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HIV/AIDSNCT02797262

Measuring and Monitoring Adherence to ART With Pill Ingestible Sensor System

A study testing Proteus digital health feedback (PDHF) system in people with HIV/AIDS and Medication Adherence, run by University of California, Los Angeles at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Introduction of antiretroviral therapy (ART) has transformed HIV-infection from a fatal to manageable disease but adherence to ART remains critical to optimize outcomes. Existing measures of ART adherence provide only inferred measures of actual drug intake and most offer no real-time notification capability. Read more about this study

Who is it for?
Ages 17 years and older
Conditions the study is for
HIV/AIDS, Medication Adherence
What is being tested?
Proteus digital health feedback (PDHF) system
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
1 siteUnited States
Study dates
Sep 2015to 15 Oct 2020
Phase
Interventional
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 17 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • HIV-infected individuals in HIV care
  • greater than 17 years of age
  • demonstrated ability to take over-encapsulated ARVs at time of screening; able to provide informed consent
  • On ART with sub-optimal adherence estimated by either patient (self-reports < 90% adherence over last 28 days) or treating clinician (e.g., based on gaps in treatment (e.g., missed appointments) or viral load elevations within last 6 months)

Who cannot join

  • Inability to follow the study procedures manifested during the intake, as evidenced by mental confusion, disorganization, intoxication, withdrawal, risky or threatening behavior

Trial locations and contacts

1 site in 1 country.

United States1 site
  • LA BioMed

    Los Angeles, California, 90095

Other trials in United States

About this study

Introduction of antiretroviral therapy (ART) has transformed HIV-infection from a fatal to manageable disease but adherence to ART remains critical to optimize outcomes. Existing measures of ART adherence provide only inferred measures of actual drug intake and most offer no real-time notification capability. Directly observed therapy measures actual drug intake but is not practical. These limitations constrain research into medication adherence and more importantly, limit our ability to develop real-time interventions based on feasible, in vivo monitoring of adherence among HIV-infected people to facilitate medication-taking. The Proteus digital health feedback (PDHF) system, a pill ingestible sensor based adherence measuring and monitoring system developed by Proteus Digital Health, addresses these limitations. It involves use of an ingestible sensor, a tiny edible material that is over-encapsulated along with prescribed medication. The sensor is activated by ingestion and is sensed by a patch worn by the patient with an embedded monitor and sensor. The monitor sends a Bluetooth signal to a mobile device, which in turn sends an encrypted message to a central server, thus effecting real-time monitoring that a dose has been taken. The investigators propose to develop a data receiving hub and add to these components an automated text message that is sent to the patient when a dose is missed. The investigators will evaluate the feasibility, acceptability and sustainability of using the PDHF system; assess the accuracy of the PDHF system in measuring adherence to ART; and evaluate the efficacy of the PDHF system for monitoring and leveraging adherence to ART.

Read the detailed description

Introduction of antiretroviral therapy (ART) has transformed HIV-infection from a fatal to manageable disease but adherence to ART remains critical to optimize outcomes. Existing measures of ART adherence such as self-report, pill counts, electronic pill-bottle caps, and prescription refills, provide only inferred measures of actual drug intake and most offer no real-time notification capability. Directly observed therapy measures actual drug intake but is not practical. These limitations constrain research into medication adherence and more importantly, limit our ability to develop real-time interventions based on feasible, in vivo monitoring of adherence among HIV-infected people to facilitate medication-taking. The Proteus digital health feedback (PDHF) system, a pill ingestible sensor based adherence measuring and monitoring system developed by Proteus Digital Health, addresses these limitations. It involves use of an ingestible sensor, a tiny edible material that is over-encapsulated along with prescribed medication. The sensor is activated by ingestion and is sensed by a patch worn by the patient with an embedded monitor and sensor. The monitor sends a Bluetooth signal to a mobile device, which in turn sends an encrypted message to a central server, thus effecting real-time monitoring that a dose has been taken. The investigators propose to develop a data receiving hub and add to these components an automated text message that is sent to the patient when a dose is missed. The ingestible sensor and patch monitor system is already FDA-approved as safe, but has yet to be tested in HIV-infected patients in clinical setting. The first goals of this study are to confirm the bioavailability of over-encapsulated antiretrovirals (ARVs) and to pilot-test the use of the PDHF system in 15 participants prescribed ARVs to test and identify approaches that optimize the use of this measuring and monitoring system. The next goals are to determine the system's feasibility, acceptability, sustainability, accuracy and efficacy in fostering ART adherence. Feasibility, acceptability and sustainability will be assessed by patients' rating of the system and the rate of dropping off from using the system. Accuracy will be evaluated by the associations between adherence to ART measured by the PDHF system and other adherence measures such as plasma drug level concentrations of ARVs and self-report. Efficacy will be assessed by comparing adherence of participants assigned to the PDHF system and participants assigned to usual care (UC) over time, with exploratory outcomes of viral load and cluster of differentiation 4 (CD4). The investigators will recruit 120 of HIV-infected patients 18 years or older with sub-optimal adherence. Participants will be randomized to receive the PDHF system or UC for 16 weeks with monthly assessments. The durability of effects of the PDHF system after stopping the use of the system will be determined during a 12-week follow-up stage. In summary, The investigators will evaluate the feasibility, acceptability and sustainability of using the PDHF system; assess the accuracy of the PDHF system in measuring adherence to ART; and evaluate the efficacy of the PDHF system for monitoring and leveraging adherence to ART.

