- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04870671
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
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
14
Phase
- 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
-
-
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
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:
- Condoms
- Hormonal contraceptives
- Copper or Levonorgestrel intrauterine device (IUD)
- Sterilization of either partner
- Heterosexual abstinence
- 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 |
Intervention / Treatment |
---|---|
Experimental: High Adherence
TDF/FTC (300/200 mg), 7 pills/week.
Total of 14 pills
|
Women will take 1 pill orally according the dosing regimen of the arm to which they are assigned
Other Names:
|
Experimental: Low Adherence
TDF/FTC (300/2200 mg), 3 pills/week.
Total of 6 pills
|
Women will take 1 pill orally according the dosing regimen of the arm to which they are assigned
Other Names:
|
What is the study measuring?
Primary Outcome Measures
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
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
Investigators
- 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
- Hendrix CW, Andrade A, Bumpus NN, Kashuba AD, Marzinke MA, Moore A, Anderson PL, Bushman LR, Fuchs EJ, Wiggins I, Radebaugh C, Prince HA, Bakshi RP, Wang R, Richardson P, Shieh E, McKinstry L, Li X, Donnell D, Elharrar V, Mayer KH, Patterson KB. Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks (HPTN 066). AIDS Res Hum Retroviruses. 2016 Jan;32(1):32-43. doi: 10.1089/AID.2015.0182. Epub 2015 Oct 15.
- Donnell D, Baeten JM, Bumpus NN, Brantley J, Bangsberg DR, Haberer JE, Mujugira A, Mugo N, Ndase P, Hendrix C, Celum C. HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):340-8. doi: 10.1097/QAI.0000000000000172.
- Ruscito A, DeRosa MC. Small-Molecule Binding Aptamers: Selection Strategies, Characterization, and Applications. Front Chem. 2016 May 10;4:14. doi: 10.3389/fchem.2016.00014. eCollection 2016.
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)
March 25, 2021
Primary Completion (Actual)
January 31, 2023
Study Completion (Actual)
January 31, 2023
Study Registration Dates
First Submitted
April 23, 2021
First Submitted That Met QC Criteria
April 28, 2021
First Posted (Actual)
May 3, 2021
Study Record Updates
Last Update Posted (Actual)
January 30, 2024
Last Update Submitted That Met QC Criteria
January 4, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Slow Virus Diseases
- Urogenital Diseases
- Genital Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
- Emtricitabine
Other Study ID 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.
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