Safety and Effectiveness of Alendronate for Bone Mineral Density in HIV-infected Children and Adolescents
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: Alendronate; Placebo; Calcium carbonate/vitamin D
Intervention description: 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; Oral tablet taken once weekly; 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
Intervention MeSH terms: Vitamin D; Alendronate; Calcium Carbonate; Calcium
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 52.0
Sex: All
Minimum age: 11 Years
Maximum age: 24 Years
Healthy volunteers: No
Keywords: Bone mineral density

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.
    

Eligibility criteria:

        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