Study of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease
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 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|
- 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 ]
- 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 ]
|Study Start Date:||January 2007|
|Study Completion Date:||September 2009|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
Active Comparator: 1
70mg weekly orally
Other Name: Fosamax
Placebo Comparator: 2
Please refer to this study by its ClinicalTrials.gov identifier: NCT00395382
|Department of Nephrology, Monash Medical Centre|
|Clayton, Victoria, Australia, 3168|
|Principal Investigator:||Peter G Kerr, MBBS FRACP||Monash Medical Centre, Clayton, Victoria, Australia|