Phase 2
N=52
Safety and Effectiveness of Alendronate for Bone Mineral Density in HIV-infected Children and Adolescents
HIV Infection
Bottom Line
View on ClinicalTrials.gov: NCT00921557 ↗Enrolled (actual)
52
Serious AEs
14.0%
Results posted
Mar 2017
Primary outcome: Primary: Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD — 14.4; 5.5; 15.9; 7.1 Percent change from baseline — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Alendronate (Drug); Placebo (Drug); Calcium carbonate/vitamin D (Dietary_supplement)
- Age
- Pediatric, Adult · 11+ yrs
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Jan 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD |
14.4; 5.5; 15.9; 7.1 | <0.001 sig |
| PRIMARY 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 |
5; 2 | >0.99 |
| SECONDARY Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD |
5.5; 0.3; 10.7; 5.2 | — |
| SECONDARY Percent Change From Baseline to Week 96 in Lumbar Spine BMD |
24.9; 14.8 | — |
| SECONDARY Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD |
19.6; 10.3 | — |
| SECONDARY 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 |
2; 3; 2; 1; 3; 2 | — |
| SECONDARY 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 |
20.3; 6.8; 25.4; 9.4; 19.4; 4.8 | — |
| SECONDARY 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. |
11.4; 4.1; 14.0; 8.2; 9.8; 0.3 | — |
| SECONDARY 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 |
0.9; 2.0; 1.7 | — |
| SECONDARY 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 |
0.8; 0.5; 0.9 | — |
| SECONDARY Change From Baseline to Week 48 in Bone Marker Turnover |
— | — |
| SECONDARY Correlation of Changes in Bone Marker Turnover With Changes in Lumbar Spine and Whole Body (With Head) BMD |
— | — |
| SECONDARY Change From Baseline to Week 48 in Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio |
— | — |
| SECONDARY Correlation of Changes in RANKL/OPG Ratio With Changes in Lumbar Spine and Whole Body (With Head) BMD |
— | — |
| SECONDARY Change From Baseline to Week 48 in Central Fat Content |
— | — |
| SECONDARY Correlation of Changes in Central Fat Content With Changes in Lumbar Spine and Whole Body (With Head) BMD |
— | — |
| SECONDARY Percent of Participants With HIV-1 RNA <= 400 Copies/ml |
10; 16; 15; 10; 16; 14 | — |
| SECONDARY Change in CD4 Percent From Baseline |
0; 1; 1; 0; -1; 2 | — |
| SECONDARY Change in Centers for Disease Control (CDC) HIV Disease Category |
1; 0; 0; 0; 1; 0 | — |
| SECONDARY Percent of Participants With Detectable Urinary Alendronate |
— | — |
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.
Eligibility Criteria
Inclusion Criteria (Version 2.0 of protocol):
- Documentation of HIV-1 infection
- HIV-infection acquired before puberty
- For participants receiving antiretroviral therapy, must have been on the same antiretroviral agents for at least 12 weeks prior to study entry and have a viral load less than 10,000 copies/mL. For participants not receiving antiretroviral therapy, must have not been on antiretroviral agents for at least 12 weeks prior to study entry and have no indication for therapy
- Lumbar spine DXA BMD z-score less than -1.5 or history of fragility fracture within the prior 12 months (regardless of DXA result).
- Available for routine dental exam and care every 6 months
- Demonstrated ability and willingness to swallow study medications
- Females of reproductive potential must have had a negative pregnancy test at screening and within 48 hours prior to study entry. They must also have agreed to avoid pregnancy while on the study and if engaging in sexual activity, use at least two forms of contraception.
- Parent or legal guardian able and willing to provide signed informed consent for children who could not provide consent for themselves.
Exclusion Criteria (Version 2.0 of protocol):
- Body weight more than 300 lbs.
- For female participants: if on Depo-Provera, they must have been on it for at least 1 year prior to study entry; if not on Depa-Provera, they must have not been on it for at least 1 year prior to study entry.
- Anticonvulsant therapy
- Proven growth hormone deficiency
- Use of growth hormone in the 12 months prior to entry
- Primary hyperparathyroidism
- Hypoparathyroidism
- Renal failure
- Cushing syndrome
- Active dental infection
- Dental or periodontal disease expected to require more than basic restorative care
- Pregnancy or lactation
- Esophageal or gastric ulcer, chronic nonsteroidal anti-inflammatory drug (NSAID) use, or aspirin use
- Tenofovir disoproxil fumarate (TDF): if on TDF, they must have been on it for at least 6 months prior to study entry; if not on TDF, they must have not been on it for at least 6 months prior to study entry.
- Hemoglobin less than 10 g/dL
- Any past pharmacologic treatment (except vitamin D and/or calcium supplementation) for low bone density
- Inability to stand or sit upright for at least 30 minutes
- Hypersensitivity to any component of alendronate
- Hypocalcemia (less than the lower limit of normal established by the local laboratory in which it was performed)
- Known abnormalities of the esophagus that delay esophageal emptying such as stricture or achalasia
- 25-OH vitamin D less than 10 ng/mL in combination with elevated intact PTH above the upper limit of normal for the local laboratory in which it was performed
Data sourced from ClinicalTrials.gov (NCT00921557). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.