Real Time Assessment of Drug Craving, Use, and Abstinence During Outpatient: A Development and Feasibility Study

Background. We have already completed the original, major arm of this protocol (a
natural-history study of craving and lapse). Still open for enrollment is the second minor
arm (a within-subject trial of PDA-based treatment-task reminders). In the third arm there
will be enhanced assessment of mood, stress, and geographical location to further study
craving and lapse. All arms of the study have developed from either or both of two aspects of
the original arm: (1) Our growing appreciation of the technical possibilities of electronic
data collection in participants daily environments, and (2) our growing interest in having
participants provide descriptive data about the day-to-day experience of addiction and
recovery.

The major completed arm of the protocol has provided a wealth of descriptive data on drug
craving and lapse via Ecological Momentary Assessment (EMA), in which participants carry
handheld data-collection devices (electronic diaries, EDs) on which they report, in real
time, their activities and moods. Beyond data monitoring, EDs can be used to complement
behavioral interventions. The data-collection devices can be additionally programmed to
prompt completion of therapist-assigned homework exercises; by extending support outside the
therapy session, clinical outcome may be improved. Furthermore, there is an evidenced
association between completion of homework exercises and therapeutic outcome. Adapting
existing homework assignments to make them more engaging may increase homework completion
and, in turn, general compliance with therapy (Arm 2). The rationale for the third arm of the
study is to broaden the perspective of the examination of the natural history of drug
cravings and lapses by refining our assessments of geographical location and the stressors
associated with it. In doing so, we intend to investigate determinants of addiction that are
not reducible to individual-level traits but are instead reflective of broader socioeconomic
problems manifested in differences among neighborhoods.

Scientific goals. Arm 1) To investigate the relationships between putative triggers and drug
craving and lapse; Arm 2) To investigate interactive effects of electronic-diary reminders,
and simplified therapy-assigned homework tasks, on homework completion and therapeutic
outcome; Arm 3) Using refinements in our assessment methods, to investigate the role of
stress associated with geographical location in drug craving and use.

Participant population. Arm 2: 35 cocaine-abusing opioid-dependent outpatients. Arm 3: 50
cocaine-abusing opioid-dependent outpatients (separate from those in Arm 2). Target
enrollment for both arms will include 40% women and 60% minorities (mostly African-American).



Experimental design and methods. After 3 weeks of stabilization on daily methadone,
outpatients will undergo 25 weeks of EMA. EMA will consist of event-triggered recordings
(initiated by participants whenever they use heroin or cocaine, or whenever they feel an urge
to do so) and random-signal-triggered recordings (3 per day). Target quit dates for heroin
and cocaine will occur, respectively, on the first and third weeks of EMA. Two days after the
cocaine quit date, all participants will begin 12 weeks of intensive voucher-based
contingency management to reinforce abstinence from heroin and cocaine. Arm 2: During the
same 12 weeks, a within-subjects manipulation will occur: participants will receive
simplified versions of the current counselor-assigned homework tasks, and participants will
receive a daily reminder via the PDA to complete their homework tasks (whether they are
standard or simplified versions). The simplified homework tasks and reminders will be given
during two separate, counterbalanced, three-week blocks. Arm 3: Starting at week 4 and
continuing through week 18 participants will answer enhanced EMA questions regarding stress,
mood, location, drug craving and use. Additionally, participants in Arm 3 will carry GPS
units to record their locations during these 15 weeks. GPS location will be examined with
their drug use, craving and self-reported mood. They will also complete retrospective stress
questionnaires at week 3 and then at 4-week intervals throughout the completion of the study:
week 7, 11, 15, 19, 23, and 27. After the 12-week homework (Arm 2) or enhanced EMA phase (Arm
3) ends, participants will have the choice of transferring to a community clinic or
undergoing an eight-week taper from methadone. For participants in Arm 2 who choose to detox
at Archway, EMA may continue. However, for participants in Arm 3, no EMA or GPS data will be
collected during the pre-detox or detox phase (weeks 19-28).



Benefits to participants and/or society. Direct benefits to participants include
psychological and pharmacologic assistance for decreasing illicit drug use. The methadone
administered during the study will decrease the participants intravenous opiate use. The
contingency management and psychotherapy procedures may further reduce drug use and HIV risk
behaviors. The decrease in HIV risk behaviors should result in lower incidence of HIV
disease. Benefits to society include an increase in scientific understanding of the
precipitants and process of craving, lapse, and relapse, and an improvement in our ability to
assess the clinical effectiveness of relapse-prevention medications in future clinical
trials.



Risks to participants. Participants on methadone may experience side effects of sedation,
constipation, or mild euphoria. The risks of overmedication will be reduced by gradually
increasing the dose of methadone over the first week. The methadone dose used in Arm 2 of
this protocol, 100 mg, is within the limits allowed by the FDA guidelines and within the dose
range used in methadone clinics in Baltimore. For Arm 3 of the protocol, there is no ceiling
methadone dose. Methadone doses will be adjusted by the MRP as clinically indicated based on
participant feedback, withdrawal signs/symptoms, reported cravings, and urine toxicology
results. If a patient shows signs of intoxication, the MRP will reduce the methadone dose
until evidence of intoxication has subsided. Methadone will be discontinued if a participant
experiences severe side effects. Participants who are withdrawn from methadone will
experience opiate withdrawal symptoms, but these symptoms will be minimized by the long detox
period of 8 to 12 weeks. Other risks are the inconvenience of carrying and using the EDs, and
possible embarrassment from providing urine samples under observation, and concern about the
collection of GPS data.

- INCLUSION CRITERIA:

1. Age between 18 and 65;

2. Evidence of physical dependence on opioids (self-report and physical exam);

3. Evidence of cocaine and opiate use (self-report and urine screen).



EXCLUSION CRITERIA:

1. Schizophrenia or any other 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. Medical illness that in the view of the investigators would compromise participation
in research;

5. Urologic conditions that would inhibit urine collection;

6. In arm 2 only: current or recent maintenance on a methadone dose substantially higher
than the arm 2 ceiling dose of 100 mg/day; the MRP will evaluate this case by case.