Clinical Trials

MainTitle

Improving HIV/Tuberculosis Outcomes in Irkutsk

This study is currently recruiting participants. (see Contacts and Locations)

Verified January 2019 by Scott Heysell, MD, University of Virginia

Sponsor
University of Virginia

Collaborator
National Institute on Drug Abuse (NIDA)
Scientific Center for Family Health and Human Reproduction Problems, Russia

Information provided by (Responsible Party)
Scott Heysell, MD, University of Virginia

ClinicalTrials.gov Identifier
NCT03819374

First received: January 17, 2019
Last updated: January 25, 2019
Last Verified: January 2019
History of Changes
Purpose

Purpose

The investigators propose to examine the prospective influence of substance use patterns on HIV/tuberculosis adherence, pharmacokinetics and disease progression while developing novel methods for early detection and correction of these mechanisms of treatment failure in Irkutsk. At the University of Virginia, the investigators have considerable research experience with vulnerable HIV populations and have adapted mobile phone methods for data collection of adherence, substance use, and study retention. The investigators have also begun development of colorimetric methods for pharmacokinetic monitoring that utilizes urine which may be suitable as a non-invasive sample for the unique environmental factors affecting HIV patients in Irkutsk, namely geographic remoteness and concurrent substance use

Condition
Tuberculosis
HIV Infections
Substance Use

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Improving HIV/Tuberculosis Outcomes in Irkutsk

Further study details as provided by Scott Heysell, MD, University of Virginia:

Primary Outcome Measures

  • Nonadherence as measured by clinic attendance, pharmacy refill and daily adherence response to the mHealth app will be more frequent in participants with ongoing substance use. [ Time Frame: At 12 months from enrollment nonadherence will be compared among those with a without ongoing substance use ]
    Participants will be assessed for measurements of adherence by clinic attendance, pharmacy refill at each study visit. Antiretroviral and anti-tuberculosis medication adherence is also questioned daily through the mHealth application. Additionally, a trans-renal DNA assay be measured at baseline and subsequent study visits to detect the presence of M. tuberculosis fragments in the urine.
Secondary Outcome Measures:
  • Correlation of serum mass spectrometry to urine colorimetry for AUC of anti-tuberculosis drugs [ Time Frame: 6 months after enrollment completed ]
    Urine colorimetry will be compared to conventional serum mass spectrometry for kinetics of anti-tuberculosis drugs (rifampin and levofloxacin pending the participants' drug regimen), to generate ROC at baseline for total area under the concentration curve (AUC). Urine will then be collected via limited sampling strategy at 2 and 6 months after enrollment to determine correlation with the baseline urine sample.
  • Correlation of serum mass spectrometry to urine colorimetry for peak concentration of anti-tuberculosis drugs [ Time Frame: 6 months after enrollment completed ]
    Urine colorimetry will be compared to conventional serum mass spectrometry for kinetics of anti-tuberculosis drugs (rifampin and levofloxacin pending the participants' drug regimen), to generate ROC at baseline for peak concentration (Cmax). Urine will then be collected via limited sampling strategy at 2 and 6 months after enrollment to determine correlation with the baseline urine sample.

Biospecimen Retention: Samples With DNA
Urine and Blood

Estimated Enrollment: 120
Study Start Date: April 15, 2018
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)

Detailed Description:

