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

This study has been completed.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Elizabeth Shane, Columbia University
ClinicalTrials.gov Identifier:
NCT00297830
First received: February 27, 2006
Last updated: July 28, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Heart Transplantation
Liver Transplantation
Bone Resorption
Drug: Zoledronic acid
Drug: Alendronate
Other: Placebo Zoledronic Acid
Other: Placebo Alendronate
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 12 Months [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    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:
  • Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment: 111
Study Start Date: November 2005
Study Completion Date: January 2014
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active Zoledronic Acid & 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.
Drug: Zoledronic acid
Drug is administered through 5 mg intravenous infusion over 20 minutes
Other Name: Zometa
Other: Placebo Alendronate
Placebo alendronate 70 mg once weekly
Experimental: Placebo Zoledronic Acid & Active 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.
Drug: Alendronate
Alendronate 70 mg will be taken once a week in the morning at least 30-60 minutes before first meal
Other Name: Fosamax
Other: Placebo Zoledronic Acid
Infusion of placebo zoledronic acid during the first 5 weeks after transplantation

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.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00297830

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Novartis Pharmaceuticals
Investigators
Principal Investigator: Elizabeth Shane, M.D. Columbia University
  More Information

Publications:
Responsible Party: Elizabeth Shane, Professor of Medicine, Endocrinology, Columbia University
ClinicalTrials.gov Identifier: NCT00297830     History of Changes
Other Study ID Numbers: AAAB2324  CZOL446H104 
Study First Received: February 27, 2006
Results First Received: February 15, 2013
Last Updated: July 28, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Columbia University:
Heart Transplantation
Liver Transplantation
Immunosuppression
Bone Density/drug effects
Alendronate
Zoledronic acid
Comparative study
Humans

Additional relevant MeSH terms:
Bone Resorption
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Diphosphonates
Alendronate
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 05, 2016