Human Immunodeficiency VirusNCT02134431
Relationship of Tenofovir With HIV-1 Suppression in ex Vivo Tissue in Adolescents
An observational study of Human Immunodeficiency Virus, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Microbicides are topical medicines that can prevent infection by Human Immunodeficiency Virus (HIV). Microbicide medicine has yet to be studied in adolescents, a key group that is becoming infected with HIV all over the world. Read more about this study
- Who is it for?
- Ages 10 to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Human Immunodeficiency Virus
- What is being tested?
- flexible sigmoidoscopy or colonoscopy with biopsies
- Type of treatment
- Pill or oral medicine, Medical device
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Jun 2015
- Phase
- Observational
- 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 10 to 21 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: HIV positive adolescents already taking tenofovir in their antiretroviral regimen. Must be 10-14 years (n=6) and 18-21 years (n=6). HIV negative adolescents who are otherwise healthy ages10-14 years (n=6) and 18-21 years (n=6). Recruitment will be voluntary from the city/community and outpatient clinics.
Who may be able to join
- Age >/= 10 years and </= 14 years and age </= 18 years and </= 21 years.
- Willing and able to communicate in English.
- Willing and able to provide written informed consent or assent to take part in the study (where required, parent/guardian must provide consent).
- Willing and able to provide adequate information for locator purposes.
- Understand and agree to local sexually transmitted infections (STI) reporting requirements.
- HIV-negative or -positive as documented in prior serologic testing or per report, and willing to undergo repeat HIV testing.
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- Willing and able to not take aspirin, any aspirin containing medications, or non-steroidal anti-inflammatory drugs for at least 72 hours before and 72 hours after flexible sigmoidoscopy.
- All female patients of childbearing potential (post-menarche) must be willing to undergo urine pregnancy testing at screening.
- Must be in general good health, including normal renal function.
- Subjects <18 years old must be scheduled for a clinically indicated colonoscopy or flexible sigmoidoscopy with biopsies.
- HIV-positive participants only (Aim 1):
- Must have recent HIV polymerase chain reaction (PCR) documented in the last 6-12 months by verbal report
- Must have tenofovir in chronic cART regimen (>/= 1 month).
- Be reportedly compliant.
- CD4 T cells >250/cmm
Who cannot join
- Known history of inflammatory bowel disease.
- Abnormalities of the colorectal mucosa, or significant colorectal symptom(s) which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids).
- Evidence of any known enteric infection at the time of study visit.
- Participant-reported symptoms and/or clinical or laboratory diagnosis of active and symptomatic rectal infection (gonorrhea, Chlamydia, syphilis, clinically active perineal HSV).
- Note: Allow one re-screening after documented treatment (30 days) in cases of gonorrhea/chlamydia (GC/CT) identified at screening.
- Pregnancy.
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- Subjects with other poorly controlled medical conditions (e.g. diabetes, congestive heart failure).
- Chronic renal disease (BUN and serum creatinine >1.5 times the upper normal limit).
- History or presence of impaired gastrointestinal motility, or history of extensive small bowel resection (greater than half the length of the small intestine).
- Use of warfarin or heparin.
- Use of systemic immunomodulatory medications within 4 weeks of screening.
- Use of any investigational products within 4 weeks of screening.
- Fever at time of endoscopy. Subjects can be re-scheduled at a later point after the fever is resolved.
- Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of sever, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA Clinical and Translational Research Center (CTRC)
Los Angeles, California, 90095
About this study
Official title: Dose-response Relationship of Tenofovir With HIV-1 Suppression in ex Vivo Model of Tissue Infectibility in Adolescents
Microbicides are topical medicines that can prevent infection by Human Immunodeficiency Virus (HIV). Microbicide medicine has yet to be studied in adolescents, a key group that is becoming infected with HIV all over the world. From past research, we know that at different ages people experience age-related changes in their bodies that can cause differences in how they process medications. In this study, gut tissue samples (or gut biopsies) from 12 HIV-negative volunteers will be collected. These pieces of tissue will be infected with HIV in the laboratory to develop a model that can be used to test certain drugs against the HIV infection. We can use this tissue to test a drug called tenofovir against HIV infection. We will determine whether this drug can decrease HIV infection in the gut biopsies. In this study, we will also measure HIV levels and the levels of tenofovir in gut and blood samples in 12 people who are already taking this drug. This information can determine whether levels of drug found in the gut can protect it from HIV. The results can be compared to other age groups of adolescents and adults. Subjects will undergo a common procedure called a lower endoscopy (this can be a colonoscopy or a flexible sigmoidoscopy) to obtain gut biopsy samples.
