Developing Field Tools for Real-Time Assessment of Exposure to Psychosocial Stress and Drug Use in an Outpatient Treatment Population

Background. This protocol arose in response to NIH s Genes and Environment Initiative (GEI).
There is no genetic component to this protocol (update: no genetics initially but added by
amendment in February 2013); rather, the goal is to develop field-deployable measures of
environmental influences (stressors, drug exposure, etc.) that can ultimately be used in
studies of gene-environment interactions.



Objective. To use Smartphones (PDAs) to measure stress and drug use; Global Positioning
System (GPS) units to assess geographical location; biological samples for genetic testing;
Daysimeters and Dimesimeters to assess circadian rhythm; AutoSense and Health Tag to collect
ambulatory physiological and activity data in real time; and to assess the feasibility and
acceptability of mobile HIV/STD Risk Reduction (HIVRR) or stress-reduction intervention with
feedback from Health Tag delivered via PDA in real time.

Participant population. Opioid-dependent outpatient adults (up to 500 enrolled; up to 400
completers). Target enrollment will include 40% women and 60% minorities (mostly
African-American).

Experimental design. A natural-history study of stress (both personal and environmental) and
drug use.

Methods. Participants will undergo 22 weeks of daily methadone or buprenorphine/naloxone
(henceforth buprenorphine ) maintenance and will be offered at least 8 weeks of methadone or
buprenorphine taper (weeks 23-30). To track drug use, stress, and geographical location (a
measure of environmental risk), each participant will carry a PDA and a GPS unit for 16 of
the first 18 weeks. Event-triggered entries will be initiated by participants (1) each time
that they use a drug and (2) each time they feel overwhelmed, anxious, or stressed more than
usual. Participants will also make 3 random-signal-triggered recordings per day and one brief
end of day recording. We will compare EMA results with more traditional assessments of drug
use and stress: (1) urine will be collected three times weekly during weeks 1-22 and once
weekly during the optional methadone or buprenorphine taper (weeks 23-30), (2) retrospective
self-report questionnaires on drug use and stress will be given regularly, and (3) laboratory
session examining responsiveness to a standardized stressor will occur during the 4th 6th
week. Blood draws and anthropometric measurements to assess allostatic load (a physiological
marker of long-term cumulative stress) and blood samples will be obtained for genetic
analysis during the 2nd 4th week. After week 12, we will also assess the impact of opioid
agonist treatment on the hypothalamic-pituitary-adrenal (HPA) axis which is involved in
modulating stress. After 18 weeks of opioid agonist maintenance, participants will begin an
additional 4 weeks of maintenance, during which they will not carry the PDA and GPS unit
unless they are participating in a secondary study that includes those measures. At the end
of 22 weeks, participants will have the choice of transferring to a community clinic or
undergoing an eight-week taper at the Archway clinic. Secondary studies: Up to 70
participants will be asked to wear the Daysimeter and an Actigraph activity-monitor
wristwatch for 18 days (two 72-hour intervals repeated three times) and the Dimesimeter daily
(24 hours/day) for 16 weeks. Up to 80 participants will be asked to wear the AutoSense for
four 1-week periods, including during laboratory sessions. Up to 40 participants will be
enrolled in the mHIVRR evaluation program for 4 weeks during the Maintenance Phase (completed
October 2013). Up to 100 participants will be asked to wear a SleepProfiler during 7 nights
to assess sleep architecture. Up to 50 participants will be asked to wear the Health Tag for
up to 6 weeks.

Primary outcome measures: (1) EMA reports of drug use and psychosocial stress, and (2)
real-time assessment of environmental risk exposure as measured via integration of GPS data
with the Neighborhood Psychosocial Index. Data for the methadone and buprenorphine groups
will be analyzed separately for the primary outcome measures and combined as appropriate.

