Ibandronate Versus Placebo in the Prevention of Bone Loss After Renal Transplantation.

Study Overview
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Brief Summary
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Loss of bone mass is a common complication in patients with end-stage-renal failure, both before and particularly after transplantation. In addition to standard underlying therapy with calcium and active vitamin D, we will study the effect of ibandronate (a bisphosphonate) versus placebo on bone mineral density as well as incidence of fracture rates after kidney transplantation.We also wish to study whether any prevented bone loss will also lead to reduced cardiovascular disease. Patients will be followed for 12 months after transplantation, and the ibandronate treatment is one injection every 3 months.

Detailed Description
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Demographic, medical history, previous and current medication, as well as baseline measurements of Bone Mineral Density (BMD), laboratory efficacy and safety variables as well as Quality-of-Life scores will be undertaken in the period from 1 week prior to transplantation until 1 week after transplantation. In this period, any existing fractures will be determined using traditional x-ray of the thoraco-lumbar columna. Renal graft functioning as well as transplantation complications will be followed tightly, and calcium supplementation as well as active vitamin D (calcitriol) will be administered together with the standard immunosuppressive regimen. As soon as patients have recovered from transplantation, and renal functioning is considered sufficiently stable, and no later than 28 days after the transplantation, qualified patients will be randomised to receive either ibandronate or placebo, stratified by gender. Bone mineral density and most of the clinical data and laboratory tests will then be followed until 12 months after transplantation as described in the attached flowchart (section 11.1), with hospital visits for administration of study drugs and follow-up of at 13, 26, 39 and 52 weeks after transplantation. Furthermore, all the patients will be followed prospectively from the time of transplantation and for ten years with regard to cardiovascular events. Data concerning cardiovascular events will be collected from the Norwegian renal registry for the whole study population in the follow up period of about 10 years.

Official Title
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Ibandronate Versus Placebo as add-on to Active Vitamin D and Calcium in the Prevention of Bone Loss After Renal Transplantation.

Conditions
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Renal Transplant

Intervention / Treatment
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* Drug: Placebo
* Drug: Ibandronate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant recipients Adults, ≥ 18 years of age Either gender Signed informed consent Exclusion Criteria: Persisting s-Ca > 2.55 mmol/L (through the first two weeks after transplantation) Impaired graft functioning (estimated GFR <30 ml/min) Previous (within the last 12 months) treatment with bisphosphonates, sodium fluoride, calcitonin, strontium, PTH, SERM, growth hormone or anabolic steroids at any time before transplantation. Known adynamic bone disease Previous parathyroidectomy Pregnant or lactating females or females of childbearing potential who do not use an approved method of contraception (oral contraceptives or IUD); positive urine pregnancy test, where applicable. Use of any investigational drug (s) and/or device(s) Previous participation in this trial History of hypersensitivity to bisphosphonates

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Ibandronate | Drug: Ibandronate<br>* I.v.<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in percent lumbar BMD change from baseline to 12 months between the two treatment groups. |  | December 2010 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lumbar BMD change; absolute and relative |  | December 2010 | 
| Hip BMD change; absolute and relative |  | December 2010 | 
| Radial BMD change; absolute and relative |  | December 2010 | 
| Femural BMD change; absolute and relative |  | December 2010 | 
| Change in height |  | December 2010 | 
| Change in biochemical efficacy and bone markers |  | December 2010 | 
| Change in HRQoL scores (SF-36 and mini OQOL) |  | December 2010 | 
| Incidence of post-transplant complications |  | December 2010 | 
| Frequency of clinically significant safety laboratory variables |  | December 2010 | 
| Adverse event rates |  | December 2010 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ibandronate, Placebo, Doubleblind, Bone, loss, Kidney, transplant