HIV InfectionPhase 2NCT00921557
Safety and Effectiveness of Alendronate for Bone Mineral Density in HIV-infected Children and Adolescents
A Phase 2 study testing Alendronate and Calcium carbonate/vitamin D in people with HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 11 to 24 years
- Conditions the study is for
- HIV Infection
- What is being tested?
- Alendronate and Calcium carbonate/vitamin D
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 10 sitesin 3 countries
- Study dates
- Nov 2009to Jan 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 11 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United States7 sites
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, 21287
Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, 60614-3393
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, 90095-1752
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105
Pediatric Perinatal HIV Clinical Trials Unit CRS
Miami, Florida, 33136
USF - Tampa NICHD CRS
Tampa, Florida, 33606
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, 01605
Brazil2 sites
SOM Federal University Minas Gerais Brazil NICHD CRS
Belo Horizonte, Minas Gerais, 30130-100
Univ. of Sao Paulo Brazil NICHD CRS
São Paulo, 14049-900
About this study
Official title: Impact of Oral Alendronate Therapy on Bone Mineral Density in HIV-infected Children and Adolescents With Low Bone Mineral Density
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.
Read the 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.
- Conditions
- HIV Infection
- Being tested
- Alendronate, Placebo, Calcium carbonate/vitamin D
- Keywords
- Bone mineral density
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlendronateDrug
Also called Fosamax
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
PlaceboDrug
Oral tablet taken once weekly
Calcium carbonate/vitamin DDietary supplement
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
| Study group | Role | What they receive |
|---|---|---|
| 1A: Alendronate/Alendronate | Experimental | Participants received alendronate for 96 weeks and calcium carbonate/vitamin D for 144 weeks Receives: Drug: Alendronate; Dietary Supplement: Calcium carbonate/vitamin D |
| 1B: Alendronate/Placebo | Experimental | Participants received alendronate for 48 weeks followed by placebo for 48 weeks and calcium carbonate/vitamin D for 144 weeks Receives: Drug: Alendronate; Drug: Placebo; Dietary Supplement: Calcium carbonate/vitamin D |
| 2: Placebo/Alendronate | Experimental | Participants received placebo for 48 weeks followed by alendronate for 48 weeks and calcium carbonate/vitamin D for 144 weeks Receives: Drug: Alendronate; Drug: Placebo; Dietary Supplement: Calcium carbonate/vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Week 0 to 48
Secondary outcomes (18)
Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD
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.
Measured: Weeks 0, 24 and 48
Percent Change From Baseline to Week 96 in Lumbar Spine BMD
Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline * 100%. Includes Groups 1A and 1B only.
Measured: Weeks 0 and 96
Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD
Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline * 100%. Includes Groups 1A and 1B only.
Measured: 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
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).
Measured: 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
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.
Measured: 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.
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.
Measured: 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
Percent change was calculated as (measurement at time T2 - measurement at time T1)/measurement at Time T1 * 100%.
Measured: 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
Percent change was calculated as (measurement at time T2 - measurement at time T2)/measurement at time T1 * 100%.
Measured: Weeks 48, 96 and 144
Change From Baseline to Week 48 in Bone Marker Turnover
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Measured: Weeks 0 and 48
Correlation of Changes in Bone Marker Turnover With Changes in Lumbar Spine and Whole Body (With Head) BMD
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Measured: Weeks 0 and 48
Change From Baseline to Week 48 in Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Measured: Weeks 0 and 48
Correlation of Changes in RANKL/OPG Ratio With Changes in Lumbar Spine and Whole Body (With Head) BMD
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Measured: Weeks 0 and 48
Change From Baseline to Week 48 in Central Fat Content
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Measured: Weeks 0 and 48
Correlation of Changes in Central Fat Content With Changes in Lumbar Spine and Whole Body (With Head) BMD
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Measured: Weeks 0 and 48
Percent of Participants With HIV-1 RNA <= 400 Copies/ml
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.