The central hypothesis is that tissue drug profiles of tenofovir (TFV) and its active component, tenofovir disoproxil fumarate (TDF), and tissue infectibility vary between younger (10-14 years old) versus older adolescents (18-21 years old), and that both differ from adults (>21 years). Specifically, younger HIV positive adolescents will have lower levels of tissue tenofovir compared to older HIV positive adolescents and adults in an age-dependent manner. Additionally, biopsies from younger HIV negative adolescents will have: 1) higher rates of infection compared to biopsies from older HIV negative adolescents infected with a lower dose of virus; and 2) lower percent suppression of tissue infectivity compared to biopsies from older HIV negative adolescents using low dose tenofovir.
- Conditions
- Human Immunodeficiency Virus
- Being tested
- flexible sigmoidoscopy or colonoscopy with biopsies
- Keywords
- HIV, tenofovir, miocrobicide, endoscopy (colonoscopy, sigmoidoscopy), adolescents, pediatrics
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
flexible sigmoidoscopy or colonoscopy with biopsiesDevice
Lower endoscopy with biopsies (specifically either colonoscopy or flexible sigmoidoscopy) in both HIV-positive subjects already on oral tenofovir , as well as HIV negative subjects. Biopsies will be taken to laboratory for quantification of HIV-1 and drug levels of tenofovir.
| Study group | Role | What they receive |
|---|---|---|
| HIV positive | HIV-positive subjects ages 10-14 years old and 18-21 years old taking tenofovir in their antiretroviral regimen.HIV positive subjects will undergo lower endoscopy (specifically either flexible sigmoidoscopy or colonoscopy) with biopsies to obtain colorectal tissue samples. HIV-1 levels and tenofovir levels in tissue will be measured. Receives: Device: flexible sigmoidoscopy or colonoscopy with biopsies | |
| HIV negative | HIV-negative subjects ages 10-14 years old and 18-21 years old. HIV negative subjects will undergo lower endoscopy (specifically either flexible sigmoidoscopy or colonoscopy) with biopsies to obtain colorectal tissue samples. These tissue samples will be pretreated with tenofovir and challenged with laboratory HIV-1. Receives: Device: flexible sigmoidoscopy or colonoscopy with biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure Cmax of tenofovir (TFV) in plasma (ng/ml) & tissue (ng/mg), tenofovir-diphosphate (TFV-DP) in tissue (fmol/mg) and PBMC (fmol/million), HIV quantified PCR (copies/ml) from tissue & plasma.
Quantification of TFV and TFV-DP drug concentrations by LC-MS/MS (Liquid chromatography-mass spectrometry/mass spectrometry), and HIV-1 viral load in colorectal biopsies, plasma, and peripheral blood mononucleated cell (PBMC) of HIV positive adolescents.
Measure TFV in plasma (ng/ml) and tissue (ng/mg). Measure TFV-DP in tissue (fmol/mg) and PBMC (fmol/million). Measure HIV quantified PCR (copies/ml) from colorectal biopsy tissues and plasma.
Measured: 1 year
establish ex vivo infectibility assay as measured by HIV-1 p24 (pg/ml) in HIV-negative biopsies infected with R5 HIV-1BaL low 10^2 TCID50 or high 10^4 TCID50 concentration
After infecting gut biopsy samples ex vivo from HIV negative subjects with either low (10^2 TCID50 ) or high (10^4 TCID50) titer of R5 HIV-BaL), supernatants will collected every 3-4 days for HIV-1 p24 (pg/ml) quantification by ELISA. This quantification will assess viral replication in biopsy tissues.
Measured: 1 year
Assess differences in percent suppression of tissue infectivity (measured by HIV-1 p24 (pg/ml)) in biopsies from younger vs older adolescents pretreated with low dose tenofovir.
