Bone Loss and Immune Reconstitution in HIV/AIDS (BLIR-HIV) (BLIR-HIV)
|ClinicalTrials.gov Identifier: NCT01228318|
Recruitment Status : Completed
First Posted : October 26, 2010
Results First Posted : June 25, 2018
Last Update Posted : June 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|HIV Infection Bone Loss Osteopenia Osteoporosis||Drug: Zoledronic acid||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||63 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Bone Loss and Immune Reconstitution in HIV/AIDS (BLIR-HIV)|
|Study Start Date :||January 2011|
|Actual Primary Completion Date :||April 13, 2017|
|Actual Study Completion Date :||April 13, 2017|
Experimental: Zoledronic acid
Subjects in this arm will receive 5 milligram (mg) per 100 milliliter (mL) solution of zoledronic acid infused intravenously over 15-30 minutes under the supervision of study personnel.
Drug: Zoledronic acid
Other Name: Reclast
Placebo Comparator: Placebo
Subjects in the placebo arm will receive placebo containing 220 mg mannitol and 24 mg sodium citrate in a 100 mL ready-to-infuse solution administered iv over 15-30 minutes under the supervision of study personnel.
Drug: Zoledronic acid
Other Name: Reclast
- Baseline-Adjusted Means for C-terminal Telopeptide of Collagen (CTx) Levels [ Time Frame: Baseline, Week 12 through Week 144 ]Serum C-terminal telopeptide of collagen (CTx) levels through week 144 were examined by evaluating the baseline-adjusted means. The baseline-adjusted CTx mean is defined as the predicted response value obtained by fitting the regression equation for each treatment arm at the mean baseline value for the 2 treatment arms. The adjusted means were estimated using analysis of covariance at each scheduled clinical visit. The expected outcome is that HIV-infected individuals will display increased indices of bone resorption (CTx) as a result of diminished bone mineral density (BMD). Lower CTx values indicate that better maintenance of bone mineral density.
- Baseline-Adjusted Means of Osteocalcin [ Time Frame: Baseline, Week 144 ]Osteocalcin was evaluated to examine the inhibitory effect of single dose zoledronic acid on HAART associated changes in markers of bone turnover. Osteocalcin is released from bone during resorption and higher levels in the circulatory system indicate increased bone turnover. HIV-infected individuals are expected to have increased bone resorption. The baseline-adjusted osteocalcin mean is defined as the predicted response value obtained by fitting the regression equation for each treatment arm at the mean baseline value for the 2 treatment arms. The adjusted means were estimated using analysis of covariance at the Week 144 clinic visit. Baseline-adjusted means of osteocalcin at week 144 are presented.
- Baseline-Adjusted Means of Dual-energy X-ray Absorptiometry (DXA) [ Time Frame: Baseline, Week 144 ]Development of osteoporosis was assessed by examining bone mineral density (BMD) by DXA scan. Baseline-adjusted means of DXA scan Z-scores are presented for the lumbar spine (L1-L4), left hip, and femur neck. The baseline-adjusted BMD mean is defined as the predicted response value obtained by fitting the regression equation for each treatment arm at the mean baseline value for the 2 treatment arms. The adjusted means were estimated using analysis of covariance at the Week 144 clinic visit. Bone density Z-scores tell how close to the average that a person is (adjusted for age, race, and gender). A Z-score of 0 means the value matches that of the average person. Z-score values below 0 indicate lower than average bone density while values above 0 indicate higher bone density than the average person.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01228318
|United States, Georgia|
|Grady Infectious Diseases Clinic (Ponce Center)|
|Atlanta, Georgia, United States, 30308|
|Principal Investigator:||Igho Ofotokun, MD, MSc||Emory University|
|Principal Investigator:||Mervyn N Weitzmann, PhD||Emory University|