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

Arteriosclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00395382
• Other study ID #: HREC 06099C
• Status: Completed
• Phase: Phase 4
• First received: November 1, 2006
• Last updated: February 8, 2010
• Start date: January 2007
• Est. completion date: September 2009

Study information

• Verified date: February 2010
• Source: Monash University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics CommitteeAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Arteriosclerosis
• Calcinosis
• Kidney Diseases
• Renal Insufficiency, Chronic
• Vascular Calcification

Intervention

Drug:
• Alendronate
70mg weekly orally
• Placebo
weekly orally

Locations

Country	Name	City	State
Australia	Department of Nephrology, Monash Medical Centre	Clayton	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Monash University

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in degree of arterial stiffness measured by pulse wave velocity		18 months	No
Primary	Changes in vascular calcification on CT scans of superficial femoral artery and aorta		18 months	No
Secondary	Changes in bone mineral density		18 months	No
Secondary	Changes in serum calcium and phosphate levels		18 months	No
Secondary	Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD		18 months	No
Secondary	Incidence of fractures		18 months	No
Secondary	Symptoms and severity of side effects from alendronate		18 months	Yes
Secondary	Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L)		18 months	Yes