dr Nigel Toussaint, Department of Nephrology, Monash Medical Centre, Clayton, Australia Identifier: NCT00395382     History of Changes
Other Study ID Numbers: HREC 06099C
First Posted: November 2, 2006    Key Record Dates
Last Update Posted: February 9, 2010
Last Verified: February 2010
Keywords provided by Monash University:
Vascular calcification
Arterial stiffness
Cardiovascular risk
Bone mineral metabolism
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Vascular Calcification
Urologic Diseases
Renal Insufficiency
Calcium Metabolism Disorders
Metabolic Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Bone Density Conservation Agents
Physiological Effects of Drugs