Measured: Weeks 0, 48, 96 and 144
Change in CD4 Percent From Baseline
Change in percentage of lymphocytes that are CD4 cells calculated as measurement at each time point minus baseline measurement
Measured: Weeks 0, 48, 96 and 144
Change in Centers for Disease Control (CDC) HIV Disease Category
Percentage of participants advancing in CDC HIV disease category from baseline throughout study follow-up
Measured: Weeks 144
Percent of Participants With Detectable Urinary Alendronate
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Measured: Weeks 48, 96 and 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2009 (estimated)
- Study startNov 2009
- Primary completionJan 2016
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- George K. Siberry, MD, Study chair, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00921557
- Sponsor's protocol ID
- P1076
- Other IDs
- 10669, IMPAACT P1076
- Status last verified
- Jun 2017
- First submitted
- 12 Jun 2009
- Last updated
- 5 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 18413693McComsey 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.
PubMed 18025884Stoch 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.
PubMed 19487264The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).
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.
PubMed 31573608
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Oral Alendronate Therapy on Bone Mineral Density in HIV-infected Children and Adolescents With Low Bone Mineral Density
- ClinicalTrials.gov ID
- NCT00921557
- Acronym / sponsor ID
- P1076
- Conditions
- HIV Infection
- Keywords
- Bone mineral density
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Nov 2009 (actual)
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 16 Jun 2009 (estimated)
- Results
- Posted 28 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1A: Alendronate/Alendronate | Experimental | Drug: Alendronate, Dietary Supplement: Calcium carbonate/vitamin DParticipants received alendronate for 96 weeks and calcium carbonate/vitamin D for 144 weeks |
| 1B: Alendronate/Placebo | Experimental | Drug: Alendronate, Drug: Placebo, Dietary Supplement: Calcium carbonate/vitamin DParticipants received alendronate for 48 weeks followed by placebo for 48 weeks and calcium carbonate/vitamin D for 144 weeks |
| 2: Placebo/Alendronate | Experimental | Drug: Alendronate, Drug: Placebo, Dietary Supplement: Calcium carbonate/vitamin DParticipants received placebo for 48 weeks followed by alendronate for 48 weeks and calcium carbonate/vitamin D for 144 weeks |
Who may qualify
- Ages
- 11 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlendronateAlso: FosamaxOral tablet taken once weekly: 70 mg if participant greater than 30 kg or 35 mg if participant less than or equal to 30 kg | Drug | 1A: Alendronate/Alendronate, 1B: Alendronate/Placebo, 2: Placebo/Alendronate |
| PlaceboOral tablet taken once weekly | Drug | 1B: Alendronate/Placebo, 2: Placebo/Alendronate |
| Calcium carbonate/vitamin DTablet 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 | Dietary supplement | 1A: Alendronate/Alendronate, 1B: Alendronate/Placebo, 2: Placebo/Alendronate |
Primary outcome
Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD
Time frame: 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
Time frame: 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.
18 secondary outcomes
Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD
Time frame: Weeks 0, 24 and 48
Percent Change From Baseline to Week 96 in Lumbar Spine BMD
Time frame: Weeks 0 and 96
Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: Weeks 48, 96 and 144
Change From Baseline to Week 48 in Bone Marker Turnover
Time frame: Weeks 0 and 48
Correlation of Changes in Bone Marker Turnover With Changes in Lumbar Spine and Whole Body (With Head) BMD
Time frame: Weeks 0 and 48
Change From Baseline to Week 48 in Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio
Time frame: Weeks 0 and 48
Correlation of Changes in RANKL/OPG Ratio With Changes in Lumbar Spine and Whole Body (With Head) BMD
Time frame: Weeks 0 and 48
Change From Baseline to Week 48 in Central Fat Content
Time frame: Weeks 0 and 48
Correlation of Changes in Central Fat Content With Changes in Lumbar Spine and Whole Body (With Head) BMD
Time frame: Weeks 0 and 48
Percent of Participants With HIV-1 RNA <= 400 Copies/ml
Time frame: Weeks 0, 48, 96 and 144
Change in CD4 Percent From Baseline
Time frame: Weeks 0, 48, 96 and 144
Change in Centers for Disease Control (CDC) HIV Disease Category
Time frame: Weeks 144
Percent of Participants With Detectable Urinary Alendronate
Time frame: Weeks 48, 96 and 144
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18413693Clay 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.
- Background: PubMed 18025884McComsey 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.
- Background: PubMed 19487264Stoch 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.
- BackgroundThe DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).
- Derived from this study: PubMed 31573608Jacobson 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George K. Siberry, MD study chair
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alendronate and Calcium carbonate/vitamin D in people with HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Brazil, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD (time frame: Weeks 0, 24 and 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00921557, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.