Osteoporosis Prevention After Heart Transplant

NCT ID: NCT00000412

Last Updated: 2015-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 149 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-09-30
• Study Completion Date: 2002-04-30

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.

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.

Conditions

Osteoporosis; Cardiac Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Group A

Group A active alendronate (10 mg/day) and placebo calcitriol.

Group Type: ACTIVE_COMPARATOR

Alendronate

Intervention Type: DRUG

Placebo Calcitriol

Intervention Type: DRUG

Group B

We will give Group B placebo alendronate and active calcitriol (0.25 micrograms BID).

Group Type: PLACEBO_COMPARATOR

Calcitriol

Intervention Type: DRUG

Placebo Alendronate

Intervention Type: DRUG

Interventions

Alendronate

Intervention Type: DRUG

Calcitriol

Intervention Type: DRUG

Placebo Alendronate

Intervention Type: DRUG

Placebo Calcitriol

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth Shane, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University Department of Medicine

Locations

Columbai University Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Countries

United States

References

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. doi: 10.1056/NEJMoa035617.

Reference Type: BACKGROUND

PMID: 14973216 (View on PubMed)

Other Identifiers

R01AR046124

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIAMS-008

Identifier Type: OTHER

Identifier Source: secondary_id

R01AR046124

Identifier Type: NIH

Identifier Source: org_study_id

View Link