Track topics on Twitter Track topics that are important to you
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 Some of the bone tissue is withdrawn through the needle and the incision is closed.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.
Tenofovir disoproxil fumarate (TDF) was approved for the treatment of HIV-infected adults in October 2001. In November 2001, we began enrollment to our phase I/II study of tenofovir DF in HIV-infected children (02-C-0006). That study has completed enrollment. The virologic and immunologic responses seen on that study in a group of heavily treatment-experienced children with multidrug resistant HIV were surprisingly good. The drug was well tolerated, but significant decreases in bone mineral density were seen in a minority of patients.
With the current study we will enroll and systematically investigate HIV-infected children for whom tenofovir DF is being used as part of salvage combination HIV therapy. The primary objective of the study is to characterize the change in bone mineral density (BMD), as measured by lumbar spine dual-energy x-ray absorptiometry (DEXA), during and following treatment with tenofovir DF-containing antiretroviral therapy in HIV-infected children. The study will enroll 3 cohorts of children: 1) HIV-infected children about to start a tenofovir DF-containing antiretroviral regimen, 2) HIV-infected children already on tenofovir DF with available baseline DEXA results, and 3) HIV-infected children already on tenofovir DF but without baseline DEXA results who will come here for investigations of bone metabolism. Studies of bone metabolism will include periodic measurements of serum and urine calcium and phosphorus, PTH and vitamin D levels, bone resorption markers (urinary collagen cross-linked N-telopeptide and free deoxypyridinoline), bone formation markers (serum osteocalcin and bone specific alkaline phosphatase), IGF-1 levels, bone age, and DEXA scans. Patients about to start tenofovir DF (cohort 1) will be offered the option of having a transiliac crest core bone biopsy with tetracycline labeling performed at baseline and at 6 months to assess static and dynamic parameters of bone quality and turnover (histomorphometry). Subjects with substantial presumed tenofovir DF-related bone toxicity who are deriving benefit from their tenofovir DF-containing antiretroviral drug regimen will be offered the option of pamidronate therapy. The effects of pamidronate treatment on bone toxicity associated with tenofovir DF in these patients will be assessed in an exploratory fashion. It is expected that up to 40 patients with baseline BMD measurements will be enrolled onto this protocol. An additional 10 patients who are undergoing tenofovir DF treatment but who did not receive baseline BMD measurements will also be permitted to enroll in order to contribute to the data used to characterize changes in toxicity.
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
Eye exam, Oral exam, CT scan, Neuropsychological testing, Electrocardiogram, Echocardiogram
National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
Published on BioPortfolio: 2014-07-24T14:33:14-0400
This research study aims to improve the standard exam called Focused Assessment with Sonography in Trauma (FAST). The FAST exam is an ultrasound test used to identify an abdominal bleed. T...
Background: - Some people with gastrointestinal or ovarian cancer also have ascites. That is free fluid built up in the abdomen. Researchers want to see if a new drug can affect some of t...
The investigators will enroll and scan normal eyes of healthy individuals using the Spectralis OCT. Each scan is graded on a scale of 0-40, with 0 representing the lowest quality and 40 th...
The study is trying to prove that the history and physical exam (H&P) in the emergency department is the most important tool in exam of patients. The investigator is attempting to correla...
To demonstrate that the Icare tonometer does not alter Keratometry readings, topography, or corneal staining. This would therefore allow intraocular pressure (IOP) testing to be done at an...
By treating each examination as a polytomous item and a grade that a student achieved in the exam as a score on the item, the partial credit model (PCM) has been used to analyse data from examinations...
Many factors impact the performance of graduating residents on certification exams. It is thought that most factors are related to the individual candidate's ability, motivation, and work ethic. Less ...
The shoulder is a complex joint, with a wide range of motion and functional demands. An understanding of the intricate network of bony, ligamentous, muscular, and neurovascular anatomy is required in ...
To analyze critically the reasons for regulating a National Licensure Exam for Brazilian Nurses (NLEXB-N).
To assess current approaches to teaching the physical exam to preclerkship students at U.S. medical schools.
A neuropsychological test designed to assess different memory functions. It may incorporate an optional cognitive exam (Brief Cognitive Status Exam) that helps to assess memory related cognitive function.
Gray matter structures of the telencephalon and limbic system in the brain, but containing widely varying definitions among authors. Included here is the cortical septal area, subcortical SEPTAL NUCLEI, and the SEPTUM PELLUCIDUM. Many authorities consider the septal region to be made up of the septal area and the septal nuclei, but excluding the septum pellucidum. (Anthoney, Neuroanatomy and the Neurologic Exam, 1994, pp485-489; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (November 18, 1998)).
The use of combination of imaging techniques or platforms (e.g., MRI SCAN and PET SCAN) encompassing aspects of anatomical, functional, or molecular imaging methods.
A series of tests designed to assess neuropsychological function. The battery is used to diagnose specific cerebral dysfunction and also to determine lateralization.
Size, shape, and length of ECG parts, including waves, intervals, duration, and segments. Some heart-related conditions can be characterized by specific set of electrocardiogram patterns.
Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...