NCT00395382

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jan 2007

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 1, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 2, 2006

Completed
2 months until next milestone

Study Start

First participant enrolled

January 1, 2007

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2009

Completed
Last Updated

February 9, 2010

Status Verified

February 1, 2010

Enrollment Period

2.7 years

First QC Date

November 1, 2006

Last Update Submit

February 8, 2010

Conditions

Vascular CalcificationArteriosclerosis

Keywords

Vascular calcificationArterial stiffnessCardiovascular riskBone mineral metabolismCalcium

Outcome Measures

Primary Outcomes (2)

  • Change in degree of arterial stiffness measured by pulse wave velocity

    18 months

  • Changes in vascular calcification on CT scans of superficial femoral artery and aorta

    18 months

Secondary Outcomes (6)

  • Changes in bone mineral density

    18 months

  • Changes in serum calcium and phosphate levels

    18 months

  • Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD

    18 months

  • Incidence of fractures

    18 months

  • Symptoms and severity of side effects from alendronate

    18 months

  • +1 more secondary outcomes

Study Arms (2)

1

ACTIVE COMPARATOR

Alendronate

Drug: Alendronate

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

AlendronateDRUG

70mg weekly orally

Also known as: Fosamax
1
PlaceboDRUG

weekly orally

2

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Nephrology, Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Related Publications (2)

  • 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.

    PMID: 34231877DERIVED

  • 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.

    PMID: 20649879DERIVED

MeSH Terms

Conditions

Vascular CalcificationArteriosclerosis

Interventions

Alendronate

Condition Hierarchy (Ancestors)

CalcinosisCalcium Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesArterial Occlusive DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

DiphosphonatesOrganophosphonatesOrganophosphorus CompoundsOrganic Chemicals

Study Officials

  • Peter G Kerr, MBBS FRACP

    Monash Medical Centre, Clayton, Victoria, Australia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

November 1, 2006

First Posted

November 2, 2006

Study Start

January 1, 2007

Primary Completion

September 1, 2009

Study Completion

September 1, 2009

Last Updated

February 9, 2010

Record last verified: 2010-02

Locations

AU(1)