Measuring and Monitoring Adherence to ART With Pill Ingestible Sensor System

NCT ID: NCT02797262

Last Updated: 2021-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2020-10-15

Brief 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. 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.

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.

Conditions

HIV/AIDS; Medication Adherence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Intervention

Building 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.

Group Type: EXPERIMENTAL

Proteus digital health feedback (PDHF) system

Intervention Type: DEVICE

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).

Control

UC 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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Proteus digital health feedback (PDHF) system

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).

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

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

• Minimum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Honghu Liu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Honghu Liu, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

LA BioMed

Los Angeles, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37401993 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R01MH110056

Identifier Type: NIH

Identifier Source: org_study_id

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