Secondary outcome measures: To determine the feasibility and acceptability of using (1) the
Daysimeter/Dimesimeter and Actigraph to collect real-time field data on light exposure and
its impact on circadian rhythms, and (2) the Autosense to collect real-time field data on
physiological function. Also, to (3) combine Daysimeter/Dimesimeter data with
electronic-diary data to determine whether heroin/cocaine users experience circadian
disruption and, if so, how this disruption is related to psychosocial stress and illicit drug
use, (4) combine Autosense data with electronic-diary data to determine if physiological
responses to triggers can be used to inform drug relapse prevention efforts, (5) To determine
the feasibility and acceptability of interactive mHIVRR software programs to deliver
counseling and HIV education, and to determine whether they reduce HIV-related risk via
increased HIV/STD knowledge, (6) to determine if the HPA axis is normal after at least 3
months of opioid agonist treatment, (7) to incorporate genetic characteristics as predictors
of EMA and GMA data and other behavioral measures, (8) to assess how objectively measured
sleep quality is associated with EMA-reported psychosocial stress and reward responsiveness,
and with geographical exposure to stressful and rewarding environments, (9) to determine the
feasibility of using a more up-to-date EMA interface and device, and to examine the
relationship between opioid withdrawal symptoms and successful taper from methadone or
buprenorphine maintenance and (10) to obtain qualitative data on participants perceptions of
their environments, in order to inform future work and to help explain why participants seem
to do better in more disordered environments. (11) To evaluate the feasibility of using the
Spire Health Tag to infer emotional state from respiratory status, with the eventual goal
(not an aim in this protocol) of providing a just-in-time intervention to relieve stress and
anxiety.

- INCLUSION CRITERIA:

Participants will be eligible for inclusion in the study if they meet the following
criteria:

1. Age between 18 and 75

2. Physical dependence on opioids (by positive urine and/or frank opioid withdrawal)

3. Baltimore City or Baltimore, Harford, Howard, or Anne Arundel County home address or
report of working in Baltimore city or spending most of their waking hours in
Baltimore city.

EXCLUSION CRITERIA:

1. History of any DSM-IV psychotic disorder; history of bipolar disorder; current Major
Depressive Disorder

2. Current dependence on alcohol or sedative-hypnotic, e.g. benzodiazepine (by DSM-IV
criteria)

3. Cognitive impairment severe enough to preclude informed consent or valid self-report

4. Any condition that interferes with urine collection

5. Medical illness (e.g., cirrhosis, nephrotic syndrome, thyroid disease, ischemic heart
disease, epilepsy, panhypopituatarism, adrenal insufficiency, etc.) or medications
that, in the view of the investigators, would compromise participation in research
(e.g., glucocorticoids, adrenal extract supplements, spirnolactone, pregnenolone,
etc.)

Treatment Elsewhere (TE) Arm:

1. History of any DSM-IV psychotic disorder; history of bipolar disorder; current Major
Depressive Disorder;

2. cognitive impairment severe enough to preclude informed consent or valid self-report;

3. Any condition that interferes with urine collection.

Further Exclusions and Rescheduling Criteria for All Laboratory Sessions:

1. The self-reported use of over-the-counter or as needed medications (e.g., antacids,
sleeping aids, antihistamines, etc.) for 5 days prior to the scheduled session

2. Positive breathalyzer test (BAL > 0) and/or acute intoxication from illicit drugs or
alcohol

3. Positive pregnancy test

4. Self-report of recent pregnancy or child birth (and no resumption of normal menses)

5. Failure to fast.

Participants will be allowed to reschedule 1 time (in total, for all 3 sessions):

Other reasons for which participants may be rescheduled:

- They report significant recent health (e.g. influenza, infection, wound) or emotional
(e.g. death in the family) events.

- Are late for session

Further Inclusion/Exclusion for the HPA axis component:

Inclusion

- Receiving buprenorphine agonist therapy (dose range 16-24 mg)

- Stable buprenorphine dose for 30 days prior

Exclusions (based on impact on HPA axis and neuroendocrine function)

- HIVpositive

- Pregnancy