Developing Adaptive Interventions for Cocaine Cessation and Relapse Prevention

Drug addiction is a chronic, devastating, but treatable disorder, for which there exists a
growing armamentarium of evidence-based interventions, including pharmacotherapies and
psychotherapies. A core principle of drug addiction treatment, however, states that no single
treatment is appropriate for everyone; rather, treatments need to be adjusted based on
patient characteristics and response in order to be maximally effective. Ideally, clinicians
would identify a sequence of interventions that works best across different stages of
addiction treatment, from abstinence initiation to relapse prevention. Adaptive treatment
interventions have been used successfully to inform this sequential clinical decision-making
process. For cocaine use disorders (CUD), the most potent intervention currently available
for initiating abstinence is behavior therapy using contingency management (CM) procedures.
Intensive CM has been shown to produce initial cocaine abstinence rates of 40%, unmatched by
all other forms of behavioral or pharmacological treatment, making it a prototypical
first-line therapy for CUD. Importantly, achievement of initial abstinence predicts future
abstinence. For the clinician, these research findings translate into a straightforward
question: Can the investigators drive CM response rates even higher with targeted adjunctive
interventions?

The proposed sequential, multiple assignment, randomized trial (SMART) will provide the data
needed to answer this question. First, the investigators will determine whether Acceptance
and Commitment Therapy (ACT) in combination with CM increases initial treatment response
rates. The investigators hypothesize that four weeks of treatment with ACT+CM will produce
higher abstinence rates than initial treatment combining standard Drug Counseling with CM
(DC+CM). The hypothesized synergism of ACT+CM on primary treatment mechanisms of experiential
avoidance and reward sensitivity, respectively, will be examined. Second, for patients who do
not respond to initial treatment, the investigators will examine whether dopamine-targeted
pharmacotherapy is an effective augmentation strategy. Specifically, the investigators
hypothesize that continued ACT+CM treatment with modafinil augmentation will be most
effective in promoting abstinence relative to treatment combinations involving continued DC
and/or placebo. Third, for patients who respond to initial treatment, the investigators will
assess the relative benefit of continued treatment with ACT+CM, as compared to DC+CM, to
prevent relapse. ACT emphasizes goal-directed actions based on values that are intrinsically
motivating, and is thereby expected to be a more effective intervention for extending the
duration of abstinence following initial treatment with intensive CM.

Inclusion Criteria:

1. be between 18 and 60 years of age

2. meet DSM-5 criteria for current cocaine use disorder of at least moderate severity (≥
4 symptoms)

3. have at least 1 positive urine BE specimen (≥ 150 ng/mL) during intake

4. be in acceptable health on the basis of interview, medical history and physical exam

5. agree to use an acceptable method of birth control during study participation and for
one month after discontinuation of the study medication. Non-hormonal methods of
contraception are recommended, including barrier contraceptives (e.g., diaphragm,
cervical cap, male condom) or intrauterine device (IUD). Steroid contraceptives if
used with non-hormonal methods are acceptable.

6. be able to understand the consent form and provide written informed consent

7. be able to provide the names of at least 2 persons who can generally locate their
whereabouts.

Exclusion Criteria:

1. current DSM-5 diagnosis for substance use disorder (of at least moderate severity)
other than cocaine, marijuana, or nicotine

2. have a DSM-5 axis I psychiatric disorder or neurological disease or disorder requiring
ongoing treatment and/or making study participation unsafe (e.g., psychosis,
dementia).

3. significant current suicidal or homicidal ideation

4. medical conditions contraindicating modafinil pharmacotherapy (e.g., major
cardiovascular disease, severe liver disease based on Child-Pugh score of B or C,
serious kidney problems)

5. taking medications that could adversely interact with modafinil (e.g., propranolol,
phenytoin, warfarin, diazepam)

6. having conditions of probation or parole requiring reports of drug use to officers of
the court

7. impending incarceration

8. pregnant or nursing for female patients

9. inability to read, write, or speak English