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

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ClinicalTrials.gov Identifier: NCT00395382
Recruitment Status : Completed
First Posted : November 2, 2006
Last Update Posted : February 9, 2010
Sponsor:
Information provided by:
Monash University

Tracking Information
First Submitted Date  ICMJE November 1, 2006
First Posted Date  ICMJE November 2, 2006
Last Update Posted Date February 9, 2010
Study Start Date  ICMJE January 2007
Actual Primary Completion Date September 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2009)
  • Change in degree of arterial stiffness measured by pulse wave velocity [ Time Frame: 18 months ]
  • Changes in vascular calcification on CT scans of superficial femoral artery and aorta [ Time Frame: 18 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 1, 2006)
  • Change in degree of arterial stiffness measured by pulse wave velocity
  • Changes in vascular calcification on CT scans of superficial femoral artery and aorta
Change History Complete list of historical versions of study NCT00395382 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2009)
  • Changes in bone mineral density [ Time Frame: 18 months ]
  • Changes in serum calcium and phosphate levels [ Time Frame: 18 months ]
  • Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD [ Time Frame: 18 months ]
  • Incidence of fractures [ Time Frame: 18 months ]
  • Symptoms and severity of side effects from alendronate [ Time Frame: 18 months ]
  • Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L) [ Time Frame: 18 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2006)
  • Changes in bone mineral density
  • Changes in serum calcium and phosphate levels
  • Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD
  • Incidence of fractures
  • Symptoms and severity of side effects from alendronate
  • Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease
Official Title  ICMJE Randomised Controlled Trial of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease: A Pilot Study
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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Vascular Calcification
  • Arteriosclerosis
Intervention  ICMJE
  • Drug: Alendronate
    70mg weekly orally
    Other Name: Fosamax
  • Drug: Placebo
    weekly orally
Study Arms  ICMJE
  • Active Comparator: 1
    Alendronate
    Intervention: Drug: Alendronate
  • Placebo Comparator: 2
    Placebo
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: November 1, 2006)
50
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2009
Actual Primary Completion Date September 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00395382
Other Study ID Numbers  ICMJE HREC 06099C
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr Nigel Toussaint, Department of Nephrology, Monash Medical Centre, Clayton, Australia
Study Sponsor  ICMJE Monash University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter G Kerr, MBBS FRACP Monash Medical Centre, Clayton, Victoria, Australia
PRS Account Monash University
Verification Date February 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP