HIV/AIDSPhase 1NCT03917420
Quantification of Estradiol's Impact on Nucleotides in Cellular Populations of the Lower GI Tract
A Phase 1 study testing Tenofovir 300Mg Oral Tablet and Emtricitabine 200 MG in people with HIV/AIDS, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
Purpose: To Assess the impact of high and low in vivo estradiol exposure on PrEP (Pre-exposure prophylaxis) nucleotide concentrations in different cellular populations of the lower GI (gastrointestinal) tract and to quantify the relationship between estradiol, progesterone, and testosterone on PrEP nucleotide… Read more about this study
- Who is it for?
- Ages 18 to 49 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- Tenofovir 300Mg Oral Tablet and Emtricitabine 200 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Mar 2019to 4 Sep 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 49 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy cisgender pre-menopausal female participants between the ages of 18 and 49 years, inclusive on the date of screening (Healthy is defined as no irregular menstrual cycles or clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, and clinical laboratory tests.
- Regular menstrual cycles defined as at least 1 day of menses occurring every 21-35 days)
- Estimated calculated creatinine clearance (eCcr) of at least 60 mL/min by the Cockcroft-Gault formula where: eCcr (female) in mL/min = [(140 - age in years) x (weight in kg) x 0.85] / (72x serum creatinine in mg/dL).
- Negative serum pregnancy test at screening
- All participants should be using at least one of the following methods of contraception* from the screening visit through 72 hours prior to inpatient admission (at which time the women will be asked to remain abstinent until after their follow-up visit):
- Non continuous systemic hormonal contraceptives that permit intermittent menstruation
Show all 17Show fewer
- IUD (non-hormonal intrauterine device) placed at least 1 month prior to study enrollment
- Bilateral tubal ligation (Sterilization)
- Vasectomized male partners
- Condom + Spermicide
- *Unless engaged in sexual activity with female only sex partners or abstinent for at least 3 months prior with no intention of becoming sexually active during the study period. Any history of recent or present concomitant male sex partners will be addressed and ruled out in the context of screening participants for eligibility for the protocol
- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
- Subject must be willing to abstain from sexual intercourse, and all and intrarectal objects and products for at least 72 hours prior to Sampling #1 until study completion.
- Subject must be HIV-1 and Hepatitis B and C negative as documented on screening labs.
- Subject must not be actively involved in the conception process and must be non-lactating.
- Subject must be able to swallow pills and have no allergies to any component of the study product
Who cannot join
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including documented drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
- Participants with a history of hysterectomy
- Participants who are pregnant, possibly pregnant or lactating
- History of febrile illness within five days prior to first dose.
- Any condition possibly affecting drug absorption (eg, gastrectomy or other significant alterations of the gastrointestinal tract)
- A positive urine drug screen.
Show all 15Show fewer
- An untreated-positive test for syphilis, gonorrhea, or Chlamydia at screening.
- Any clinically relevant laboratory chemistry or hematology result Grade 2 or greater according to the Division of AIDS Laboratory Grading Tables
- Treatment with an investigational drug within 4 months preceding the first dose of study product.
- History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) per week.
- Participation in a clinical trial involving rectal biopsies within 6 months preceding the first dose of trial medication.
- Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.
- Any condition which, in the opinion of the investigator, is likely to interfere with follow-up or ability to take the study medication appropriately.
- Unwilling or unable to comply with the dietary and concomitant drug restrictions in regard to study drug administration as outlined in the study procedures and prohibited medications sections.
- Women utilizing continuous hormonal contraception options such as Seasonique, injectables, implants, and hormonal IUDs
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
Official title: Quantification of Estradiol's Impact on Nucleotides in Different Cellular Populations of the Lower Gastrointestinal Tract
Purpose: To Assess the impact of high and low in vivo estradiol exposure on PrEP (Pre-exposure prophylaxis) nucleotide concentrations in different cellular populations of the lower GI (gastrointestinal) tract and to quantify the relationship between estradiol, progesterone, and testosterone on PrEP nucleotide concentrations in rectal and peripheral blood mononuclear cells. As well as the relationship between estradiol, progesterone, and testosterone on PrEP concentrations in plasma.
Participants: Healthy, cisgender female, volunteers, aged 18-49 inclusive on the date of screening with an intact gastrointestinal system and regular menstrual cycle.
