Measuring and Monitoring Adherence to ART With Pill Ingestible Sensor System

NCT02797262 | Completed Results DMC FDA Device

• 1 other identifier: 1R01MH110056
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV/AIDS; Medication Adherence

Outcome Measures

Primary Outcomes (3)

• 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.

  Adherence to ART measured by PDHF system for 16 weeks

• 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.

  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.

• 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.

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

Secondary Outcomes (2)

• Viral Load

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

• Cluster of Differentiation 4 (CD4)

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

Study Arms (2)

Intervention

EXPERIMENTAL

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.

Device: Proteus digital health feedback (PDHF) system

Control

NO INTERVENTION

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.

Interventions

Proteus digital health feedback (PDHF) system 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).

Intervention

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Yale University: collaborator
• University of Nebraska: collaborator

Study Sites (1)

LA BioMed

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• 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.

  PMID: 37401993 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Medication Adherence

Interventions

Drug Delivery Systems

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Limitations and Caveats

This study included a selected group of individuals willing to participate in the trial. Besides, it was designed as a pilot study in a randomized fashion to gather early information regarding this intervention in HIV-infected individuals. As a result, the sample size was relatively small.

Results Point of Contact

• Title: Research Scientist
• Organization: University of California, Los Angeles

statue22@gmail.com

3105917541

Study Officials

• Honghu Liu, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 13, 2016
• Study Start: September 1, 2015
• Primary Completion: October 15, 2020
• Study Completion: October 15, 2020
• Last Updated: December 20, 2021
• Results First Posted: December 20, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share

Locations

US (1)