Safety and Effectiveness of Alendronate for Bone Mineral Density in HIV-infected Children and Adolescents
- Conditions
- HIV Infection
- Interventions
- Registration Number
- NCT00921557
- Brief Summary
HIV-infected children, youth, and adults have lower bone mineral density (BMD) than would be expected for HIV-uninfected people of similar age, weight and race. As the majority of perinatally HIV-infected U.S. children are entering or in adolescence, the potential for HIV-related impaired BMD during the adolescent peak of bone mass acquisition is of particular concern. The primary purpose of this study was to compare changes from pre-treatment levels of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment with placebo in HIV-infected children and adolescents.
- Detailed Description
Puberty is a time when the foundation is laid for healthy bone mass. Over the course of puberty, 26% of bone mass is established in the 4-year period of peak height velocity and up to 60% of adult peak bone mass is established. Factors that affect normal bone mineralization include calcium intake, vitamin D status, degree of physical and weight bearing activities, hormones, genetics, body weight, and general health and nutrition status. HIV-infected children, youth, and adults have lower bone mineral density (BMD) than would be expected for healthy people of similar age, weight, and race. As the majority of perinatally HIV-infected U.S. children are entering or in adolescence, the potential for HIV-related impaired BMD during the adolescent peak of bone mass acquisition is of particular concern. The purpose of this study was to compare changes in BMD of the lumbar spine from pre-treatment levels to 24 and 48 weeks after alendronate treatment or placebo in HIV-infected children and adolescents.
Participants were randomized equally into one of three groups: Group 1A received alendronate for 96 weeks; Group 1B received alendronate for 48 weeks followed by placebo for 48 weeks; Group 2 received placebo for 48 weeks followed by alendronate for 48 weeks. All three groups were followed off treatment for an additional 48 weeks. Participants also received vitamin D/calcium for the duration of the study and were asked to perform 60 minutes of weight-bearing exercise each day.
Clinic visits were scheduled every 12 weeks after entry, with telephone contact visits one, four, and 28 weeks after entry and the week 48 visit. A physical exam and dental assessment was conducted at each clinic visit, and a history of adverse events collected. Dual Energy X-ray absorptiometry (DXA), hematology and chemistry panels were conducted at entry and weeks 24, 48, 72, 96 and 144. Lumbar spine and whole body (with head) BMD was measured using Hologic DXA scanners (QDR4500A, QDR4500W or Delphi A models).
The primary analysis compared changes from entry to 24 and 48 weeks in lumbar spine BMD between Groups 1A and 1B combined (both on alendronate for initial 48 weeks) vs. Group 2 (on placebo for 48 weeks). Study participants were unblinded after 96 weeks of follow-up (the primary completion date) but remained on study, off study treatment, for an additional 48 weeks.
Secondary laboratory outcomes listed in the protocol (bone marker turnover and Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio) and central fat content, which required application for additional funding for laboratory testing, will not be performed and no results will be available.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 2: Placebo/Alendronate Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks and calcium carbonate/vitamin D for 144 weeks 1B: Alendronate/Placebo Calcium carbonate/vitamin D Participants received alendronate for 48 weeks followed by placebo for 48 weeks and calcium carbonate/vitamin D for 144 weeks 2: Placebo/Alendronate Placebo Participants received placebo for 48 weeks followed by alendronate for 48 weeks and calcium carbonate/vitamin D for 144 weeks 1B: Alendronate/Placebo Alendronate Participants received alendronate for 48 weeks followed by placebo for 48 weeks and calcium carbonate/vitamin D for 144 weeks 2: Placebo/Alendronate Calcium carbonate/vitamin D Participants received placebo for 48 weeks followed by alendronate for 48 weeks and calcium carbonate/vitamin D for 144 weeks 1A: Alendronate/Alendronate Calcium carbonate/vitamin D Participants received alendronate for 96 weeks and calcium carbonate/vitamin D for 144 weeks 1B: Alendronate/Placebo Placebo Participants received alendronate for 48 weeks followed by placebo for 48 weeks and calcium carbonate/vitamin D for 144 weeks 1A: Alendronate/Alendronate Alendronate Participants received alendronate for 96 weeks and calcium carbonate/vitamin D for 144 weeks
- Primary Outcome Measures
Name Time Method Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD Weeks 0, 24 and 48 Percent change was calculated as (measurement at time T - measurement at baseline)/measurement at baseline \* 100%. Results for Groups 1A and 1B combined as both were on alendronate for the first 48 weeks.
Percentage of Participants Developing New Signs, Symptoms, Hematology or Chemistry Laboratory Values Greater Than or Equal to Grade 3 or New Cases of Jaw Osteonecrosis, Atrial Fibrillation, or Non-healing Fractures Week 0 to 48 Signs, symptoms, and laboratory values were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0 (December 2004). Results for Groups 1A and 1B were combined as both were on alendronate for the first 48 weeks.
- Secondary Outcome Measures
Name Time Method Change in CD4 Percent From Baseline Weeks 0, 48, 96 and 144 Change in percentage of lymphocytes that are CD4 cells calculated as measurement at each time point minus baseline measurement
Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD Weeks 0, 24 and 48 Percent change was calculated as (measurement at time T - measurement at baseline)/measurement at baseline \* 100%. Results for Groups 1A and 1B were combined as both were on alendronate for the first 48 weeks.
