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

Phase 2

Completed

• Conditions: Liver Transplantation; Bone Resorption; Heart Transplantation
• Interventions: Drug: Zoledronic acid; Drug: Alendronate; Other: Placebo Alendronate; Other: Placebo Zoledronic Acid

• Registration Number: NCT00297830
• Lead Sponsor: Columbia University

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.

Study Timeline

• Study Start: 2005-11
• Study First Submitted: 2006-02-27
• Study First Submitted QC: 2006-02-27
• Study First Posted: 2006-03-01
• Primary Completion: 2010-04
• Results First Submitted: 2013-02-15
• Study Completion: 2014-01
• Results First Submitted QC: 2016-07-28
• Results First Posted: 2016-09-15
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-18
• Last Update Posted: 2018-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 111

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Zoledronic Acid & Placebo Alendronate	Placebo Alendronate	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.
Placebo Zoledronic Acid & Active Alendronate	Placebo Zoledronic Acid	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.
Active Zoledronic Acid & Placebo Alendronate	Zoledronic acid	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.
Placebo Zoledronic Acid & Active Alendronate	Alendronate	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.

Primary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 12 Months	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months	Baseline, 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.
Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 12 Months	Baseline, 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.
Serum N-telopeplide Percent Change	24 months

Trial Locations

Locations (1)

Columbia University Medical Center; 🇺🇸 New York, New York, United States