Procedures (methods): Participants will take a single daily dose of study drug for five days before each sampling visit. The visits will be scheduled during the early follicular phase of the menstrual cycle (approximately days 2-5 after the first day of menses, Visit 1) when estradiol is predicted to be the lowest and the late follicular phase (approximately days 12-15 after the first day of menses, Visit 2) when estradiol is predicted to be highest. Samples of blood, rectal cells, and rectal tissue will be collected at both Visits 1 and 2. All participants will complete a follow-up safety visit within 14 days of completing study sampling.
Read the detailed description
Participants will be enrolled, and sampling visits will be scheduled to correspond with their menstrual cycles. Five days prior to the first scheduled sampling visit, participants will come to the clinic to have a repeat urine pregnancy test performed to verify eligibility. After verification, participants will be given a single dose of the study medication, Truvada®. Study staff will witness the dose and assess for any adverse reactions post dose. Participants will be sent home with a supply of 4 additional doses of Truvada® for them to take at scheduled times for the next 4 days with study staff observing via video call. Study staff will assess for adverse events during each dosing call. Starting 72 hours before each sampling visit, participants will be required to switch to a low fiber diet and abstain from inserting anything rectally. Twelve hours prior to each sampling visit, participants will be required to abide by a clear liquid diet. Participants will be seen as an outpatient at the Clinical Translational Research Center (CTRC) at University of North Carolina at Chapel Hill (UNC) for these sampling visits. At these visits, participants will have blood samples drawn to measure peripheral blood mononuclear cells and serum hormone concentrations. Participants will also have rectal cells collected via cytobrush and rectal tissue collected via rectal biopsy. After all samples have been collected, participants will be evaluated for adverse events and be discharged. Within 14 days of completion of the second sampling visit, for a follow-up visit. At this visit, blood will be obtained to check safety labs.
- Conditions
- HIV/AIDS
- Being tested
- Tenofovir 300Mg Oral Tablet, Emtricitabine 200 MG
- 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.
Tenofovir 300Mg Oral TabletDrug
Also called Truvada
Once daily dose of the combo tab x 5 days pre-sampling
Emtricitabine 200 MGDrug
Also called Truvada
Once daily dose of the combo tab x 5 days pre-sampling
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir/Emtricitabine | Experimental | Participants will take 5 once daily doses above noted combination tab at 200mg/300mg before each sampling visit Receives: Drug: Tenofovir 300Mg Oral Tablet; Drug: Emtricitabine 200 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Tenofovir Diphosphate Concentrations in Mixed Rectal Cells During the Early (Low Estradiol) Follicular Phases of the Menstrual Cycle.
Average tenofovir diphosphate concentrations measured in mixed rectal cells collected via cytobrush during the early (low estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells.
Measured: Days 2-5
Average Tenofovir Diphosphate Concentrations Measured in Mixed Rectal Cells During the Late (High Estradiol) Follicular Phases of the Menstrual Cycle.
Average tenofovir diphosphate concentrations measured in mixed rectal cells collected via cytobrush during the late (high estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells
Measured: Days 12-15
Average Emtricitabine Triphosphate Concentrations Measured in Mixed Rectal Cells During the Early (Low Estradiol) Follicular Phases of the Menstrual Cycle.
Average emtricitabine triphosphate concentrations measured in mixed rectal cells collected via cytobrush during the early (low estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells.
Measured: Days 2-5
Average Emtricitabine Triphosphate Concentrations Measured in Mixed Rectal Cells During the Late (High Estradiol) Follicular Phases of the Menstrual Cycle.
Average emtricitabine triphosphate concentrations measured in mixed rectal cells collected via cytobrush during the late (high estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells.
Measured: Days 12-15
Secondary outcomes (7)
Average Estradiol Concentrations in Serum.
Average estradiol concentrations in serum reported in pg/mL
Measured: Day 5
Average Progesterone Concentrations in Serum.
Average progesterone concentrations in serum measured in ng/mL.
Measured: Day 5
Average Testosterone Concentrations in Serum.
Average testosterone concentrations in serum measured in ng/mL
Measured: Day 5
Average Tenofovir Diphosphate Concentrations in Peripheral Blood Mononuclear Cells.
