Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the effectiveness and safety of zoledronic acid with alendronate in the prevention of bone loss after organ transplantation. Zoledronic acid is given as a single intravenous infusion. Alendronate is given as a weekly pill. Both are expected to be very effective, but it is not known which one will work best.

Detailed Description
-----------------
Patients who have undergone heart or liver transplantation are usually required to remain on medications, such as Prednisone and Cyclosporine A or Tacrolimus, that prevent the body from rejecting the transplanted organ. These medications may cause bone loss which leads to thinning of the bones (osteoporosis) and therefore greatly increase the risk of having broken bones (fractures) after transplantation. Several published studies have shown that 14% to 35% of heart transplant patients develop fractures (spine, ribs and hip) during the first year after transplantation. We have previously shown that alendronate (Fosamax), a drug approved by the FDA for prevention and treatment of postmenopausal osteoporosis and prednisone-induced osteoporosis, prevents bone loss after heart transplantation. We are conducting this study to determine whether a newer drug, zoledronic acid, is as effective as alendronate. This study is a randomized, double-blind, placebo-controlled 2-year study. Participants will receive one dose of active zoledronic acid during the first month after heart or liver transplantation and weekly placebo alendronate pills or one dose of placebo zoledronic acid and weekly active alendronate pills for the first year after transplant. Over 2 years, participants will provide blood samples on nine occasions. Bone density will be performed 4-5 times and spine xrays will be performed twice.

Official Title
-----------------
Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation

Conditions
-----------------
Heart Transplantation, Liver Transplantation, Bone Resorption

Intervention / Treatment
-----------------
* Drug: Zoledronic acid
* Drug: Alendronate
* Other: Placebo Zoledronic Acid
* Other: Placebo Alendronate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A man or woman, aged 20 to 70, of any race who has had a heart or liver transplant Exclusion Criteria: hyperparathyroidism Paget's disease hyperthyroidism cancer severe kidney disease, intestinal disease active peptic ulcer disease current or past treatment for osteoporosis pregnancy or lactation severe oral/dental disease

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Zoledronic Acid & Placebo Alendronate<br>Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion. | Drug: Zoledronic acid<br>* Drug is administered through 5 mg intravenous infusion over 20 minutes<br>* Other names: Zometa;Other: Placebo Alendronate<br>* Placebo alendronate 70 mg once weekly<br>|
| Experimental: Placebo Zoledronic Acid & Active Alendronate<br>Group 2 will receive an infusion of placebo zoledronic acid during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion. | Drug: Alendronate<br>* Alendronate 70 mg will be taken once a week in the morning at least 30-60 minutes before first meal<br>* Other names: Fosamax;Other: Placebo Zoledronic Acid<br>* Infusion of placebo zoledronic acid during the first 5 weeks after transplantation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 12 Months | BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. | Baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. | Baseline, 12 months | 
| Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 12 Months | BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. | Baseline, 12 months | 
| Serum N-telopeplide Percent Change |  | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart Transplantation, Liver Transplantation, Immunosuppression, Bone Density/drug effects, Alendronate, Zoledronic acid, Comparative study, Humans