Queen's University Investigation of Calcification in Chronic Kidney Disease

Study Overview
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Brief Summary
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Kidney disease is a fundamental part of medicine because of its prominence in Western society. Common conditions such as diabetes, hypertension and kidney infections can all progress to End-Stage Renal Disease (ESRD) also known as Stage 5 chronic kidney disease (CKD 5). Once ESRD has begun, kidney function is poor at best, thus the body is unable to effectively clear harmful toxins from the blood. A common feature of ESRD is vascular calcification, a process where blood vessels (especially arteries) attract deposits of the mineral calcium. Over time, these deposits harden and thicken in the layers of blood vessels, which limit blood flow to body tissues and can produce significant disease including hypertension, heart disease and stroke. Although the process of vascular calcification is unknown, there is mounting evidence that it is mediated by cellular events that are similar to those seen in bone formation with in the body (osteogenesis). With this point in mind, it has been suggested that agents medicine employs to limit excess bone formation will reduce the rate of vascular calcification in CKD Stage 5. This study will employ one group of drugs called bisphosphonates which have been used to limit bone formation. It will study their effect on vascular calcification in adult dialysis patients.

Detailed Description
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Presently, there exist few therapies aimed at retarding the progression of vascular calcification. One study showed that agents that limit the absorption of phosphate from food (phosphate binders) slow the progression of vascular calcification, and as a result, treatments emphasize phosphate control through diet and phosphate binders. Other studies have shown that the use of statins, to lower LDL cholesterol levels may reduce the progression of coronary calcification in non-ESRD patients, but data from ESRD are lacking. While these treatments have been helpful, the improvements in patients' outcomes have not been overwhelming positive. This proposed study is not the first to study the use of bisphosphonates on vascular calcification. Repeated studies have shown impressive reduction in calcification rates in several animal models, which begs the question, how will bisphosphonates fare in human subjects? Preliminary research has begun, but clearly an expansive trial on humans is needed to explore the use of a promising therapy. Our study hopes to provide insight into this area of cardiovascular research.

Official Title
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The Use of Bisphosphonates to Prevent or Delay the Progression of Vascular Calcification in End-Stage Renal Disease: A Randomized Controlled Trial

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Bisphosphonate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age receiving maintenance renal replacement therapy for less than 12 months incident patients starting renal replacement therapy for the first time Exclusion Criteria: active vasculitis severe hypocalcemia previous adverse side effect to bisphosphonate use current use of corticosteroids weight greater than 300 pounds pregnancy not expected to survive greater than one year expected to discontinue renal replacement therapy during the study period or recover renal function evidence of adynamic bone disease current bisphosphonate use

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Arm #1 will include patients randomized to receive bisphosphonate therapy for 24 months. | Drug: Bisphosphonate<br>* 35mg given orally once weekly for 24 months<br>* Other names: Residronate;|
| Placebo Comparator: 2<br>Arm #2 will include patients randomized to receive placebo therapy for 24 months | Drug: Placebo<br>* identical placebo pill once weekly for 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in coronary artery calcification score (CaSc) from baseline to study completion. |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bone density score (wrist/hip) as calculated by Ct scanning method, # fractures, MI, Stroke, amputation/surgery for peripheral revascularization. |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Failure, Vascular Calcification, Bisphosphonates