Clinical trial NCT00395382: Study of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease
Official title: Randomised Controlled Trial of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Vascular Calcification
Arteriosclerosis
Keywords: Vascular calcification
Arterial stiffness
Cardiovascular risk
Bone mineral metabolism
Calcium
Lead sponsor: Monash University
Sponsor class: OTHER
First posted: 2006-11-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).


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

Primary outcomes:
measure: Change in degree of arterial stiffness measured by pulse wave velocity
timeFrame: 18 months
measure: Changes in vascular calcification on CT scans of superficial femoral artery and aorta
timeFrame: 18 months
Secondary outcomes:
measure: Changes in bone mineral density
timeFrame: 18 months
measure: Changes in serum calcium and phosphate levels
timeFrame: 18 months
measure: Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD
timeFrame: 18 months
measure: Incidence of fractures
timeFrame: 18 months
measure: Symptoms and severity of side effects from alendronate
timeFrame: 18 months
measure: Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L)
timeFrame: 18 months
Other outcomes:
Locations:
city: Clayton
country: Australia
facility: Department of Nephrology, Monash Medical Centre
state: Victoria
Study officials:
affiliation: Monash Medical Centre, Clayton, Victoria, Australia
name: Peter G Kerr, MBBS FRACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.