Osteoporosis Prevention After Heart Transplant

• ClinicalTrials.gov Identifier: NCT00000412
• Recruitment Status: Completed
• First Posted: November 4, 1999
• Last Update Posted: July 7, 2015
• Sponsor: Columbia University
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Columbia University

Study Description

Brief Summary:

During the first year after a heart transplant, people often rapidly lose bone from their spine and hips. About 35 percent of people who receive heart transplants will suffer broken bones during the first year after transplantation. This study will compare the safety and effectiveness of the drug alendronate (Fosamax) and the active form of vitamin D (calcitriol) in preventing bone loss at the spine and hip after a heart transplant.

In this study, people who have had a successful heart transplant will receive either active alendronate and a "dummy pill" instead of calcitriol, or active calcitriol and a dummy pill instead of alendronate for the first year after their transplant, starting within 1 month after transplant surgery. We will measure bone density in the hip and spine at the start of the study and after 6 and 12 months, and will also check for broken bones in the spine. This research should lead to ways of preventing this crippling form of osteoporosis.

Condition or disease	Intervention/treatment	Phase
Osteoporosis; Cardiac Transplantation	Drug: Alendronate; Drug: Calcitriol; Drug: Placebo Alendronate; Drug: Placebo Calcitriol	Phase 3

Detailed Description:

We will enroll patients who have undergone cardiac transplantation into a randomized, double-blind, 12-month study of the efficacy and safety of calcitriol (Rocaltrol) and alendronate sodium (Fosamax) in the prevention of bone loss after transplantation. We will give all participants standard pre- and post-transplantation management and immunosuppressive therapy, three tablets of calcium citrate (Citracal + D, each containing 315 mg of elemental calcium and 200 IU of vitamin D), and a multivitamin providing 400 units of vitamin D daily. We will randomize participants to one of two active treatment groups within 1 month of transplantation. We will give Group A active alendronate (10 mg/day) and placebo calcitriol. We will give Group B placebo alendronate and active calcitriol (0.25 micrograms BID). The primary efficacy endpoint is the change in spine bone mineral density (BMD) during the first 6 months after transplantation. The secondary efficacy endpoint is the change in hip BMD during the first year after transplantation. We will also monitor the incidence of vertebral fracture.

We will invite eligible subjects to participate in the study. We will offer patients who elect not to participate in the therapeutic trial the opportunity to have serial BMD measurements at the same intervals as treated subjects and to be followed as untreated controls. We will continue recruitment until we have randomized a total of 146 cardiac transplant recipients. We will perform bone densitometry at randomization (unless performed within the previous month) and at 6 and 12 months. We will obtain radiographs (x-rays) at randomization and will repeat them at 12 months to detect undiagnosed vertebral fractures.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 149 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Prevention of Osteoporosis After Cardiac Transplantation
• Study Start Date: September 1997
• Actual Primary Completion Date: April 2002
• Actual Study Completion Date: April 2002

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Group A; Group A active alendronate (10 mg/day) and placebo calcitriol.	Drug: Alendronate; Drug: Placebo Calcitriol
Placebo Comparator: Group B; We will give Group B placebo alendronate and active calcitriol (0.25 micrograms BID).	Drug: Calcitriol; Drug: Placebo Alendronate

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Cardiac transplantation

Exclusion Criteria:

• Active peptic ulcer disease, gastrectomy, inflammatory bowel disease, malignancy, Paget's disease of bone, osteogenesis imperfecta, multiple myeloma, primary hyperparathyroidism, rheumatoid arthritis, Cushing's syndrome, or thyrotoxicosis
• Suppressive doses of thyroid hormone, anticonvulsant drugs, past bisphosphonate therapy, current calcitonin therapy, or fluoride therapy
• Cirrhosis, inflammatory liver disease, or nephrolithiasis
• Serum creatinine > 2.5 mg/dl

Contacts and Locations

Locations

United States, New York

Columbai University Medical Center

New York, New York, United States, 10032

Columbia University Medical Center

New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Merck Sharp & Dohme Corp.

Investigators

• Principal Investigator: Elizabeth Shane, MD; Columbia University Department of Medicine

More Information

Publications:

Shane E, Addesso V, Namerow PB, McMahon DJ, Lo SH, Staron RB, Zucker M, Pardi S, Maybaum S, Mancini D. Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation. N Engl J Med. 2004 Feb 19;350(8):767-76.

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT00000412 History of Changes
• Other Study ID Numbers: R01AR046124 ( U.S. NIH Grant/Contract ); R01AR046124 ( U.S. NIH Grant/Contract ); NIAMS-008 ( Other Identifier: NIAMS )
• First Posted: November 4, 1999
• Last Update Posted: July 7, 2015
• Last Verified: July 2015

Keywords provided by Columbia University:

Osteoporosis; Osteopenia; Heart transplant; Bone fracture; Bone density; Dual energy x-ray absorptiometry

Additional relevant MeSH terms:

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Alendronate; Calcitriol; Bone Density Conservation Agents; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Calcium Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Vasoconstrictor Agents; Vitamins; Micronutrients; Nutrients; Growth Substances