Project ADHERE: Clinical Proof-of-Concept of a Tenofovir (TFV) Aptamer-Based Biosensor

January 4, 2024 updated by: Terry Jacot, Eastern Virginia Medical School

Project ADHERE: Clinical Proof-of-Concept of a Tenofovir (TFV) Aptamer-Based Biosensor for Determining Adherence Using Different Dosing Regimens of Disoproxil Fumarate/Emtricitabine (TDF/FTC)

Truvada®, an oral pill comprised of two anti-retroviral compounds, emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), is currently the only drug combination approved for pre-exposure prophylaxis (PrEP) in women exposed to high HIV risk through vaginal acquisition. Adherence to the one pill per day regimen is crucial for its effectiveness in reducing the risk of acquiring HIV. Currently, there is no available point of care diagnostic test to quickly measure blood levels of tenofovir in the clinic. This study will determine whether a tenofovir (TFV) aptamer-based biosensor (aptasensor) can detect TFV in biological fluids from women randomized to different dosing regimens representing high and low adherence.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Project ADHERE is a pilot, prospective, randomized study which will screen approximately 20 healthy, non-pregnant, HIV negative, premenopausal women (aged 18-50) at Eastern Virginia Medical School (EVMS) who are not at risk of pregnancy and are at low risk for sexually transmitted infections (STIs) in order to have approximately 14 women complete all study visits. The women will be randomized to one of two different dosing regimens of Truvada for up to 14 days. The low adherence cohort will take a total of 3 Truvada pills per week while the high adherence cohort will be assigned to take daily dosing, 7 pills per week. At screening (visit 1), we will screen women for HIV-1 and perform STI tests and serum screening for Hepatitis B and creatinine clearance prior to commencing oral PrEP, consistent with oral PrEP initiation guidelines. After screening labs return, they will come to the clinic for visit 2 when baseline blood, urine, and vaginal fluid will be collected, randomize participants to the dosing regimen, watch the participants ingest the first dose, and then direct to them to take subsequent doses in their homes. Reminder text messages will be sent to the participants to facilitate doses being taken at the same time of day upon which they will text message the coordinator after ingesting the pill. Participants will return 24 hours, 7 days, and 14 days after visit 2 for pre-dose collection of blood, urine, and vaginal fluid samples (visits 3, 4, and 5, respectively). For all visits, participants will not to take the next prescribed dose before coming to the clinic. Once samples are collected, participants will ingest the next scheduled pill. However, for the high adherence regimen, the women will take their last dose on day 14 and then come to the clinic 24 hours later on day 15 for collection of samples. Regardless of regimen, sample collection will take place no earlier than 24 hours after last dosing to prevent white coat effects. Samples will be brought to the laboratory for processing and eventual measurement of TFV levels by the TFV aptasensor. Aliquots of plasma and urine will also be analyzed by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) so sensitivity and specificity of the aptasensor can be determined. The ability of the TFV aptasensor to distinguish levels associated with high and low adherence will also be assessed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Clinical Research Center, Eastern Virginia Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age 18 to 50 years, inclusive
  • General good health (by volunteer history and per investigator judgment) without any clinically significant systemic disease (including, but not limited to significant liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, osteoporosis or bone disease, and diabetes) and with an intact gastrointestinal tract, uterus and cervix.
  • Estimated calculated creatinine clearance (eCcr) of at least 80 mL/min
  • Body Mass Index (BMI) of ≥18 and <35kg/m2; and a total body weight >45 kg (99.2 lbs)
  • Willing to give voluntary consent and sign an informed consent form
  • Willing and able to comply with protocol requirements, including swallowing tablets

  • Must be protected from pregnancy by:

    1. Condoms
    2. Hormonal contraceptives
    3. Copper or Levonorgestrel intrauterine device (IUD)
    4. Sterilization of either partner
    5. Heterosexual abstinence
    6. Same sex relationship
  • If in a relationship, must be in a mutually monogamous relationship with a partner who is not known to be HIV positive and has no known risk of STIs

Exclusion Criteria:

  • Currently pregnant
  • Currently breastfeeding or planning to breastfeed during the course of the study
  • In the last three months, diagnosed with or treated for any STI
  • Positive test for HIV, or Hepatitis B surface antigen (HBsAg)
  • Systemic use in the last two weeks or anticipated use during the study of any of the following: antiretrovirals (e.g. Viread®, Atripla®, Emtriva®, or Complera®), or drugs that may interact with TFV (e.g., protease inhibitors, anticonvulsants, antimycobacterials, St. John's Wort).
  • Participation in any other investigational trial with use of a drug/device within the last 30 days or planned participation in any other investigational trial with use of a drug/device during the study
  • Grade 2 or higher laboratory abnormality, per the 2014 update of the Division of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse Events, or clinically significant laboratory abnormality as determined by the clinician
  • Abnormal finding on laboratory or physical examination or a social or medical condition in the volunteer which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: High Adherence
TDF/FTC (300/200 mg), 7 pills/week. Total of 14 pills
Drug: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)
Women will take 1 pill orally according the dosing regimen of the arm to which they are assigned
Other Names:
  • Truvada
Experimental: Low Adherence
TDF/FTC (300/2200 mg), 3 pills/week. Total of 6 pills
Drug: Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)
Women will take 1 pill orally according the dosing regimen of the arm to which they are assigned
Other Names:
  • Truvada

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Baseline TFV (Tenofovir) Levels in Plasma
Time Frame: Baseline (pre-dose)
TFV levels will be measured by the TFV aptasensor and compared to Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) values
Baseline (pre-dose)
Levels of TFV in Plasma After Different Lengths of Time Post-first Dose
Time Frame: 1 day
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
1 day
Levels of TFV in Plasma After Different Lengths of Time Post-first Dose
Time Frame: 7 days
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
7 days
Levels of TFV in Plasma After Different Lengths of Time Post-first Dose
Time Frame: 14 days
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
14 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Baseline TFV levels in urine
Time Frame: Baseline (pre-dose)
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values (urine only)
Baseline (pre-dose)
Levels of TFV in urine after different lengths of time post-first dose
Time Frame: 24 hours
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
24 hours
Levels of TFV in urine after different lengths of time post-first dose
Time Frame: 7 days
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
7 days
Levels of TFV in urine after different lengths of time post-first dose
Time Frame: 14 days
TFV levels will be measured by the TFV aptasensor and compared to LC-MS/MS values
14 days
Baseline TFV levels in vaginal fluid
Time Frame: Baseline (pre-dose)
TFV levels will be measured by the TFV aptasensor
Baseline (pre-dose)
Levels of TFV in vaginal fluid after different lengths of time post-first dose
Time Frame: 24 hours
TFV levels will be measured by the TFV aptasensor
24 hours
Levels of TFV in vaginal fluid after different lengths of time post-first dose
Time Frame: 7 days
TFV levels will be measured by the TFV aptasensor
7 days
Levels of TFV in vaginal fluid after different lengths of time post-first dose
Time Frame: 14 days
TFV levels will be measured by the TFV aptasensor
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eastern Virginia Medical School

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Terry A Jacot, PhD, Eastern Virginia Medical School
  • Principal Investigator: Andrea R Thurman, MD, Eastern Virginia Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 25, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 23, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 3, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 30, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 19-08-FB-0195
  • 5R21AI145809-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV/AIDS

Clinical Trials on Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings