Official Title: “Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation”

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.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

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.

Intervention(s) in this Clinical Trial

• Drug: zoledronic acid
  • Drug is administered through 5 mg intravenous infusion over 20 minutes
• Drug: alendronate
  • Alendronate 70 mg will be taken once a week in the morning at least 30-60 minutes before first meal

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • 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.
• Experimental: 2
  • Group 2 will receive an infusion of placebo 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 Measures

• total hip bone mineral density
  • Time Frame: 12 months
    Safety Issue?: No

Secondary Measures

• lumbar spine bone mineral density
  • Time Frame: 12 months
    Safety Issue?: No
• femoral neck bone mineral density
  • Time Frame: 12 months
    Safety Issue?: No
• serum n-telopeptide (%)
  • Time Frame: 24 months
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Columbia University

Overall Clinical Trial Officials and Contacts

Elizabeth Shane, M.D. Principal Investigator Columbia University  

Overall Contact: Halley Eisenberg, MPH 212-305-7225 hfe2101@columbia.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00297830

Study ID Number: CZOL446H104

ClinicalTrials.gov Identifier: NCT00297830

Health Authority: United States: Institutional Review Board