Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00088309
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2004-07-23
Brief Title:
Effect of Tenofovir DF on Bone Metabolism in Children
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Tenofovir Disoproxil Fumarate Salvage Therapy in HIV-Infected Children and a Study of Its Effect on Bone Metabolism
Status:
COMPLETED
Status Verified Date:
2006-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 ie 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
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 ie 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
Detailed Description:
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 III 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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-C-0234 | None | None | None |