Developing Adaptive Interventions for Cocaine Cessation and Relapse Prevention

Study Overview
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Brief Summary
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First, the investigators will determine whether Acceptance and Commitment Therapy in combination with Contingency Management increases initial treatment response rates. Second, for patients who do not respond to initial treatment, the investigators will examine whether dopamine-targeted pharmacotherapy is an effective augmentation strategy. Third, for patients who respond to initial treatment, the investigators will assess the relative benefit of continued treatment with Acceptance and Commitment Therapy in combination with Contingency Management, as compared to Drug Counseling in combination with Contingency Management, to prevent relapse.

Detailed Description
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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.

Official Title
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Developing Adaptive Interventions for Cocaine Cessation and Relapse Prevention (Adaptive Trial)

Conditions
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Cocaine-Related Disorders

Intervention / Treatment
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* Behavioral: Acceptance and Commitment Therapy (ACT)
* Behavioral: Drug Counseling (DC)
* Behavioral: Contingency Management (CM)
* Drug: Placebo
* Drug: Modafinil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: be between 18 and 60 years of age meet DSM-5 criteria for current cocaine use disorder of at least moderate severity (≥ 4 symptoms) have at least 1 positive urine BE specimen (≥ 150 ng/mL) during intake be in acceptable health on the basis of interview, medical history and physical exam 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. be able to understand the consent form and provide written informed consent be able to provide the names of at least 2 persons who can generally locate their whereabouts. Exclusion Criteria: current DSM-5 diagnosis for substance use disorder (of at least moderate severity) other than cocaine, marijuana, or nicotine 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). significant current suicidal or homicidal ideation 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) taking medications that could adversely interact with modafinil (e.g., propranolol, phenytoin, warfarin, diazepam) having conditions of probation or parole requiring reports of drug use to officers of the court impending incarceration pregnant or nursing for female patients inability to read, write, or speak English