Average tenofovir diphosphate concentrations in peripheral blood mononuclear cells reported in Fmol/million cells.
Measured: Day 5
Average Emtricitabine Concentrations in Peripheral Blood Mononuclear Cells.
Average emtricitabine concentrations in peripheral blood mononuclear cells reported in Fmol/million cells.
Measured: Day 5
Average Tenofovir Concentrations in Plasma.
Average tenofovir concentrations in plasma reported in ng/mL.
Measured: Day 5
Average Emtricitabine Concentrations in Plasma.
Average emtricitabine concentrations in plasma reported in ng/mL.
Measured: Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2019
- Study start26 Mar 2019
- Primary completion4 Sep 2019
- Study completion4 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe 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 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mackenzie Cottrell, PharmD, MS, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03917420
- Sponsor's protocol ID
- 19-0333
- Other IDs
- R21AI145646
- Status last verified
- Nov 2019
- First submitted
- 11 Apr 2019
- Last updated
- 12 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Response to individual request for raw data. Any resulting publication from this proposal will include the principle investigator or a co-investigator listed on the application as corresponding author. Raw de-identified datasets will be shared with requesting scientists at the discretion of principle investigator to foster scientific openness in an ethical and responsible manner.
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantification of Estradiol's Impact on Nucleotides in Different Cellular Populations of the Lower Gastrointestinal Tract
- ClinicalTrials.gov ID
- NCT03917420
- Acronym / sponsor ID
- 19-0333
- Conditions
- HIV/AIDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 26 Mar 2019 (actual)
- Primary completion
- 4 Sep 2019 (actual)
- Study completion
- 4 Sep 2019 (actual)
- First posted
- 17 Apr 2019 (actual)
- Results
- Posted 12 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Purpose: To Assess the impact of high and low in vivo estradiol exposure on PrEP (Pre-exposure prophylaxis) nucleotide concentrations in different cellular populations of the lower GI (gastrointestinal) tract and to quantify the relationship between estradiol, progesterone, and testosterone on PrEP nucleotide concentrations in rectal and peripheral blood mononuclear cells. As well as the relationship between estradiol, progesterone, and testosterone on PrEP concentrations in plasma.
Participants: Healthy, cisgender female, volunteers, aged 18-49 inclusive on the date of screening with an intact gastrointestinal system and regular menstrual cycle.
Procedures (methods): Participants will take a single daily dose of study drug for five days before each sampling visit. The visits will be scheduled during the early follicular phase of the menstrual cycle (approximately days 2-5 after the first day of menses, Visit 1) when estradiol is predicted to be the lowest and the late follicular phase (approximately days 12-15 after the first day of menses, Visit 2) when estradiol is predicted to be highest. Samples of blood, rectal cells, and rectal tissue will be collected at both Visits 1 and 2. All participants will complete a follow-up safety visit within 14 days of completing study sampling.
Detailed description
Participants will be enrolled, and sampling visits will be scheduled to correspond with their menstrual cycles. Five days prior to the first scheduled sampling visit, participants will come to the clinic to have a repeat urine pregnancy test performed to verify eligibility. After verification, participants will be given a single dose of the study medication, Truvada®. Study staff will witness the dose and assess for any adverse reactions post dose. Participants will be sent home with a supply of 4 additional doses of Truvada® for them to take at scheduled times for the next 4 days with study staff observing via video call. Study staff will assess for adverse events during each dosing call. Starting 72 hours before each sampling visit, participants will be required to switch to a low fiber diet and abstain from inserting anything rectally. Twelve hours prior to each sampling visit, participants will be required to abide by a clear liquid diet. Participants will be seen as an outpatient at the Clinical Translational Research Center (CTRC) at University of North Carolina at Chapel Hill (UNC) for these sampling visits. At these visits, participants will have blood samples drawn to measure peripheral blood mononuclear cells and serum hormone concentrations. Participants will also have rectal cells collected via cytobrush and rectal tissue collected via rectal biopsy. After all samples have been collected, participants will be evaluated for adverse events and be discharged. Within 14 days of completion of the second sampling visit, for a follow-up visit. At this visit, blood will be obtained to check safety labs.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tenofovir/Emtricitabine | Experimental | Drug: Tenofovir 300Mg Oral Tablet, Drug: Emtricitabine 200 MGParticipants will take 5 once daily doses above noted combination tab at 200mg/300mg before each sampling visit |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Healthy cisgender pre-menopausal female participants between the ages of 18 and 49 years, inclusive on the date of screening (Healthy is defined as no irregular menstrual cycles or clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, and clinical laboratory tests.
