Zoledronic Acid for the Prevention of Bone Loss Post-bone Marrow Transplantation for Thalassemia Major Patients

Zoledronic Acid for the Prevention of Bone Loss Post-bone Marrow Transplantation for Thalassemia Major Patients: A Prospective Pilot Study

This is prospective randomized, double blind study designed to evaluate the use of zoledronic acid in the prevention prevention of bone loss post allogenic BMT done for beta-thalassemia major patients.

Study Overview

• Status: Unknown
• Conditions: Bone Marrow Transplantation; Beta-Thalassemia
• Intervention / Treatment: Drug: Placebo; Drug: Zoledronic acid

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 14114
    • Hematology-Oncology & SCT Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed written informed consent.
• Patients must be 18 years old and over.
• Diagnosed with beta-thalassemia major
• Scheduled for allogenic bone marrow transplantation
• The date of randomization must be no more than 1 week after BMT.
• Patients must be accessible for follow-up.
• Life expectancy of at least 12 months from randomization.

Exclusion Criteria:

• Patients with any clinical or radiological evidence of existing fracture in the lumbar spine and/or total hip.
• Patients with a history of fracture with low-density or no associated trauma.
• Osteoporotic patients with T-score <= -2.5
• Previous treatment with a bisphosphonate.
• Patients with abnormal renal function as evidenced by either a serum creatinine determination 1.5 x or greater above the upper limit of normal or by a calculated creatinine clearance of 30 ml/minute or less.
• Pregnancy and lactation.
• Women of childbearing potential not on a medically recognized form of contraception.
• Subjects who, in the opinion of the investigator, are unlikely to cooperate fully during the study.
• Subjects participating simultaneously in studies with unapproved drugs, indications or treatment regimens.
• Known hypersensitivity to zoledronic acid or bisphosphonates.
• Patients with prior exposure to anabolic steroids, growth hormone, Parathyroid Hormone (PTH) or other drugs known to affect the skeleton (e.g., calcitonin, mithramycin, or gallium nitrate).
• Serious intercurrent illness
• History of metabolic bone diseases
• History of corticosteroid treatment for other causes
• History of antiepileptic drug treatment
• History or surgery at the lumbosacral spine, with or without implantable devices.
• Any disease of the spine that would preclude the proper acquisition of a lumbar spine DXA.
• Mental illness that precludes the patient from giving informed consent.
• Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
• Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Patients in this arm received zoledronic acid.	Drug: Zoledronic acid; Zoledronic acid 4 mg adjusted dose based on renal function IV 15-minute infusion every 3 months for a total of one year ( 4 doses ) beginning as soon as possible after randomization.; Other Names: Zometa
Placebo Comparator: Control; Patients in this arm received placebo as control group	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To describe the percent change in the lumbar spine (L1 to L4) BMD, as measured by dual energy X-ray absorptiometry, at 12 months in patients with beta-thalassemia major undergoing allogenic BMT randomized to zoledronic acid versus placebo.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
To describe the percent change in total hip BMD at 12 months in the two study arms.	1 year
To compare the changes in bone turn over markers at 3, 6, and 12 months in the two treatment arms.	1 year
To describe the incidence rate of all clinical fractures at 1 year in the two study arms.	1 year
To describe the general safety of zoledronic acid.	1 year
To describe the percent change in lumbar spine (L1 to L4) BMD and total hip BMD at 6 months when available.	1 year

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Collaborators: Novartis

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Anticipated): November 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: November 17, 2009
• First Submitted That Met QC Criteria: November 17, 2009
• First Posted (Estimate): November 18, 2009

Study Record Updates

• Last Update Posted (Estimate): July 26, 2011
• Last Update Submitted That Met QC Criteria: July 25, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Thalassemia; BMT; HSCT
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: HORCSCT-0601