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACT plus CM<br>Acceptance and Commitment Therapy along with Contingency Management for cocaine use will be administered to help decrease experiential avoidance while increasing acceptance and willingness to experience unpleasant thoughts, feelings, and physical symptoms. | Behavioral: Acceptance and Commitment Therapy (ACT)<br>* ACT will assist cocaine patients to notice internal cravings and triggers, abandon attempts to manage these triggers via active avoidance, suppression or other control-based strategies, and to make commitments to engage in behaviors consistent with chosen values or goals. ACT encourages clients to experience thoughts and feelings from an observer perspective, and helps clients not to believe distressing thoughts and feelings as if those thoughts and feelings are literally true and in need of action. ACT treatment will be based on the ACT therapy manual developed and tested previously.<br>* Other names: ACT;Behavioral: Contingency Management (CM)<br>* The investigators will use the same high-magnitude CM schedule shown previously to be feasible and effective in facilitating initial cocaine abstinence. Subjects will earn vouchers for cocaine-negative urine samples collected at scheduled clinic visits each week. Under an escalating reinforcement schedule, voucher values will begin at $15 and increase by $10 for each consecutive negative urine. Bonus vouchers of $10 will be given for three consecutive negative urines. Provision of a cocaine-positive urine or failure to provide a scheduled sample will result in no vouchers earned and will reset the schedule to the initial value of $15.<br>* Other names: CM;|
| Active Comparator: ACT plus CM, with Placebo<br>Acceptance and Commitment Therapy along with Contingency Management for cocaine use will be administered and augmented with a placebo capsule during Phase 2 (weeks 5-12). | Behavioral: Acceptance and Commitment Therapy (ACT)<br>* ACT will assist cocaine patients to notice internal cravings and triggers, abandon attempts to manage these triggers via active avoidance, suppression or other control-based strategies, and to make commitments to engage in behaviors consistent with chosen values or goals. ACT encourages clients to experience thoughts and feelings from an observer perspective, and helps clients not to believe distressing thoughts and feelings as if those thoughts and feelings are literally true and in need of action. ACT treatment will be based on the ACT therapy manual developed and tested previously.<br>* Other names: ACT;Behavioral: Contingency Management (CM)<br>* The investigators will use the same high-magnitude CM schedule shown previously to be feasible and effective in facilitating initial cocaine abstinence. Subjects will earn vouchers for cocaine-negative urine samples collected at scheduled clinic visits each week. Under an escalating reinforcement schedule, voucher values will begin at $15 and increase by $10 for each consecutive negative urine. Bonus vouchers of $10 will be given for three consecutive negative urines. Provision of a cocaine-positive urine or failure to provide a scheduled sample will result in no vouchers earned and will reset the schedule to the initial value of $15.<br>* Other names: CM;Drug: Placebo<br>* The placebo capsule will be filled with corn starch and riboflavin.<br>* Other names: Corn Starch;|
| Experimental: ACT plus CM, with Modafinil<br>Acceptance and Commitment Therapy along with Contingency Management for cocaine use will be administered and augmented with a Modafinil (300mg) capsule during Phase 2 (weeks 5-12). | Behavioral: Acceptance and Commitment Therapy (ACT)<br>* ACT will assist cocaine patients to notice internal cravings and triggers, abandon attempts to manage these triggers via active avoidance, suppression or other control-based strategies, and to make commitments to engage in behaviors consistent with chosen values or goals. ACT encourages clients to experience thoughts and feelings from an observer perspective, and helps clients not to believe distressing thoughts and feelings as if those thoughts and feelings are literally true and in need of action. ACT treatment will be based on the ACT therapy manual developed and tested previously.<br>* Other names: ACT;Behavioral: Contingency Management (CM)<br>* The investigators will use the same high-magnitude CM schedule shown previously to be feasible and effective in facilitating initial cocaine abstinence. Subjects will earn vouchers for cocaine-negative urine samples collected at scheduled clinic visits each week. Under an escalating reinforcement schedule, voucher values will begin at $15 and increase by $10 for each consecutive negative urine. Bonus vouchers of $10 will be given for three consecutive negative urines. Provision of a cocaine-positive urine or failure to provide a scheduled sample will result in no vouchers earned and will reset the schedule to the initial value of $15.<br>* Other names: CM;Drug: Modafinil<br>* Modafinil capsules will start at 200 mg (day 1) and increase to the fixed dose of 300 mg (day 2) and will also contain riboflavin.<br>* Other names: Provigil;|
| Active Comparator: DC plus CM<br>Drug Counseling and Contingency Management for cocaine use will be administered to help educate patients about important concepts in addiction recovery. | Behavioral: Drug Counseling (DC)<br>* The investigators will use the manual-guided individual DC modeled after the NIDA Collaborative Cocaine Treatment Study and used as the active control therapy in previous studies. DC approximates clinical practice as it is considered the most common type of evidence-based treatment in the community for patients actively using cocaine.<br>* Other names: DC;Behavioral: Contingency Management (CM)<br>* The investigators will use the same high-magnitude CM schedule shown previously to be feasible and effective in facilitating initial cocaine abstinence. Subjects will earn vouchers for cocaine-negative urine samples collected at scheduled clinic visits each week. Under an escalating reinforcement schedule, voucher values will begin at $15 and increase by $10 for each consecutive negative urine. Bonus vouchers of $10 will be given for three consecutive negative urines. Provision of a cocaine-positive urine or failure to provide a scheduled sample will result in no vouchers earned and will reset the schedule to the initial value of $15.<br>* Other names: CM;|
| Active Comparator: DC plus CM, with Placebo<br>Drug Counseling and Contingency Management for cocaine use will be administered and augmented with a placebo capsule during Phase 2 (weeks 5-12). | Behavioral: Drug Counseling (DC)<br>* The investigators will use the manual-guided individual DC modeled after the NIDA Collaborative Cocaine Treatment Study and used as the active control therapy in previous studies. DC approximates clinical practice as it is considered the most common type of evidence-based treatment in the community for patients actively using cocaine.<br>* Other names: DC;Behavioral: Contingency Management (CM)<br>* The investigators will use the same high-magnitude CM schedule shown previously to be feasible and effective in facilitating initial cocaine abstinence. Subjects will earn vouchers for cocaine-negative urine samples collected at scheduled clinic visits each week. Under an escalating reinforcement schedule, voucher values will begin at $15 and increase by $10 for each consecutive negative urine. Bonus vouchers of $10 will be given for three consecutive negative urines. Provision of a cocaine-positive urine or failure to provide a scheduled sample will result in no vouchers earned and will reset the schedule to the initial value of $15.<br>* Other names: CM;Drug: Placebo<br>* The placebo capsule will be filled with corn starch and riboflavin.<br>* Other names: Corn Starch;|
| Experimental: DC plus CM, with Modafinil<br>Drug Counseling and Contingency Management for cocaine use will be administered and augmented with a Modafinil (300mg) capsule during Phase 2 (weeks 5-12). | Behavioral: Drug Counseling (DC)<br>* The investigators will use the manual-guided individual DC modeled after the NIDA Collaborative Cocaine Treatment Study and used as the active control therapy in previous studies. DC approximates clinical practice as it is considered the most common type of evidence-based treatment in the community for patients actively using cocaine.<br>* Other names: DC;Behavioral: Contingency Management (CM)<br>* The investigators will use the same high-magnitude CM schedule shown previously to be feasible and effective in facilitating initial cocaine abstinence. Subjects will earn vouchers for cocaine-negative urine samples collected at scheduled clinic visits each week. Under an escalating reinforcement schedule, voucher values will begin at $15 and increase by $10 for each consecutive negative urine. Bonus vouchers of $10 will be given for three consecutive negative urines. Provision of a cocaine-positive urine or failure to provide a scheduled sample will result in no vouchers earned and will reset the schedule to the initial value of $15.<br>* Other names: CM;Drug: Modafinil<br>* Modafinil capsules will start at 200 mg (day 1) and increase to the fixed dose of 300 mg (day 2) and will also contain riboflavin.<br>* Other names: Provigil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cocaine Use as Assessed by Proportion of Visits (Excluding Excused Absences) With Cocaine-negative Urine Drug Screen | Urine is assessed for levels of the cocaine metabolite benzoylecgonine (BE), and the drug screen is considered positive for cocaine use if BE level is ≥ 150 ng/mL. | 4 weeks | 
| Cocaine Use as Assessed by Proportion of Visits (Excluding Excused Absences) With Cocaine-negative Urine Drug Screen | Urine is assessed for levels of the cocaine metabolite benzoylecgonine (BE), and the drug screen is considered positive for cocaine use if BE level is ≥ 150 ng/mL. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cocaine Use as Indicated by Proportion of Days of no Cocaine Use as Assessed by Timeline Follow-back | Timeline Followback (TLFB) is a method to assess of cocaine use that involves asking study participants to self-report their cocaine use over the past week. | 4 weeks | 
| Cocaine Use as Assessed by Proportion of Days of no Cocaine Use as Assessed by Timeline Follow-back | Timeline Followback (TLFB) is a method to assess of cocaine use that involves asking study participants to self-report their cocaine use over the past week. | 12 Weeks |