- Regular menstrual cycles defined as at least 1 day of menses occurring every 21-35 days)
- Estimated calculated creatinine clearance (eCcr) of at least 60 mL/min by the Cockcroft-Gault formula where: eCcr (female) in mL/min = [(140 - age in years) x (weight in kg) x 0.85] / (72x serum creatinine in mg/dL).
- Negative serum pregnancy test at screening
- All participants should be using at least one of the following methods of contraception* from the screening visit through 72 hours prior to inpatient admission (at which time the women will be asked to remain abstinent until after their follow-up visit):
Key exclusion criteria (15 listed)
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including documented drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
- Participants with a history of hysterectomy
- Participants who are pregnant, possibly pregnant or lactating
- History of febrile illness within five days prior to first dose.
- Any condition possibly affecting drug absorption (eg, gastrectomy or other significant alterations of the gastrointestinal tract)
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 |
|---|---|---|
| Tenofovir 300Mg Oral TabletAlso: TruvadaOnce daily dose of the combo tab x 5 days pre-sampling | Drug | Tenofovir/Emtricitabine |
| Emtricitabine 200 MGAlso: TruvadaOnce daily dose of the combo tab x 5 days pre-sampling | Drug | Tenofovir/Emtricitabine |
Primary outcome
Average Tenofovir Diphosphate Concentrations in Mixed Rectal Cells During the Early (Low Estradiol) Follicular Phases of the Menstrual Cycle.
Time frame: Days 2-5
Average tenofovir diphosphate concentrations measured in mixed rectal cells collected via cytobrush during the early (low estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells.
Average Tenofovir Diphosphate Concentrations Measured in Mixed Rectal Cells During the Late (High Estradiol) Follicular Phases of the Menstrual Cycle.
Time frame: Days 12-15
Average tenofovir diphosphate concentrations measured in mixed rectal cells collected via cytobrush during the late (high estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells
Average Emtricitabine Triphosphate Concentrations Measured in Mixed Rectal Cells During the Early (Low Estradiol) Follicular Phases of the Menstrual Cycle.
Time frame: Days 2-5
Average emtricitabine triphosphate concentrations measured in mixed rectal cells collected via cytobrush during the early (low estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells.
Average Emtricitabine Triphosphate Concentrations Measured in Mixed Rectal Cells During the Late (High Estradiol) Follicular Phases of the Menstrual Cycle.
Time frame: Days 12-15
Average emtricitabine triphosphate concentrations measured in mixed rectal cells collected via cytobrush during the late (high estradiol) follicular phases of the menstrual cycle reported in Fmol/million cells.
7 secondary outcomes
Average Estradiol Concentrations in Serum.
Time frame: Day 5
Average Progesterone Concentrations in Serum.
Time frame: Day 5
Average Testosterone Concentrations in Serum.
Time frame: Day 5
Average Tenofovir Diphosphate Concentrations in Peripheral Blood Mononuclear Cells.
Time frame: Day 5
Average Emtricitabine Concentrations in Peripheral Blood Mononuclear Cells.
Time frame: Day 5
Average Tenofovir Concentrations in Plasma.
Time frame: Day 5
Average Emtricitabine Concentrations in Plasma.
Time frame: Day 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Response to individual request for raw data. Any resulting publication from this proposal will include the principle investigator or a co-investigator listed on the application as corresponding author. Raw de-identified datasets will be shared with requesting scientists at the discretion of principle investigator to foster scientific openness in an ethical and responsible manner.
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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.
Mackenzie Cottrell, PharmD, MS principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tenofovir 300Mg Oral Tablet and Emtricitabine 200 MG in people with HIV/AIDS, run by University of North Carolina, Chapel Hill 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 17 inclusion and 15 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 12 Apr 2023. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Average Tenofovir Diphosphate Concentrations in Mixed Rectal Cells During the Early (Low Estradiol) Follicular Phases of the Menstrual Cycle. (time frame: Days 2-5). The study lists 4 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 12 Apr 2023.