Trial record 1 of 279 for:    nichd AIDS/HIV
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: April 8, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Alendronate
Drug: Alendronate placebo
Dietary Supplement: Calcium carbonate/vitamin D
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Impact of Oral Alendronate Therapy on Bone Mineral Density in HIV-infected Children and Adolescents With Low Bone Mineral Density

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 51
Study Start Date: August 2009
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will receive alendronate tablet taken orally once weekly for 96 weeks
Drug: Alendronate
Oral tablet taken once weekly. Dosage is dependent on body weight
Dietary Supplement: Calcium carbonate/vitamin D
Tablet taken once or twice daily. Dosage is dependent on participant's measured vitamin D levels
Experimental: 2
Participants will receive alendronate tablet taken orally once weekly for 48 weeks before receiving alendronate placebo tablet for additional 48 weeks
Drug: Alendronate
Oral tablet taken once weekly. Dosage is dependent on body weight
Dietary Supplement: Calcium carbonate/vitamin D
Tablet taken once or twice daily. Dosage is dependent on participant's measured vitamin D levels
Placebo Comparator: 3
Participants will receive alendronate placebo tablet taken orally once weekly for 96 weeks
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

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 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.

  Eligibility

Ages Eligible for Study:   11 Years to 24 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00921557

Locations
United States, California
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
Los Angeles, California, United States, 90095-1752
United States, Florida
Pediatric Perinatal HIV Clinical Trials Unit CRS
Miami, Florida, United States, 33136
USF - Tampa NICHD CRS
Tampa, Florida, United States, 33606
United States, Illinois
Chicago Children's CRS
Chicago, Illinois, United States, 60614
United States, Maryland
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, United States, 01605
United States, Tennessee
St. Jude/UTHSC CRS
Memphis, Tennessee, United States, 38105
Brazil
SOM Federal University Minas Gerais Brazil NICHD CRS
Belo Horizonte, Minas Gerais, Brazil, 30130-100
Univ. of Sao Paulo Brazil NICHD CRS
Sao Paulo, Brazil, 14049-900
Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
Investigators
Study Chair: George K. Siberry, MD Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00921557     History of Changes
Other Study ID Numbers: P1076, 10669, IMPAACT P1076
Study First Received: June 12, 2009
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Bone mineral density

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Calcium Carbonate
Vitamin D
Ergocalciferols
Alendronate
Vitamins
Antacids
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Bone Density Conservation Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 17, 2014