Effectiveness of Modafinil and D-amphetamine in Treating Cocaine Dependent Individuals

Study Overview
=================
Brief Summary
-----------------
Cocaine dependence is a major public health problem; an effective primary treatment for cocaine dependent individuals has yet to be found. The purpose of this study is to examine the effects of d-amphetamine and modafinil, when given alone and in combination, in treating cocaine dependent individuals.

Detailed Description
-----------------
Cocaine is a strong central nervous system stimulant that is widely abused throughout the United Sates. Due to its widespread use, it is important to develop an effective treatment for cocaine dependence. Modafinil is a glutamate-enhancing agent. D-amphetamine is a central nervous system stimulant that is approved to treat individuals with narcolepsy and attention deficit disorder. Both modafinil and d-amphetamine may be effective treatments for cocaine dependence. The purpose of this study is to examine the effectiveness of modafinil and d-amphetamine, alone and in combination, in treating cocaine dependent individuals. This study will last 16 weeks. Participants will be randomly assigned to one of four groups: 1) 60 mg dose of d-amphetamine; 2) 400 mg dose of modafinil; 3) 30 mg dose of d-amphetamine combined with 200 mg dose of modafinil; and 4) placebo. All participants will receive 200 mg of modafinil over 4 days.

Official Title
-----------------
Pharmacotherapy Dosing Regimen (Cocaine Dependence Population)

Conditions
-----------------
Cocaine-Related Disorders

Intervention / Treatment
-----------------
* Drug: D-Amphetamine 30mg
* Drug: D-Amphetamine 60mg
* Drug: Modafinil 200mg
* Drug: Modafinil 400mg
* Behavioral: Therapy
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meets Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV (SCID) criteria for cocaine abuse or dependence In general good health. Individuals who are HIV-positive will not be excluded if in good general health, unless medication interactions exist. Exclusion Criteria: Meets diagnostic criteria for psychiatric disorders, including other forms of drug dependence, other than nicotine Current cardiovascular disease, as determined by an electrocardiogram On probation or parole if the circumstances do not allow study completion or if ethical constraints of supervision do not allow confidentiality Previously received treatment with d-amphetamine, modafinil, or aripiprazole Currently receiving prescribed medication

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D-Amphetamine 60mg + Therapy<br>During the 16 weeks of outpatient treatment, participants took three capsules daily (two in the morning, one in the afternoon). All active and placebo capsules were identical in appearance and each contained 50mg riboflavin for subsequent evaluation of medication compliance. Medication administration was initiated during a 5 day run-up period. d-Amphetamine sustained release (SR) (Dexedrine Spansules) started at 15 mg (day 1-2), increased to 30mg (day3; 15mg, BID), 45mg (day4; 15mg, TID), and 60mg (day5; 15mg bid plus 30mg qd). A 5-day dose reduction schedule occurred at week 17. Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills. | Drug: D-Amphetamine 60mg<br> <br> Behavioral: Therapy<br>* Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills.<br>|
| Experimental: Modafinil 400mg + Therapy<br>During the 16 weeks of outpatient treatment, participants took three capsules daily (two in the morning, one in the afternoon). All active and placebo capsules were identical in appearance and each contained 50mg riboflavin for subsequent evaluation of medication compliance. Medication administration was initiated during a 5 day run-up period. Modafinil started at 200mg (day1) and increased to 400mg (days2-5). A 5-day dose reduction schedule occurred at week 17. Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills. | Drug: Modafinil 400mg<br> <br> Behavioral: Therapy<br>* Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills.<br>|
| Experimental: Modafinil 200mg + D-Amphetamine 30mg + Therapy<br>During the 16 weeks of outpatient treatment, participants took three capsules daily (two in the morning, one in the afternoon). All active and placebo capsules were identical in appearance and each contained 50mg riboflavin for subsequent evaluation of medication compliance. Medication administration was initiated during a 5 day run-up period. For the combination condition, dosages of modafinil and d-amphetamine were escalated to one-half of that for the single medication conditions. A 5-day dose reduction schedule occurred at week 17. Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills. | Drug: D-Amphetamine 30mg<br> <br> Drug: Modafinil 200mg<br> <br> Behavioral: Therapy<br>* Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills.<br>|
| Placebo Comparator: Placebo + Therapy<br>During the 16 weeks of outpatient treatment, participants took three capsules daily (two in the morning, one in the afternoon). All active and placebo capsules were identical in appearance and each contained 50mg riboflavin for subsequent evaluation of medication compliance. Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills. | Behavioral: Therapy<br>* Manual-based, cognitive-behavioral therapy was provided for 1 hour each week by master's-level therapists. The cognitive-behavioral therapy emphasized relapse prevention and coping skills.<br>Drug: Placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cocaine Use as Assessed by the Treatment Effectiveness Score (TES), Which is the Total Number of Cocaine-negative Urines During Treatment |  | 16 weeks | 
| Retention as Indicated by the Number of Participants Who Completed 16 Weeks of Treatment |  | 16 weeks | 
| Retention as Indicated by the Number of Participants Who Remained in the Study |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication Compliance as Indicated by Percentage of Pills Taken According to Self-report |  | 16 weeks | 
| Medication Compliance as Indicated by Percentage of Riboflavin-positive Urine Samples |  | 16 weeks |