Antiviral Pharmacology and Adherence in Drug Users

March 4, 2022 updated by: University of Colorado, Denver
Approximately one half of all Americans living with Hepatitis C virus (HCV) are drug users, yet they are the least likely to receive HCV treatment. Drug users are presumed non-adherent and therefore denied potentially life-saving therapy. This assumption can only be confirmed or dispelled through prospective pharmacologic and adherence studies in this population. Such studies would be greatly enhanced by an objective, quantitative measure of adherence which does not currently exist in the HCV field. Through the work proposed in this application, sixty HIV/HCV co-infected drug users will be treated with direct acting antiviral agents (DAA) and randomized to receive directly observed DAA therapy (DOT) vs. no directly observed therapy (no-DOT). Patients randomized to no-DOT will have wirelessly observed therapy (WOT) which involves use of a portable medication dispenser that sends a signal to a server with the date and time when the dispenser is opened. In Aim 1, DAA concentrations will be compared in those randomized to DOT vs. no-DOT. DAA pharmacokinetics will also be defined accounting for clinical factors like degree of hepatic impairment and use of concomitant recreational and antiretroviral drugs. The goal is to quantify adherence in this population and the effect of variable adherence on drug concentrations. In Aim 2, DAA concentrations (plasma, cellular, hair) will be linked with adherence patterns identified using WOT and DOT. The goal is to identify a drug concentration biomarker that predicts adherence in this population. In Aim 3, the relationship between DAA adherence (as measured by WOT and DOT and drug concentrations) and rate of cure will be established. The goal is to define the degree of adherence needed for HCV cure.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

73

Phase

  • Not Applicable

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
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschutz Medical Campus

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ability to give informed consent
  • HIV-infected men and women
  • Chronic HCV infection as documented by quantifiable HCV RNA
  • HCV genotype 1, 4, 5, 6
  • 18-70 years of age
  • Willingness and ability to comply with study procedures, including DOT, WOT, and biweekly clinic visits
  • Considered an active drug user by HCV provider and self-reported drug use within the past month

Exclusion Criteria:

  • Glomerular filtration rate < 30 mL/min/1.73 m2
  • Receipt of prior HCV treatment and radiographic, histologic, or clinical evidence of cirrhosis
  • Decompensated liver disease (i.e., ascites, history of esophageal variceal bleeding, hepatic encephalopathy)
  • Medications not recommended per the SOF/LDV prescribing information (e.g., tipranavir and other P-gp inducers, tenofovir disoproxil fumarate plus cobicistat, rosuvastatin, amiodarone)
  • Any medical condition that in the opinion of the investigators will make it challenging to adhere to the study protocol, such as unstable heart disease or cancer
  • Chronic Hepatitis B virus Infection
  • For females, active pregnancy or any intent to become pregnant
  • For both sexes, an unwillingness to use contraception during the study period
  • On parole or impending sentencing

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: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Sofosbuvir/Ledipasvir with Directly Observed Therapy (DOT)
Participants randomized to vDOT will be provided a smart phone with cellular service and will be pre-programmed with the mobile phone-based video application and contact information for study personnel.
Behavioral: Directly Observed Therapy
Other Names:
  • DOT
Other: Sofosbuvir/Ledipasvir with Wirelessly Observed Therapy (WOT)
Participants on WOT will be provided the Wisepill portable medication dispenser.
Behavioral: Wirelessly Observed Therapy
Other Names:
  • WOT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Compare each individual's modeled estimate of ledipasvir and metabolites of sofosbuvir (GS-331007 and GS-331007-TP) steady state concentrations (Css) from non-linear mixed effects modeling to Css in subjects receiving DOT vs. WOT.
Time Frame: 12 weeks
12 weeks
Quantify GS-331007-TP concentrations in dried blood spots as a function of adherence (doses taken/doses prescribed).
Time Frame: 12 weeks
12 weeks
Estimate the probability of HCV cure as a function of adherence using logistic regression.
Time Frame: 24 weeks
24 weeks

Collaborators and Investigators

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

Sponsor

University of Colorado, Denver

Collaborators

National Institute on Drug Abuse (NIDA)
Gilead Sciences
Denver Health and Hospital Authority

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)

November 1, 2015

Primary Completion (Actual)

March 1, 2020

Study Completion (Actual)

June 1, 2021

Study Registration Dates

First Submitted

June 3, 2015

First Submitted That Met QC Criteria

October 7, 2015

First Posted (Estimate)

October 9, 2015

Study Record Updates

Last Update Posted (Actual)

March 8, 2022

Last Update Submitted That Met QC Criteria

March 4, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-0809
  • 1R01DA040499-01 (U.S. NIH Grant/Contract)

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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