Mucosal biopsies will be pretreated with low-dose tenofovir ex vivo. Pretreated biopsies will then be infected with either 10^2 TCID50 or 10^4 TCID50 R5 HIV-1BaL. Supernatants will be collected every 3-4 days over a 14 day period for HIV-1 p24 (pg/ml) by ELISA. Percent suppression of tissue infectivity in biopsies will be assessed and compared between age groups.
Measured: 1 year
Secondary outcomes (1)
Measures of tenofovir drug efficacy predicting drug levels (tissue TFV ng/mg, TFV-DP fmol/mg) necessary to suppress 50%, 90%, 95% of biopsy HIV-1 p24 (pg/ml) (EC50,90,95) will be calculated by interpolation of the dose response curve.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2014 (estimated)
- Study startMay 2014
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sue McDiarmid, MD, Principal investigator, University of California, Los Angeles, Departments of Pediatrics and Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02134431
- Sponsor's protocol ID
- UL1TR000124-1955
- Other IDs
- UL1TR000124
- Status last verified
- Mar 2017
- First submitted
- 2 May 2014
- Last updated
- 13 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-response Relationship of Tenofovir With HIV-1 Suppression in ex Vivo Model of Tissue Infectibility in Adolescents
- ClinicalTrials.gov ID
- NCT02134431
- Acronym / sponsor ID
- UL1TR000124-1955
- Conditions
- Human Immunodeficiency Virus
- Keywords
- HIV, tenofovir, miocrobicide, endoscopy (colonoscopy, sigmoidoscopy), adolescents, pediatrics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 9 May 2014 (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.
Microbicides are topical medicines that can prevent infection by Human Immunodeficiency Virus (HIV). Microbicide medicine has yet to be studied in adolescents, a key group that is becoming infected with HIV all over the world. From past research, we know that at different ages people experience age-related changes in their bodies that can cause differences in how they process medications. In this study, gut tissue samples (or gut biopsies) from 12 HIV-negative volunteers will be collected. These pieces of tissue will be infected with HIV in the laboratory to develop a model that can be used to test certain drugs against the HIV infection. We can use this tissue to test a drug called tenofovir against HIV infection. We will determine whether this drug can decrease HIV infection in the gut biopsies. In this study, we will also measure HIV levels and the levels of tenofovir in gut and blood samples in 12 people who are already taking this drug. This information can determine whether levels of drug found in the gut can protect it from HIV. The results can be compared to other age groups of adolescents and adults. Subjects will undergo a common procedure called a lower endoscopy (this can be a colonoscopy or a flexible sigmoidoscopy) to obtain gut biopsy samples.
The central hypothesis is that tissue drug profiles of tenofovir (TFV) and its active component, tenofovir disoproxil fumarate (TDF), and tissue infectibility vary between younger (10-14 years old) versus older adolescents (18-21 years old), and that both differ from adults (>21 years). Specifically, younger HIV positive adolescents will have lower levels of tissue tenofovir compared to older HIV positive adolescents and adults in an age-dependent manner. Additionally, biopsies from younger HIV negative adolescents will have: 1) higher rates of infection compared to biopsies from older HIV negative adolescents infected with a lower dose of virus; and 2) lower percent suppression of tissue infectivity compared to biopsies from older HIV negative adolescents using low dose tenofovir.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV positive | – | Device: flexible sigmoidoscopy or colonoscopy with biopsiesHIV-positive subjects ages 10-14 years old and 18-21 years old taking tenofovir in their antiretroviral regimen.HIV positive subjects will undergo lower endoscopy (specifically either flexible sigmoidoscopy or colonoscopy) with biopsies to obtain colorectal tissue samples. HIV-1 levels and tenofovir levels in tissue will be measured. |
| HIV negative | – | Device: flexible sigmoidoscopy or colonoscopy with biopsiesHIV-negative subjects ages 10-14 years old and 18-21 years old. HIV negative subjects will undergo lower endoscopy (specifically either flexible sigmoidoscopy or colonoscopy) with biopsies to obtain colorectal tissue samples. These tissue samples will be pretreated with tenofovir and challenged with laboratory HIV-1. |
Who may qualify
- Ages
- 10 to 21 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- HIV positive adolescents already taking tenofovir in their antiretroviral regimen. Must be 10-14 years (n=6) and 18-21 years (n=6). HIV negative adolescents who are otherwise healthy ages10-14 years (n=6) and 18-21 years (n=6). Recruitment will be voluntary from the city/community and outpatient clinics.
