Bisphosphonate Therapy for HIV-Infected Adults With Decreased Bone Mineral Density

Bisphosphonate Therapy for HIV-Associated Osteopenia

Bisphosphonates are a type of drug used to prevent and treat bone loss. The purpose of this study is to determine if zoledronate, an investigational bisphosphonate, can improve bone mineral density (BMD) in HIV-infected adults.

Study hypothesis: Zoledronate will reduce bone resorption in HIV-infected persons with osteopenia.

Study Overview

• Status: Unknown
• Conditions: HIV Infections; Osteoporosis; Osteopenia
• Intervention / Treatment: Drug: Zoledronate; Drug: Zoledronate placebo

Detailed Description

Decreased BMD and bone loss is estimated to affect up to 67.5% of the HIV-infected population. HIV-associated bone loss may be a result of antiretroviral treatment (ART), but can also be caused by the infection itself. To date, treatment for this bone loss has not been established. Before prescribing drugs to treat bone loss, physicians must take into account patients' already demanding ART schedules and potential nonadherence. This study will evaluate the efficacy of a single IV dose of zoledronate, an investigational bisphosphonate, in treating HIV-associated bone loss.

This study will last 1 year. Participants will be randomly assigned to receive zoledronate or placebo at study entry; their assigned intervention will be given in a 20- to 30-minute infusion on an outpatient basis. There will be 7 study visits: at screening, study entry, Week 2, and Months 3, 6, 9, and 12. Blood collection will occur at all visits. Medical history, a physical exam, a dual-energy x-ray absorptiometry (DEXA) scan to measure bone density, and a nutrition evaluation will occur at selected visits.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-infected
• On stable antiretroviral regimen for at least 3 months
• Able to walk
• Lumbar spine or total hip BMD T-score at least 1.5 SD and no more than 3.5 SD below the mean BMD
• No prevalent fractures at entry OR 1 prevalent vertebral fracture that has been asymptomatic during the last 2 years prior to study entry
• HIV viral load of less than 5000 copies/ml within the 2 months prior to study entry
• CD4 count of more than 100 cells/mm3 within the 2 months prior to study entry
• Willing to use acceptable forms of contraception during the study period and for 6 months after study completion. Participants who are female and postmenopausal will be required to take hormone replacement therapy during this study.

Exclusion Criteria:

• Prior treatment with bisphosphonates or fluoride
• Use of supraphysiologic systemic estrogen/androgen therapy or corticosteroid therapy within the 3 months prior to study entry. Participants who have taken hormone replacement therapy are not excluded.
• Significant liver or kidney disease
• Hemoglobin less than 8 g/dL
• Serum calcium less than 8 mg/dL
• Laboratory evidence of low levels of estrogens or androgens
• Laboratory evidence of overactive parathyroid glands
• History of thyroid, parathyroid, or other endocrinologic disorder known to affect bone
• Current use of any therapy known to affect bone
• Current or history of cancer or chemotherapy
• Current or history of radiotherapy to the jaw
• Current osteomyelitis of the jaw or ongoing dental infection
• Recent tooth extraction or major dental procedure within 3 weeks of study entry
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Participants will receive zoledronate at study entry; their assigned intervention will be given in a 20- to 30-minute infusion on an outpatient basis	Drug: Zoledronate; Zoledronate infusion
Placebo Comparator: 2; Participants will receive zoledronate placebo at study entry; their assigned intervention will be given in a 20- to 30-minute infusion on an outpatient basis	Drug: Zoledronate placebo; Zoledronate placebo infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bone metabolic markers	Throughout study

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety outcomes	Throughout study

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Jeannie S. Huang, MD, MPH, University of California, San Diego

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Anticipated): October 1, 2007
• Study Completion (Anticipated): December 1, 2009

Study Registration Dates

• First Submitted: February 4, 2005
• First Submitted That Met QC Criteria: February 4, 2005
• First Posted (Estimate): February 7, 2005

Study Record Updates

• Last Update Posted (Estimate): September 26, 2008
• Last Update Submitted That Met QC Criteria: September 25, 2008
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Keywords: Treatment Experienced; Osteoporosis; Osteopenia; Bone Metabolism
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: 1R21AI058756-01 (U.S. NIH Grant/Contract)