Subjects will be recruited at the Irkutsk Clinical Tuberculosis Hospital by trained research staff. Potential subjects are frequently diagnosed with HIV during their presentation with tuberculosis (TB) and treatment for TB begins prior to initiation of antiretrovirals for HIV. Hospital clinicians will notify research staff of potential subjects that are HIV infected, being treated for TB, have a history of substance use, and awaiting antiretroviral initiation. Prior to consent, potential subjects will be asked if they are willing to use a mobile phone as part of a research study. All subjects are consented in a private examination room by research staff. All enrolled subjects at each of the study sites are assigned individual participant identification (ID) numbers that are used for all subsequent case report forms and database.
Baseline characteristics and routine hospital laboratory data will be collected by the research staff from structured interview and review of hospital chart including demographics (age, sex, country/region of origin), CD4+ cell count and HIV viral load on admission to hospital (routine flow cytometry and Roche Amplicor version 1.5 for HIV-1 RNA levels- lower limit of detection 50 copies/mL), medical comorbidities other than HIV (diabetes, chronic kidney disease, hepatitis C or other known liver disease), and prior TB history, and anatomic site of current TB disease. Researchers will also compile a detailed substance use history and complete the HIV related quality of life survey, the Functional Assessment HIV Infection, that has been validated in the Russian setting.
Over the first 7 days of enrollment during hospitalization, the subject will receive education on the functionality of the smart phone including a short proficiency test that must be passed in order to have the mHealth application downloaded on their smartphone. In the rare instance that a subject does not own a smartphone, the study will issue a smartphone to the subject along with the dataplan. During that education period, the subject and the trained researcher will set-up the coding schema for the messages the subjects will later be texted. A preset coding schema will be available or the subject can individualize their messages with the researcher. If necessary, the researcher will explain the details of the smartphone "ownership" and data plan during the study period, how the data plan will be reissued each month, and if necessary, how the phone will be requested to be given back to the study staff after 6 months. The researchers acknowledge that some phones will not be retrieved, particularly in those subjects that die or experience permanent treatment cessation. In the situation where a subject cannot be confirmed as having died but does not present for one of the follow-up specimen collection procedures, the mHealth application will continue to send messages for the 6 month period that could record ongoing medication adherence (or non-adherence) and substance use.
Following the procedures that occur within the first 7 days of enrollment, phlebotomy and urine collection for pharmacokinetic testing will be scheduled to be performed after the patient has initiated anti-TB and antiretroviral treatment (between 2 and 8 weeks after hospitalization). Subjects remain in the hospital during this period per current clinical protocol/ standards of care. On the day of phlebotomy and urine collection, all medication will be directly administered and observed by nursing staff in the fasting state. All medications are given as a morning dose, and then venous blood samples are collected at 1, 2, 6 and optionally at 8 hours after the observed dose. A maximum of 5 ml will be obtained at each draw as up to 4 different anti-TB drugs will be required to be assayed by conventional chromatography methods. Blood will be immediately centrifuged onsite at the hospital and serum stored in sealed screw-cap tubes at -80 degrees Centigrade with the subject's participant ID number, sample ID number and study visit/time of blood draw. Batched serum specimens will be tested at the Scientific Centre in Irkutsk by chromatography/mass spectrometry. The sampling intervals allow for accurate estimates of the peak drug concentration (Cmax) and the area under the concentration curve (AUC), the two most important pharmacokinetic determinants of efficacy for the medications sampled. Urine will be collected for 24 hours (and labeled/stored as above) on the same day starting as soon as possible after medication administration. Urine will also be tested at the Scientific Centre in batch using the colorimetric assays. The first full 24 hour of urine drug concentration testing compared to the serum studies will allow adequate comparison of urinary kinetics to estimate the Cmax values from the timing of follow-up samples collected at 2 and 6 months after enrollment.
Following discharge from the hospital, subjects will be monitored for adherence by the daily messaging of the mobile health (mHealth) application and by monthly via medication refill reports from the TB Control Program. Subjects will be asked to return for follow-up visits at 2 and 6 months after enrollment. The site of follow-up will be arranged to be the TB clinic closest to where the patient resides or the clinic of the patient's request. Using the mHealth application, subjects will be texted the date, time and location of their study follow-up and the request to confirm yes/no that they will attend. Subjects unable to follow-up will be offered another time and location for follow-up, and if unable to be reached by text, then contacted using the alternative phone number(s) provided at enrollment.
At the follow-up visits researchers will administer a short symptom screening/ examination, a structured interview on substance use and medication recall assessment, then observe the subject taking their medications. During the 3-6 hours after medication administration the subject will have urine collected twice. If the subject does not have medication on hand, then another opportunity for follow-up will be arranged including the possibility of sample collection at the subject's residence. These follow-up urine specimens will not be frequent enough to calculate a full AUC, but rather an estimate of the Cmax value which we hypothesize to be most affected by patterns of substance use (alcohol and heroin).
At the completion of study procedures, an optional focus group discussion will be conducted among 30 randomly selected and gender balanced subjects to assess the feasibility of using mHealth application beyond that as a research tool.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 64 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  
Sampling Method: Probability Sample  

Study Population

HIV-infected adults initiating anti-TB and antiretroviral therapy over the course of 1 year at Irkutsk Regional TB Hospital with a history of substance use will undergo prospective adherence and substance use data collection facilitated by a population-adapted smart phone application, to assess the impact of this technology on medication adherence.

Criteria

Inclusion Criteria:

  • Adults 18-64 years of age
  • HIV infected (confirmed by medical chart review)
  • Initiating TB treatment (with anti-TB medicine)
  • Initiating HIV treatment (with antiretroviral medicine)
  • History of any substance use (confirmed by medical chart review)
  • Primary residence in Irkutsk City, Russian Federation


Exclusion Criteria:
  • Unable or unwilling to operate a smartphone
  • Pregnant at time of enrollment per lab results (urine or serum) from Medical Record
  • Prisoners Cognitively unable to provide informed consent

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03819374

Contacts

Contact:   Scott K Heysell, MD 434-243-9064 skh8r@virginia.edu
Contact:   Jennifer A White, BSN 434-982-3649 jaw9r@virginia.edu

Locations

Russian Federation
Irkutsk Regional Clinical Tuberculosis Hospital Recruiting
Irkutsk, Russian Federation
Contact: Oleg Ogarkov, PhD    obogarkov@gmail.com

Sponsors and Collaborators

University of Virginia
National Institute on Drug Abuse (NIDA)
Scientific Center for Family Health and Human Reproduction Problems, Russia

Investigators

Principal Investigator: Scott K Heysell University of Virginia
More Information

More Information


Responsible Party: Scott Heysell, MD, Associate Professor of Medicine, University of Virginia  
ClinicalTrials.gov Identifier: NCT03819374   History of Changes  
Other Study ID Numbers: 20451  
  R01DA044137  
Study First Received: January 17, 2019  
Last Updated: January 25, 2019  
Individual Participant Data    
Plan to Share IPD: No  

Studies a U.S. FDA-regulated Drug Product: No  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
Tuberculosis

ClinicalTrials.gov processed this data on June 01, 2020
This information is provided by ClinicalTrials.gov.