HIV InfectionsPhase 2NCT00088309
Effect of Tenofovir DF on Bone Metabolism in Children
A Phase 2 study testing Eye exam, Oral exam and CT scan in people with HIV Infections, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV Infections
- What is being tested?
- Eye exam, Oral exam and CT scan
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2004to May 2006
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
INCLUSION CRITERIA: Cohort 1 - patients about to start tenofovir DF
- 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
- 25-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.
INCLUSION CRITERIA: Cohort 2 - patients already being treated with tenofovir DF who have baseline DEXA available
- 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.
- Not pregnant or breast feeding
- 25-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.
INCLUSION CRITERIA: Cohort 3 - patients already being treated with an antiretroviral regimen that includes tenofovir DF who DO NOT have baseline DEXA available
- HIV-infected children between the ages of 4 years and less than 21 years.
- Current antiretroviral regimen includes tenofovir DF
- Baseline (within prior 6 months) DEXA for L-spine BMD is NOT available
- 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
- 25-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 (see table below) 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.
INCLUSION CRITERIA: Eligibility criteria for pamidronate therapy (after enrollment on protocol)
One of the following while on tenofovirDF-containing antiretroviral regimen:
- Greater than 6% loss in L-spine BMD in the presence of a BMD Z score less than -2.5 at 6 months compared to baseline
- Minimal trauma fracture
- BMD Z-score less than -3
AND
One of the following while on tenofovirDF-containing antiretroviral regimen:
- Greater than or equal to 0.5 log decrease in VL from baseline
- Greater than or equal to 25% increase in absolute CD4 count from baseline
Improvement in HIV-related signs or symptoms
OR
BMD Z-score less than -3 (i.e., pamidronate therapy will also be considered for subjects whose BMD Z score is less than -3 at baseline)
- Age-adjusted normal serum creatinine (see table below) OR a creatinine clearance greater than or equal to 70 mL/min/1.73.
- Less than or equal to grade 1 serum phosphate, magnesium, and potassium (supplementation allowed)
- Not pregnant or breast feeding
- No history of hypersensitivity to bisphosphonates
INCLUSION CRITERIA: Eligibility criteria for bone biopsy (after enrollment on protocol)
- No history of bleeding abnormality
- No history of hypersensitivity or intolerance to tetracycline or related drugs
- Normal CBC and PT/PTT
- BMD Z-score greater than -3
- Informed consent: patient, parent or legal guardian must sign a separate informed consent to document their understanding of the investigational nature and the risks of the bone biopsy.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: Tenofovir Disoproxil Fumarate Salvage Therapy in HIV-Infected Children and a Study of Its Effect on Bone Metabolism
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.
Read more
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.
Read the 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 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.
- Conditions
- HIV Infections
- Being tested
- Eye exam, Oral exam, CT scan, Neuropsychological testing, Electrocardiogram
- Keywords
- Drug Resistance, HAART, Pamidronate, Osteopenia, Pediatric, HIV, Pediatrics, Treatment Experienced
- Medical subject headings
- HIV Infections, Bone Diseases, Metabolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eye examProcedure or surgery
Oral examProcedure or surgery
CT scanProcedure or surgery
Neuropsychological testingProcedure or surgery
ElectrocardiogramProcedure or surgery
EchocardiogramProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2004 (estimated)
- Study startJun 2004
- Study completionMay 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00088309
- Sponsor's protocol ID
- 040234
- Other IDs
- 04-C-0234
- Status last verified
- May 2006
- First submitted
- 23 Jul 2004
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
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.
PubMed 10228296Gortmaker 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.
PubMed 11794218Wainberg 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.
PubMed 10682153
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tenofovir Disoproxil Fumarate Salvage Therapy in HIV-Infected Children and a Study of Its Effect on Bone Metabolism
- ClinicalTrials.gov ID
- NCT00088309
- Acronym / sponsor ID
- 040234
- Conditions
- HIV Infections
- Keywords
- Drug Resistance, HAART, Pamidronate, Osteopenia, Pediatric, HIV, Pediatrics, Treatment Experienced
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2004
- Study completion
- May 2006
- First posted
- 26 Jul 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eye exam | Procedure or surgery | – |
| Oral exam | Procedure or surgery | – |
| CT scan | Procedure or surgery | – |
| Neuropsychological testing | Procedure or surgery | – |
| Electrocardiogram | Procedure or surgery | – |
| Echocardiogram | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 10228296Sleasman 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.
- Background: PubMed 11794218Gortmaker 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.
- Background: PubMed 10682153Wainberg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eye exam, Oral exam and CT scan in people with HIV Infections, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00088309, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.