- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT00921557
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
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
-
-
-
Sao Paulo, Brazílie, 14049-900
- Univ. of Sao Paulo Brazil NICHD CRS
-
-
Minas Gerais
-
Belo Horizonte, Minas Gerais, Brazílie, 30130-100
- SOM Federal University Minas Gerais Brazil NICHD CRS
-
-
-
-
-
San Juan, Portoriko, 00936
- San Juan City Hosp. PR NICHD CRS
-
-
-
-
California
-
Los Angeles, California, Spojené státy, 90095-1752
- David Geffen School of Medicine at UCLA NICHD CRS
-
-
Florida
-
Miami, Florida, Spojené státy, 33136
- Pediatric Perinatal HIV Clinical Trials Unit CRS
-
Tampa, Florida, Spojené státy, 33606
- USF - Tampa NICHD CRS
-
-
Illinois
-
Chicago, Illinois, Spojené státy, 60614-3393
- Lurie Children's Hospital of Chicago (LCH) CRS
-
-
Maryland
-
Baltimore, Maryland, Spojené státy, 21287
- Johns Hopkins Univ. Baltimore NICHD CRS
-
-
Massachusetts
-
Worcester, Massachusetts, Spojené státy, 01605
- WNE Maternal Pediatric Adolescent AIDS CRS
-
-
Tennessee
-
Memphis, Tennessee, Spojené státy, 38105
- St. Jude Children's Research Hospital CRS
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
---|---|
Experimentální: 1A: Alendronate/Alendronate
Participants received alendronate for 96 weeks and calcium carbonate/vitamin D for 144 weeks
|
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
Ostatní jména:
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
|
Experimentální: 1B: Alendronate/Placebo
Participants received alendronate for 48 weeks followed by placebo for 48 weeks and calcium carbonate/vitamin D for 144 weeks
|
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
Ostatní jména:
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
Oral tablet taken once weekly
|
Experimentální: 2: Placebo/Alendronate
Participants received placebo for 48 weeks followed by alendronate for 48 weeks and calcium carbonate/vitamin D for 144 weeks
|
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
Ostatní jména:
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
Oral tablet taken once weekly
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD
Časové okno: 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.
|
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
Časové okno: 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.
|
Week 0 to 48
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD
Časové okno: 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.
|
Weeks 0, 24 and 48
|
Percent Change From Baseline to Week 96 in Lumbar Spine BMD
Časové okno: 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.
|
Weeks 0 and 96
|
Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD
Časové okno: 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.
|
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
Časové okno: 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).
|
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
Časové okno: 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.
|
Weeks 0, 24 and 48
|
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.
Časové okno: 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.
|
Weeks 0, 24 and 48
|
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
Časové okno: Weeks 48, 96 and 144
|
Percent change was calculated as (measurement at time T2 - measurement at time T1)/measurement at Time T1 * 100%.
|
Weeks 48, 96 and 144
|
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
Časové okno: Weeks 48, 96 and 144
|
Percent change was calculated as (measurement at time T2 - measurement at time T2)/measurement at time T1 * 100%.
|
Weeks 48, 96 and 144
|
Change From Baseline to Week 48 in Bone Marker Turnover
Časové okno: Weeks 0 and 48
|
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
|
Weeks 0 and 48
|
Correlation of Changes in Bone Marker Turnover With Changes in Lumbar Spine and Whole Body (With Head) BMD
Časové okno: Weeks 0 and 48
|
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
|
Weeks 0 and 48
|
Change From Baseline to Week 48 in Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio
Časové okno: Weeks 0 and 48
|
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
|
Weeks 0 and 48
|
Correlation of Changes in RANKL/OPG Ratio With Changes in Lumbar Spine and Whole Body (With Head) BMD
Časové okno: Weeks 0 and 48
|
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
|
Weeks 0 and 48
|
Change From Baseline to Week 48 in Central Fat Content
Časové okno: Weeks 0 and 48
|
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
|
Weeks 0 and 48
|
Correlation of Changes in Central Fat Content With Changes in Lumbar Spine and Whole Body (With Head) BMD
Časové okno: Weeks 0 and 48
|
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
|
Weeks 0 and 48
|
Percent of Participants With HIV-1 RNA <= 400 Copies/ml
Časové okno: 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.
|
Weeks 0, 48, 96 and 144
|
Change in CD4 Percent From Baseline
Časové okno: 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
|
Weeks 0, 48, 96 and 144
|
Change in Centers for Disease Control (CDC) HIV Disease Category
Časové okno: Weeks 144
|
Percentage of participants advancing in CDC HIV disease category from baseline throughout study follow-up
|
Weeks 144
|
Percent of Participants With Detectable Urinary Alendronate
Časové okno: Weeks 48, 96 and 144
|
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
|
Weeks 48, 96 and 144
|
Spolupracovníci a vyšetřovatelé
Spolupracovníci
Vyšetřovatelé
- Studijní židle: George K. Siberry, MD, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Publikace a užitečné odkazy
Obecné publikace
- The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).
- McComsey 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.
- 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.
- Stoch 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.
- Jacobson 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- RNA virové infekce
- Virová onemocnění
- Infekce
- Infekce přenášené krví
- Přenosné nemoci
- Pohlavně přenosné choroby, virové
- Pohlavně přenosné nemoci
- Lentivirové infekce
- Retroviridae infekce
- Syndromy imunologické nedostatečnosti
- Onemocnění imunitního systému
- HIV infekce
- Fyziologické účinky léků
- Molekulární mechanismy farmakologického působení
- Gastrointestinální látky
- Mikroživiny
- Vitamíny
- Činidla pro zachování hustoty kostí
- Hormony a látky regulující vápník
- Antacida
- Vitamín D
- Vápník
- Alendronát
- Uhličitan vápenatý
Další identifikační čísla studie
- P1076
- 10669 (Jiný identifikátor: Fred Hutch/University of Washington Cancer Consortium)
- IMPAACT P1076
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
Klinické studie na HIV infekce
-
Helsinki University Central HospitalUniversity of Turku; Oulu University Hospital; Kuopio University Hospital; Tampere...NáborHysterektomie | Antibiotika | Infection Post Op | ProfylaktickýFinsko
-
University of MalayaTeleflexNáborCLABSI - Central Line Associated Bloodstream InfectionMalajsie
-
Sinocelltech Ltd.NáborHPV Infection Vaccine Safety SCT1000Čína
-
Duke UniversityDokončenoCentral Line-associated Bloodstream Infection (CLABSI)Spojené státy
-
Catholic University of the Sacred HeartDokončenoCentral Line-associated Bloodstream Infection (CLABSI)
-
Johns Hopkins UniversityDokončenoCLABSI - Central Line Associated Bloodstream InfectionSpojené státy
-
Burdenko Neurosurgery InstituteDokončenoHyperglykémie | Kraniotomie | Infection Post OpItálie, Ruská Federace
-
National Taiwan University HospitalDokončenoCentral Line-associated Bloodstream Infection (CLABSI)Tchaj-wan
-
National Taiwan University Hospital Hsin-Chu BranchDokončenoCentral Line-associated Bloodstream Infection (CLABSI)
-
Princess Maxima Center for Pediatric OncologyUMC Utrecht; Dutch Cancer SocietyNáborCentral Line-associated Bloodstream Infection (CLABSI)Holandsko