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

This study has been completed.
Sponsor:
Information provided by:
Monash University
ClinicalTrials.gov Identifier:
NCT00395382
First received: November 1, 2006
Last updated: February 8, 2010
Last verified: February 2010
  Purpose

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 Intervention Phase
Vascular Calcification
Arteriosclerosis
Drug: Alendronate
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Monash University:

Primary Outcome Measures:
  • Change in degree of arterial stiffness measured by pulse wave velocity [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Changes in vascular calcification on CT scans of superficial femoral artery and aorta [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in bone mineral density [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Changes in serum calcium and phosphate levels [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Incidence of fractures [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Symptoms and severity of side effects from alendronate [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: January 2007
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Alendronate
Drug: Alendronate
70mg weekly orally
Other Name: Fosamax
Placebo Comparator: 2
Placebo
Drug: Placebo
weekly orally

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00395382

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

No publications provided by Monash University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Nigel Toussaint, Department of Nephrology, Monash Medical Centre, Clayton, Australia
ClinicalTrials.gov Identifier: NCT00395382     History of Changes
Other Study ID Numbers: HREC 06099C
Study First Received: November 1, 2006
Last Updated: February 8, 2010
Health Authority: Australia: Human Research Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Monash University:
Vascular calcification
Arterial stiffness
Cardiovascular risk
Bone mineral metabolism
Calcium

Additional relevant MeSH terms:
Arteriosclerosis
Calcinosis
Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Urologic Diseases
Renal Insufficiency
Alendronate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014