Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03819374 |
| Other study ID # |
20451 |
| Secondary ID |
R01DA044137 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 15, 2018 |
| Est. completion date |
April 30, 2021 |
Study information
| Verified date |
March 2022 |
| Source |
University of Virginia |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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
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.
