A Sequenced Behavioral and Medication Intervention for Cocaine Dependence

Study Overview
=================
Brief Summary
-----------------
This study will investigate a treatment strategy in which a computer-assisted behavioral intervention will be used to help individuals stop their use of cocaine. A medication will be combined with the behavioral treatment among those individuals who do not respond to the behavioral intervention alone. The primary hypothesis of the study is that among cocaine dependent individuals who fail to respond to an initial trial of behavioral therapy, a greater proportion of individuals will benefit from the combined treatment (behavior therapy plus medication) compared to individuals in the comparison group.

Detailed Description
-----------------
Cocaine Dependence is associated with substantial social, physical, and neurobiological problems. Psychosocial treatments can be helpful for many individuals. However, a significant proportion of individuals do not benefit from counseling alone. Our research group has demonstrated that deficient dopamine transmission, predicts poor response to a behavioral treatment and that a regiment that included an agonist replacement strategy with stimulants maybe effective for promoting abstinence in severe cocaine dependent patients. In this 15-week study 145 treatment-seeking cocaine dependent participants will receive a computer-assisted behavioral intervention based on the community reinforcement approach with contingency management (CRA + CM). The counseling approach will include both computer-assisted life skills training via and counseling. Individuals who fail to achieve abstinence will continue the behavioral treatment (CRA + CM) and will be randomly assigned to a behavioral therapy enhancement strategy that will include either Mixed Amphetamine Salts-Extended Release (80mg) or placebo.

Official Title
-----------------
A Sequenced Behavioral and Medication Intervention for Cocaine Dependence

Conditions
-----------------
Cocaine Dependence

Intervention / Treatment
-----------------
* Behavioral: Computer-assisted behavior therapy
* Drug: Mixed-Amphetamine Salts- Extended Release (MAS-ER)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meets DSM-V criteria for cocaine use disorder. Used cocaine at least four days in the past month. Age 18-60. Able to give informed consent and comply with study procedures Exclusion Criteria: Meets DSM-V criteria for bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to drug abuse. Participants with MDD, with symptom severity that exceeds a HAM-D score of 20, and/or any other current Axis I psychiatric disorder as defined by DSM-V supported by the MINI that in the investigator's judgment are unstable, would be disrupted by study medication, or are likely to require specialized pharmacotherapy or psychotherapy during the study period. History of seizures, unexplained loss of consciousness, or traumatic brain injury. History of allergic reaction to candidate medication (amphetamine). Significant current suicidal risk. Pregnancy, lactation, or failure in sexually active female patients to use adequate contraceptive methods. Unstable physical disorders which might make participation hazardous such as uncontrolled hypertension, acute hepatitis, uncontrolled diabetes. Elevated transaminase levels (> 3x the normal limit). Coronary vascular disease History of failure to respond to a previous adequate trial of the candidate medication. Current physiological dependence on any other substance other than nicotine or cannabis that would require a medically supervised detoxification. Currently being prescribed psychotropic medication by another physician. Are legally mandated (e.g. to avoid incarceration, monetary or other penalties, etc.) to participate in substance abuse treatment program. Body Mass Index (BMI) < 18kg/m2. (amphetamine may produce weigh loss thus a minimum BMI cut-off is being used for study inclusion).

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Following an initial 4 week period where participants received computer-assisted behavioral intervention based on the community reinforcement approach with contingency management (CRA + CM), individuals who failed to achieve abstinence will continue the behavioral treatment (CRA + CM) and will be randomly assigned, in parallel, to a behavioral therapy enhancement strategy that will include either Mixed Amphetamine Salts-Extended Release (80mg) or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Computer-assisted CBT plus Mixed-Amphetamine Salts- Extended Release (MAS-ER)<br>Patients who are randomized to the computer-assisted behavior therapy plus mixed amphetamine salts (extended release) arm will have their dose titrated to 80 mg or the maximum tolerated extended release mixed amphetamine salts daily. Participants will be asked to take the medication once per day in the morning or early afternoon and will be maintained on this schedule through week 14 of the trial. Computer-assisted behavior therapy based on the Community Reinforcement Approach (CRA) to treating cocaine dependence. CRA is skills based treatment program that incorporates coping skills development and contingency management. Participants will attend the clinic 3x per week and receive counseling 2x per week. | Behavioral: Computer-assisted behavior therapy<br>* TES is a computer-assisted therapy program delivered via effective informational and multimedia technologies, includes 32 core interactive, multimedia modules, beginning with basic cognitive behavioral relapse prevention skills (e.g. drug refusal skills) and moving on to improving psychosocial functioning, (e.g. employment status, social relations) and HIV risk reduction.<br>* Other names: Therapeutic Educational System (TES);Drug: Mixed-Amphetamine Salts- Extended Release (MAS-ER)<br>* 80 mg/day of Mixed-Amphetamine Salts- Extended Release (MAS-ER) and computer -assisted CBT<br>* Other names: Adderall XR;|
| Placebo Comparator: Computer-assisted CBT plus placebo<br>Patients who are randomized to the Computer-assisted CBT plus placebo arm will have their medication dose titrated in a fix-flexible dose schedule matching the active medication arm. Participants will be asked to take the medication once per day in the morning or early afternoon and will be maintained on this schedule through week 14 of the trial. Computer-assisted behavior therapy based on the Community Reinforcement Approach (CRA) to treating cocaine dependence. CRA is skills based treatment program that incorporates coping skills development and contingency management. Participants will attend the clinic 3x per week and receive counseling 2x per week. | Behavioral: Computer-assisted behavior therapy<br>* TES is a computer-assisted therapy program delivered via effective informational and multimedia technologies, includes 32 core interactive, multimedia modules, beginning with basic cognitive behavioral relapse prevention skills (e.g. drug refusal skills) and moving on to improving psychosocial functioning, (e.g. employment status, social relations) and HIV risk reduction.<br>* Other names: Therapeutic Educational System (TES);Drug: Placebo<br>* Will receive computer -assisted CBT and placebo (instead of active Adderall-XR)<br>* Other names: Computer-assisted CBT, TES;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Those Achieving Three Consecutive Weeks of Cocaine Abstinence at the End of the Trial. | The primary outcome measure will be a binary indicator (yes or no) of at least 3 consecutive weeks of urine toxicology confirmed self-reported abstinence during the last three weeks of the trial. | weeks 12-14 of trial | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cocaine Dependence Treatment, Computer-assisted therapy, Pharmacotherapy