Key inclusion criteria (15 listed)
- Age >/= 10 years and </= 14 years and age </= 18 years and </= 21 years.
- Willing and able to communicate in English.
- Willing and able to provide written informed consent or assent to take part in the study (where required, parent/guardian must provide consent).
- Willing and able to provide adequate information for locator purposes.
- Understand and agree to local sexually transmitted infections (STI) reporting requirements.
Key exclusion criteria (14 listed)
- Known history of inflammatory bowel disease.
- Abnormalities of the colorectal mucosa, or significant colorectal symptom(s) which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids).
- Evidence of any known enteric infection at the time of study visit.
- Participant-reported symptoms and/or clinical or laboratory diagnosis of active and symptomatic rectal infection (gonorrhea, Chlamydia, syphilis, clinically active perineal HSV).
- Pregnancy.
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 |
|---|---|---|
| flexible sigmoidoscopy or colonoscopy with biopsiesLower endoscopy with biopsies (specifically either colonoscopy or flexible sigmoidoscopy) in both HIV-positive subjects already on oral tenofovir , as well as HIV negative subjects. Biopsies will be taken to laboratory for quantification of HIV-1 and drug levels of tenofovir. | Device | HIV negative, HIV positive |
Primary outcome
Measure Cmax of tenofovir (TFV) in plasma (ng/ml) & tissue (ng/mg), tenofovir-diphosphate (TFV-DP) in tissue (fmol/mg) and PBMC (fmol/million), HIV quantified PCR (copies/ml) from tissue & plasma.
Time frame: 1 year
Quantification of TFV and TFV-DP drug concentrations by LC-MS/MS (Liquid chromatography-mass spectrometry/mass spectrometry), and HIV-1 viral load in colorectal biopsies, plasma, and peripheral blood mononucleated cell (PBMC) of HIV positive adolescents. Measure TFV in plasma (ng/ml) and tissue (ng/mg). Measure TFV-DP in tissue (fmol/mg) and PBMC (fmol/million). Measure HIV quantified PCR (copies/ml) from colorectal biopsy tissues and plasma.
establish ex vivo infectibility assay as measured by HIV-1 p24 (pg/ml) in HIV-negative biopsies infected with R5 HIV-1BaL low 10^2 TCID50 or high 10^4 TCID50 concentration
Time frame: 1 year
After infecting gut biopsy samples ex vivo from HIV negative subjects with either low (10^2 TCID50 ) or high (10^4 TCID50) titer of R5 HIV-BaL), supernatants will collected every 3-4 days for HIV-1 p24 (pg/ml) quantification by ELISA. This quantification will assess viral replication in biopsy tissues.
Assess differences in percent suppression of tissue infectivity (measured by HIV-1 p24 (pg/ml)) in biopsies from younger vs older adolescents pretreated with low dose tenofovir.
Time frame: 1 year
Mucosal biopsies will be pretreated with low-dose tenofovir ex vivo. Pretreated biopsies will then be infected with either 10^2 TCID50 or 10^4 TCID50 R5 HIV-1BaL. Supernatants will be collected every 3-4 days over a 14 day period for HIV-1 p24 (pg/ml) by ELISA. Percent suppression of tissue infectivity in biopsies will be assessed and compared between age groups.
1 secondary outcome
Measures of tenofovir drug efficacy predicting drug levels (tissue TFV ng/mg, TFV-DP fmol/mg) necessary to suppress 50%, 90%, 95% of biopsy HIV-1 p24 (pg/ml) (EC50,90,95) will be calculated by interpolation of the dose response curve.
Time frame: 1 year
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 13 Mar 2017.
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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.
Sue McDiarmid, MD principal investigator
University of California, Los Angeles, Departments of Pediatrics and Surgery
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Human Immunodeficiency Virus, run by University of California, Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2017. 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.
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.
What does the primary outcome measure?
Measure Cmax of tenofovir (TFV) in plasma (ng/ml) & tissue (ng/mg), tenofovir-diphosphate (TFV-DP) in tissue (fmol/mg) and PBMC (fmol/million), HIV quantified PCR (copies/ml) from tissue & plasma. (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2017.