Effect of Other Known Bone Mineral Determinants (Age, Gender, Race/Ethnicity, Steroid Use, Depo-Provera, Tenofovir, Pubertal Stage, Bone Age, Vitamin D Status) and Inflammatory Cytokine Levels on Changes in Whole Body (With Head) BMD. Weeks 0, 24 and 48 A slope was fit for each participant to their percent change \[(measurement at time T - measurement at baseline)/measurement at baseline)\*100%\] in whole body (with head) BMD from baseline. Results represent average changes in whole body (with head) BMD over one year. Results are summarized for age, gender, ethnicity, tenofovir use, Tanner stage, bone age and vitamin D level. Only one participant was on steroids and none were using Dep-Provera. Inflammatory cytokine levels were not assayed. Results were combined for Groups 1A and 1B as both were on alendronate for the first 48 weeks.
Percent of Participants With HIV-1 RNA <= 400 Copies/ml Weeks 0, 48, 96 and 144 Percent calculated as number of participants with HIV-1 RNA \<= 400 copies/ml relative to the number of participants with HIV-1 RNA measured at that time point.
Percent Change From Baseline to Week 96 in Lumbar Spine BMD Weeks 0 and 96 Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline \* 100%. Includes Groups 1A and 1B only.
Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD Weeks 0 and 96 Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline \* 100%. Includes Groups 1A and 1B only.
Safety as Measured by the Incidence of New Signs, Symptoms, Hematology or Chemistry Laboratory Values Greater Than or Equal to Grade 3 or New Cases of Jaw Osteonecrosis, Atrial Fibrillation, or Non-healing Fractures Weeks 0 to 144 Signs, symptoms, and laboratory values were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0 (December 2004).
Effect of Other Known Bone Mineral Determinants (Age, Gender, Race/Ethnicity, Steroid Use, Depo-Provera, Tenofovir, Pubertal Stage, Bone Age, Vitamin D Status) and Inflammatory Cytokine Levels on Changes in Lumbar Spine BMD Weeks 0, 24 and 48 A slope was fit for each participant to their percent change \[(measurement at time T - measurement at baseline)/measurement at baseline)\*100%\] in lumbar spine BMD from baseline. Results represent average changes in lumbar spine BMD over one year. Results are summarized for age, gender, ethnicity, tenofovir use, Tanner stage, bone age and vitamin D level. Only one participant was on steroids and none were using Dep-Provera. Inflammatory cytokine levels were not assayed. Results were combined for Groups 1A and 1B as both were on alendronate for the first 48 weeks.
Change From Baseline to Week 48 in Bone Marker Turnover Weeks 0 and 48 Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Change From Baseline to Week 48 in Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio Weeks 0 and 48 Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Percent Change From Week 48 to Week 96 (Group 1B), Week 48 to Week 144 (Group 1B), and Week 96 to 144 (Group 2) in Lumbar Spine BMD Weeks 48, 96 and 144 Percent change was calculated as (measurement at time T2 - measurement at time T1)/measurement at Time T1 \* 100%.
Percent Change From Week 48 to Week 96 (Group 1B), Week 48 to Week 144 (Group 1B), and Week 96 to 144 (Group 2) in Whole Body (With Head) BMD Weeks 48, 96 and 144 Percent change was calculated as (measurement at time T2 - measurement at time T2)/measurement at time T1 \* 100%.
Correlation of Changes in Bone Marker Turnover With Changes in Lumbar Spine and Whole Body (With Head) BMD Weeks 0 and 48 Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Change in Centers for Disease Control (CDC) HIV Disease Category Weeks 144 Percentage of participants advancing in CDC HIV disease category from baseline throughout study follow-up
Correlation of Changes in RANKL/OPG Ratio With Changes in Lumbar Spine and Whole Body (With Head) BMD Weeks 0 and 48 Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Percent of Participants With Detectable Urinary Alendronate Weeks 48, 96 and 144 Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Change From Baseline to Week 48 in Central Fat Content Weeks 0 and 48 Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Correlation of Changes in Central Fat Content With Changes in Lumbar Spine and Whole Body (With Head) BMD Weeks 0 and 48 Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Trial Locations
- Locations (10)
Lurie Children's Hospital of Chicago (LCH) CRS
🇺🇸Chicago, Illinois, United States
Pediatric Perinatal HIV Clinical Trials Unit CRS
🇺🇸Miami, Florida, United States
WNE Maternal Pediatric Adolescent AIDS CRS
🇺🇸Worcester, Massachusetts, United States
David Geffen School of Medicine at UCLA NICHD CRS
🇺🇸Los Angeles, California, United States
Univ. of Sao Paulo Brazil NICHD CRS
🇧🇷Sao Paulo, Brazil
San Juan City Hosp. PR NICHD CRS
🇵🇷San Juan, Puerto Rico
SOM Federal University Minas Gerais Brazil NICHD CRS
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Johns Hopkins Univ. Baltimore NICHD CRS
🇺🇸Baltimore, Maryland, United States
USF - Tampa NICHD CRS
🇺🇸Tampa, Florida, United States
St. Jude Children's Research Hospital CRS
🇺🇸Memphis, Tennessee, United States