Safety and Effectiveness of Alendronate for Bone Mineral Density in HIV-infected Children and Adolescents
Impact of Oral Alendronate Therapy on Bone Mineral Density in HIV-infected Children and Adolescents With Low Bone Mineral Density
3 other identifiers
interventional
52
3 countries
10
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2009
Longer than P75 for phase_2
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 12, 2009
CompletedFirst Posted
Study publicly available on registry
June 16, 2009
CompletedStudy Start
First participant enrolled
November 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2017
CompletedResults Posted
Study results publicly available
March 28, 2017
CompletedNovember 5, 2021
June 1, 2017
6.2 years
June 12, 2009
December 15, 2016
November 3, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD
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.
Weeks 0, 24 and 48
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
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.
Week 0 to 48
Secondary Outcomes (18)
Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD
Weeks 0, 24 and 48
Percent Change From Baseline to Week 96 in Lumbar Spine BMD
Weeks 0 and 96
Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD
Weeks 0 and 96
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
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
- +13 more secondary outcomes
Study Arms (3)
1A: Alendronate/Alendronate
EXPERIMENTALParticipants received alendronate for 96 weeks and calcium carbonate/vitamin D for 144 weeks
1B: Alendronate/Placebo
EXPERIMENTALParticipants received alendronate for 48 weeks followed by placebo for 48 weeks and calcium carbonate/vitamin D for 144 weeks
2: Placebo/Alendronate
EXPERIMENTALParticipants received placebo for 48 weeks followed by alendronate for 48 weeks and calcium carbonate/vitamin D for 144 weeks
Interventions
Oral tablet taken once weekly: 70 mg if participant greater than 30 kg or 35 mg if participant less than or equal to 30 kg
Tablet taken once or twice daily: calcium carbonate (600 mg) and vitamin D (400 IU) once daily for participants with 25-OH-vitamin D levels greater than or equal to 20 ng/mL or twice daily for those with 25-OH-vitamin D levels less than 20 ng/mL
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, 90095-1752, United States
Pediatric Perinatal HIV Clinical Trials Unit CRS
Miami, Florida, 33136, United States
USF - Tampa NICHD CRS
Tampa, Florida, 33606, United States
Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, 60614-3393, United States
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, 21287, United States
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, 01605, United States
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105, United States
SOM Federal University Minas Gerais Brazil NICHD CRS
Belo Horizonte, Minas Gerais, 30130-100, Brazil
Univ. of Sao Paulo Brazil NICHD CRS
São Paulo, 14049-900, Brazil
San Juan City Hosp. PR NICHD CRS
San Juan, 00936, Puerto Rico
Related Publications (5)
Clay PG, Voss LE, Williams C, Daume EC. Valid treatment options for osteoporosis and osteopenia in HIV-infected persons. Ann Pharmacother. 2008 May;42(5):670-9. doi: 10.1345/aph.1K465. Epub 2008 Apr 15.
PMID: 18413693BACKGROUNDMcComsey GA, Kendall MA, Tebas P, Swindells S, Hogg E, Alston-Smith B, Suckow C, Gopalakrishnan G, Benson C, Wohl DA. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS. 2007 Nov 30;21(18):2473-82. doi: 10.1097/QAD.0b013e3282ef961d.
PMID: 18025884BACKGROUNDStoch SA, Saag KG, Greenwald M, Sebba AI, Cohen S, Verbruggen N, Giezek H, West J, Schnitzer TJ. Once-weekly oral alendronate 70 mg in patients with glucocorticoid-induced bone loss: a 12-month randomized, placebo-controlled clinical trial. J Rheumatol. 2009 Aug;36(8):1705-14. doi: 10.3899/jrheum.081207. Epub 2009 Jun 1.
PMID: 19487264BACKGROUNDThe DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).
BACKGROUNDJacobson DL, Lindsey JC, Gordon C, Hazra R, Spiegel H, Ferreira F, Amaral FR, Pagano-Therrien J, Gaur A, George K, Benson J, Siberry GK. Alendronate Improves Bone Mineral Density in Children and Adolescents Perinatally Infected With Human Immunodeficiency Virus With Low Bone Mineral Density for Age. Clin Infect Dis. 2020 Aug 22;71(5):1281-1288. doi: 10.1093/cid/ciz957.
PMID: 31573608DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Melissa Allen, Director, IMPAACT Operations Center
- Organization
- Family Health International (FHI 360)
Study Officials
- STUDY CHAIR
George K. Siberry, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 12, 2009
First Posted
June 16, 2009
Study Start
November 1, 2009
Primary Completion
January 1, 2016
Study Completion
January 1, 2017
Last Updated
November 5, 2021
Results First Posted
March 28, 2017
Record last verified: 2017-06
Data Sharing
- IPD Sharing
- Will not share