Effect of Tenofovir DF on Bone Metabolism in Children

NCT00088309 | Completed Phase 2

• 2 other identifiers: 04023404-C-0234
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the long-term effects, particularly on bone metabolism, of the drug tenofovir DF in children with HIV infection. Tenofovir DF is approved for treating HIV-infected adults, but its use in children has not yet been approved. The drug may be helpful for children who have been treated with many other drugs and still have detectable HIV in their blood despite ongoing therapy. In a previous study, many children given tenofovir DF responded well, with increases in T-cell counts and decreases in viral load. However, many children also experienced bone thinning. This study will explore the problem of bone thinning in children taking tenofovir DF in combination with highly active antiretroviral therapy (HAART). HIV-infected patients from 4 to 20 years old who are taking tenofovir DF or for whom tenofovir DF treatment has been recommended may be eligible for this 3-year study. Participants take tenofovir DF every day in addition to their antiretroviral therapy. They have frequent follow-up visits for tests and procedures as follows:

• Study days 0, 2, and 4: blood tests.
• Screening and every study visit starting day 6: Physical exam, medical history, blood and urine tests.
• Baseline and every 48 weeks: Dental and eye examinations, kidney ultrasound, tuberculin skin testing, chest x-ray, electrocardiogram and echocardiogram, computed tomography (CT) scan, neuropsychological testing and neurologic assessment.
• The bone age hand x-rays are done every 24 weeks, unless the growth plates are fused (i.e. the child has stopped growing)
• DEXAs are done at 0, 12, 24 weeks and every 24 weeks thereafter. Dual energy x-ray absorptionometry (DEXA) scan is used to assess bone density. The patient lies still on a table while the spine and hip are scanned using a small amount of radiation. Only the spine and hip are scanned in the DEXA scan test.
• Baseline and week 24: Optional bone biopsy. Some patients are asked to undergo a bone biopsy to better understand the effect of Tenofovir DF on bone. For the procedure, the child is given a sedative. The skin over the hipbone is numbed with a small needle, a small incision is made and a larger needle is inserted into the bone. Some of the bone tissue is withdrawn through the needle and the incision is closed.
• Possible lumbar puncture (spinal tap): This optional procedure analyzes cerebrospinal fluid (CSF), the fluid that bathes the brain and spinal cord. The patient is given a local anesthetic and a needle is inserted into the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle. There is no specific schedule for this procedure if the patient opts for it. Patients who are benefiting from tenofovir DF therapy but show signs of bone effects are offered treatment with pamidronate (Aredia), a drug used to treat hypercalcemia (too much calcium in the blood). Patients who stop taking tenofovir DF because of bone toxicity continue to be followed on the regular study schedule. Those who stop the drug for toxicity other than bone toxicity or for toxicity not related to tenofovir DF are followed every 4 weeks until their laboratory test results improve.

Conditions

HIV Infections

Keywords

Drug Resistance; HAART; Pamidronate; Osteopenia; Pediatric; HIV; Pediatrics; Treatment Experienced

Interventions

Eye exam PROCEDURE

Oral exam PROCEDURE

CT scan PROCEDURE

Neuropsychological testing PROCEDURE

Electrocardiogram PROCEDURE

Echocardiogram PROCEDURE

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-infected children between the ages of 4 years and less than 21 years.
• Clinical decision has been made to start the patient on tenofovir DF-containing antiretroviral regimen
• BSA greater than or equal to 0.85 m2
• Sexually active patients must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.
• Not pregnant or breast feeding
• OH-Vitamin D level greater than 20 ng/ml (supplementation allowed)
• Less than or equal to grade 1 serum calcium or ionized calcium (supplementation allowed)
• AST and ALT less than or equal to 7.5 times the upper limit of normal
• Age-adjusted normal serum creatinine OR a creatinine clearance greater than or equal to 70 mL/min/1.73.
• Informed consent: patient, parent or legal guardian must sign the study informed consent to document their understanding of the investigational nature and the risks of the study before any protocol-related studies are performed.
• HIV-infected children between the ages of 4 years and less than 21 years.
• Current tenofovir DF-containing antiretroviral regimen was started less than 6 months ago
• Baseline DEXA for L-spine BMD is available and was performed less than six months prior to or within the first week of starting tenofovir DF
• BSA greater than or equal to 0.85 m2
• Sexually active patients must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Sleasman JW, Nelson RP, Goodenow MM, Wilfret D, Hutson A, Baseler M, Zuckerman J, Pizzo PA, Mueller BU. Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages. J Pediatr. 1999 May;134(5):597-606. doi: 10.1016/s0022-3476(99)70247-7.

  PMID: 10228296 BACKGROUND

• Gortmaker SL, Hughes M, Cervia J, Brady M, Johnson GM, Seage GR 3rd, Song LY, Dankner WM, Oleske JM; Pediatric AIDS Clinical Trials Group Protocol 219 Team. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med. 2001 Nov 22;345(21):1522-8. doi: 10.1056/NEJMoa011157.

  PMID: 11794218 BACKGROUND

• Wainberg MA, Miller MD, Quan Y, Salomon H, Mulato AS, Lamy PD, Margot NA, Anton KE, Cherrington JM. In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Antivir Ther. 1999;4(2):87-94. doi: 10.1177/135965359900400205.

  PMID: 10682153 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Bone Diseases, Metabolic

Interventions

Diagnosis, Oral; Neuropsychological Tests

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dentistry; Psychological Tests; Behavioral Disciplines and Activities

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: July 23, 2004
• First Posted: July 26, 2004
• Study Start: June 1, 2004
• Study Completion: May 1, 2006
• Last Updated: March 4, 2008

Record last verified: 2006-05

Locations

US (1)