Being tested
Proteus digital health feedback (PDHF) system
Medical subject headings
Acquired Immunodeficiency Syndrome, Medication Adherence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Proteus digital health feedback (PDHF) systemDevice

    Building on the available Proteus devices, the investigators will design and create a PDHF system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT).

Study groups in NCT02797262
Study groupRoleWhat they receive
InterventionExperimentalBuilding on the available Proteus devices, the investigators will design and create a Proteus digital health feedback (PDHF) system to transmit the adherence data using mobile technology to allow treatment monitoring that is, direct confirmation of the type, dose, date and time of oral pharmaceutical ingestion using wirelessly observed therapy (WOT). The investigators will test overall utility (including feasibility, acceptability and sustainability) of the PDHF system, its accuracy for measuring adherence and its impact on enhancing patients' level of adherence and the effect on virologic and clinical outcomes (exploratory), the retention of its impact on keeping up with adherence and improvement of plasma HIV RNA and CD4 cell count after the 16-week usage of the PDHF system.
Receives: Device: Proteus digital health feedback (PDHF) system
ControlNo interventionUC is chosen as the control condition because it meets ethical and moral requirements to attempt treatment. Eligible patients will be randomized to one of the two conditions using a stratified urn randomization procedure to increase the likelihood of balanced allocation of prognostic variables at baseline.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adherence Measured by Sensor by Percentage of Prescribed Medications Taken

    Adherence to antiretroviral therapy (ART) measured by Proteus digital health feedback (PDHF) system for 16 weeks, including percent of prescribed medication taken.

    Measured: Adherence to ART measured by PDHF system for 16 weeks

  2. Pharmacokinetic Adherence by Integrated Pharmacokinetic Adherence Score

    The plasma concentration-time data of tenofovir (TFV) from participants who have a tenofovir alafenamide (TAF) in their regimen are used to quantify intra-patient pharmacokinetic (PK) variability as a measure of adherence. Plasma concentrations of TFV are measured by liquid chromatography/tandem mass spectrometry. A population PK model will be developed using a nonlinear mixed-effects approach with data from all the time points. The integrated PK adherence score (IPAM) will be calculated. The IPAM score ranges from 0 to 1. A high score indicates high concentration predictability and relatively higher adherence, while a low score indicates low predictability and lower adherence.

    Measured: Blood samples will be obtained in all participants before and 2 and 6 hours following an observed dose (baseline) and then at weeks 4, 8, 12, 16, 20, 24 and 28.

  3. Self-Reported Medication Adherence and "Change" Over Time

    The investigators will use a widely-used measure of self-reported adherence for percent of prescribed dose taken during the preceding seven days. This tool is easy to use and has been significantly associated with virological and immunological outcomes. Due to its potential bias, self-reported adherence will be calibrated by drug level concentration to leverage its accuracy and used in analysis when calibrated self-report adherence is appropriate to be used.

    Measured: Self-report adherence will be measured at baseline, and weeks 4, 8, 12, 16, 20, 24, and 28.

Secondary outcomes (2)
  1. Viral Load

    Viral Load will be measured at baseline, weeks 4, 8, 12, 16, and 28.

    Measured: Baseline, weeks 4, 8, 12, 16, and 28.

  2. Cluster of Differentiation 4 (CD4)

    CD4 cell count is a test that measures the number of CD4 cells (a type of the human T-lymphocyte cells) in a HIV patient's blood. The absolute CD4 cell count is measured by a simple blood test, the results of which are reported as the number of CD4 cells per cubic millimeter of blood. HIV-negative people typically have absolute CD4 cell counts between 600 and 1200 cells per cubic millimeter. HIV is a fatal infection, characterized by the targeting and destruction of CD4 cells. People with advanced HIV can have 200 or fewer CD4 cells per cubic millimeter.

    Measured: on: CD4 will be measured at baseline, weeks 4, 8, 12, 16, and 28.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2016 (estimated)
  2. Study startSep 2015
  3. Primary completion15 Oct 2020
  4. Study completion15 Oct 2020

Resources

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 N/A
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02797262
Sponsor's protocol ID
1R01MH110056
Status last verified
Dec 2021
First submitted
1 Jun 2016
Last updated
20 Dec 2021
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
Yes: De-identified individual participant data for all primary and secondary outcome measures will be made available within 6 months of study completion.

Publications

  • Wang Y, Daar ES, Huang Y, Xiong D, Shen J, Zhou L, Siqueiros L, Guerrero M, Rosen MI, Liu H. Adherence to Antiretrovirals and HIV Viral Suppression Under COVID-19 Pandemic Interruption - Findings from a Randomized Clinical Trial Using Ingestible Sensors to Monitor Adherence. AIDS Behav. 2023 Dec;27(12):4041-4051. doi: 10.1007/s10461-023-04118-9. Epub 2023 Jul 4.

    PubMed 37401993

Questions about this trial

What is this clinical trial studying?

A study testing Proteus digital health feedback (PDHF) system in people with HIV/AIDS and Medication Adherence, 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 4 inclusion and 1 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 20 Dec 2021. 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?

Yes. Results are posted in the registry (first posted 20 Dec 2021). 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?

Adherence Measured by Sensor by Percentage of Prescribed Medications Taken (time frame: Adherence to ART measured by PDHF system for 16 weeks). 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?

On the ClinicalTrials.gov record for NCT02797262, which also lists 1 linked publication.

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 20 Dec 2021.

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