Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Trial record 1 of 425 for:    (hiv OR aids) AND nichd
Previous Study | Return to List | Next Study

Safety and Effectiveness of Oral Alendronate Therapy on Bone Mineral Density in HIV-infected Children and Adolescents With Low Bone Mineral Density

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00921557
First received: June 12, 2009
Last updated: October 7, 2014
Last verified: October 2014

June 12, 2009
October 7, 2014
August 2009
February 2016   (final data collection date for primary outcome measure)
  • Pre-treatment levels of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment versus placebo, as measured by Hologic bone densitometers [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Safety of of alendronate use as measured by the incidence of new hematology or chemistry laboratory values greater than or equal to Grade 3; signs or symptoms; or new cases of jaw osteonecrosis, atrial fibrillation, or non-healing fractures [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Pre-treatment levels in BMD of the lumbar spine after 24 and 48 weeks of versus participants receiving placebo [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Safety of of alendronate use as measured by the incidence of new ≥ Grade 3 hematology or chemistry laboratory values, signs or symptoms, or new cases of jaw osteonecrosis, atrial fibrillation, or non-healing fractures [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00921557 on ClinicalTrials.gov Archive Site
  • Changes from pre-treatment levels of whole body BMD after alendronate treatment versus placebo [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Changes from pre-treatment levels of whole body and lumbar spine BMD alendronate treatment versus 48 weeks of alendronate followed by 48 weeks of placebo [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • 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 BMD after alendronate treatment [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Changes in BMD after completion of 48 weeks of alendronate therapy [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Alterations in pre-treatment bone marker turnover, receptor activator of nuclear factor kappa-B ligand/osteoprotegerin (RANKL/OPG) ratio, central fat content, and determination of whether the changes in these outcomes correlate with changes in BMD [ Time Frame: At study entry and Week 48 ] [ Designated as safety issue: No ]
  • Effect of alendronate therapy on changes in HIV status (as measured by changes in viral load, CD4% and CDC disease category) and determination whether the changes in these outcomes correlate with changes in BMD [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Duration of detectable urinary alendronate in adolescent participants who have completed 48 and 96 weeks of alendronate therapy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Changes from pre-treatment levels in whole body BMD after alendronate treatment versus placebo [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Changes from pre-treatment levels in whole body and lumbar spine BMD alendronate treatment versus 48 weeks of alendronate followed by 48 weeks of placebo [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Safety of alendronate use as measured by the incidence of new ≥ Grade 3 hematology or chemistry laboratory values, signs or symptoms, or new cases of jaw osteonecrosis, atrial fibrillation, or non-healing fractures [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • 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 BMD after alendronate treatment [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Changes in BMD after completion of 48 weeks of alendronate therapy [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Alterations in pre-treatment bone marker turnover, RANKL/OPG ratio, central fat content (by whole body DXA) after 48 weeks of alendronate therapy and determine if the changes in these outcomes correlate with changes in BMD [ Time Frame: At study entry and Week 48 ] [ Designated as safety issue: No ]
  • Effect of alendronate therapy on changes in HIV status (as measured by changes in viral load, CD4% and CDC disease category) and determine if the changes in these outcomes correlate with changes in BMD [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Duration of detectable urinary alendronate in adolescent participants who have completed 48 and 96 weeks of alendronate therapy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety and Effectiveness of Oral Alendronate Therapy on Bone Mineral Density in HIV-infected Children and Adolescents With Low Bone Mineral Density
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 is 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.

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 is to compare changes from pretreatment levels of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment with placebo in HIV-infected children and adolescents.

This study will last approximately 144 weeks. Participants will be randomized into one of three groups.

Participants in Group 1 will receive alendronate for 96 weeks. Participants in Group 2 will receive alendronate for 48 weeks and alendronate placebo for an additional 48 weeks. Participants in Group 3 will receive placebo for 48 weeks followed by alendronate for 48 weeks. All three groups will be followed off treatment for an additional 48 weeks. All participants will receive vitamin D/calcium for the duration of the study.

There will be 13 study visits for each participant. They will occur at study entry and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144. A physical exam, targeted events history, and adherence questionnaire will occur at all visits. Blood and urine collection, Tanner stage assessment, DXA scan, and radiograph will occur at most visits. Participants will also complete a questionnaire about smoking behavior at screening. Participants will be contacted by telephone 7 times throughout the study at Weeks 1, 4, 28, 49, 52, 76, and 100 to screen for adverse events, assess adherence, and reinforce study instructions.

Information provided by adolescent participants about sexual activity, pregnancy, and smoking and alcohol use will not be shared without the participants' permission.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
HIV Infections
  • Drug: Alendronate
    Oral tablet taken once weekly. Dosage is dependent on body weight
  • Drug: Alendronate placebo
    Oral tablet taken once weekly
  • Dietary Supplement: Calcium carbonate/vitamin D
    Tablet taken once or twice daily. Dosage is dependent on participant's measured vitamin D levels
  • Experimental: 1
    Participants will receive alendronate tablet taken orally once weekly for 96 weeks
    Interventions:
    • Drug: Alendronate
    • Dietary Supplement: Calcium carbonate/vitamin D
  • Experimental: 2
    Participants will receive alendronate tablet taken orally once weekly for 48 weeks before receiving alendronate placebo tablet for additional 48 weeks
    Interventions:
    • Drug: Alendronate
    • Dietary Supplement: Calcium carbonate/vitamin D
  • Placebo Comparator: 3
    Participants will receive alendronate placebo tablet taken orally once weekly for 96 weeks
    Interventions:
    • Drug: Alendronate placebo
    • Dietary Supplement: Calcium carbonate/vitamin D

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
51
Not Provided
February 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Documentation of HIV-1 infection is defined as positive results from two samples collected at different time points. All samples tested must be whole blood, serum, or plasma. For studies conducted under an IND, all test methods should be FDA-approved if available. If FDA-approved methods are not available, test methods should be verified according to GCLP and approved by the IMPAACT central laboratory. Results documented in the clinical record from past testing may be used to satisfy the criteria for documentation of HIV-1 infection. More information on this criterion can be found in the protocol.
  • HIV-infected. Infection must have been acquired prior to puberty.
  • For participants receiving antiretroviral therapy, antiretroviral agents must be steady for at least 12 weeks prior to study entry and have a viral load less than 10,000 copies/mL
  • Lumbar spine DXA BMD z-score lower than -1.5 OR history of fragility fracture within the prior 12 months (regardless of DXA result). More information about this criterion can be found in the protocol.
  • Available for routine dental exam and care every 6 months
  • Demonstrates ability and willingness to swallow study medications
  • For females, participants must agree to use at least two forms of accepted contraceptives. More information about this criterion can be found in the protocol.

Exclusion Criteria:

  • Body weight of more than 300 lbs.
  • For female participants, received Depo-Provera for less than 1 full year during the year prior to study entry. More information about this criterion can be found in the protocol.
  • 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 that is expected to require more than basic restorative care
  • Esophageal or gastric ulcer, chronic nonsteroidal anti-inflammatory drug (NSAID) use, aspirin use
  • Tenofovir disoproxil fumarate (TDF) taken by participants for less than 24 weeks during the 24 weeks prior to study entry. More information about this criterion can be found in the protocol.
  • 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 is performed)
  • Known abnormalities of the esophagus that delay esophageal emptying such as stricture or achalasia
  • 25-OH vitamin D less than 10 ng/mL
  • Pregnant or breastfeeding
Both
11 Years to 24 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Brazil,   Puerto Rico
 
NCT00921557
P1076, 10669, IMPAACT P1076
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Chair: George K. Siberry, MD Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP