NCT01228318

Bone Loss and Immune Reconstitution in HIV/AIDS (BLIR-HIV)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 63 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 30 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

With the increasing age of people living with HIV/AIDS, age-induced osteoporosis is likely to be compounded by HIV/AIDS and HAART-associated bone loss. Mechanistically, osteoclasts the cells responsible for bone resorption form under the influence of the key osteoclastogenic cytokine receptor activator of nuclear factor kappa-Β ligand (RANKL). The osteoclastogenic and proresorptive activities of RANKL are moderated by its physiological decoy receptor osteoprotegerin (OPG). Imbalance in the ratio of RANKL to OPG alters osteoclastic bone resorption and lead to osteoporosis. Activated T- and B-cells are a major source of RANKL, while normal physiological B-cells are a major source of OPG. T-cells regulate the production of OPG by B-cells. Thus changes in the immune system induced by HIV/AIDS and/or by HAART could affect B-cell and T-cells RANKL and OPG production. Indeed, data from our group shows that in an animal model of HIV/AIDS, the HIV-1 Transgenic rat, the development of osteoporosis is recapitulated as observed in HIV-infected patients, and B-cell OPG and RANKL production are concurrently down regulated and upregulated respectively. Furthermore, preliminary data in HIV-infected subjects suggests dramatic acute upswing in bone resorption following HAART initiation that peaks at 12 weeks and then declines. Based on these findings, the investigators hypothesize HAART associated bone loss is driven by immune reconstitution. Because this effect of HAART is dramatic in magnitude but short in duration, the investigators propose to apply antiresorptive agent (zoledronic acid, reclast®) to specifically spare patients from this dramatic but acute bone damage.

Detailed description

In a prospective, blinded placebo-controlled randomized trial, treatment naïve HIV-infected subjects initiating HAART will be assigned to HAART + zoledronic acid or HAART + placebo. Serial assessment of serum levels of bone markers, cellular expression of OPG/RANKL and other cytokines, cellular immune activation markers, serum bone regulating hormones, and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) scan will be undertaken at pre-defined time points from baseline through week 144 of HAART. In the primary analysis, changes in serum C-Terminal Telopeptide (CTx) level, BMD, and cellular OPG/RANKL expression from baseline through week 24 will be quantitated and subsequently compared between treatment arms. In addition, the impact of zoledronic acid administration on these covariates will be assessed at various study time points. The relationship between OPG/RANKL expression, immune activation, serum bone regulating hormonal levels, and bone turnover will be evaluated.

Conditions

• HIV Infection
• Bone Loss
• Osteopenia
• Osteoporosis

Interventions

Type	Name	Description
DRUG	Zoledronic acid	1. A single dose of reclast containing 5 mg/100 mL ready-to-infuse zoledronic acid solution administered over 15-30 minutes. 2. A single dose of placebo containing 220 mg mannitol and 24 mg sodium citrate in a 100 mL ready-to-infuse solution, administered over 15-30 minutes.

Timeline

• Start date: 2011-01-01
• Primary completion: 2017-04-13
• Completion: 2017-04-13
• First posted: 2010-10-26
• Last updated: 2018-06-26
• Results posted: 2018-06-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study