Modafinil and Naltrexone to Reduce Cocaine and Alcohol Dependence

Cocaine and alcohol addiction are serious health problems with no available medical treatment
for preventing relapse. Past research has shown that individuals who are addicted to both
cocaine and alcohol typically respond poorly to conventional substance abuse treatment.
Little attention has been directed towards how best to treat these individuals. Naltrexone is
a medication that is currently used to treat drug and alcohol addiction. It acts by blocking
the "high" feeling produced by drugs and alcohol. Modafinil, another medication, enhances
mood, increases energy, and improves concentration in people with narcolepsy. Preliminary
research has shown that it may produce similar effects to cocaine, thereby potentially
countering the symptoms of cocaine withdrawal. Cognitive Behavioral Coping Skills Therapy
(CBT), a form of therapy that aims to alter an individual's patterns of behavior and drug
use, is also an important component of substance abuse treatment. The purpose of this study
is to compare the effectiveness of CBT plus placebo, CBT plus modafinil, CBT plus naltrexone,
and CBT plus a combination of modafinil and naltrexone at reducing cocaine and alcohol use in
individuals addicted to both substances.

This 14-week study will enroll individuals addicted to both cocaine and alcohol. During a
1-week screening period, potential participants will be required to complete a detoxification
program, including stopping all cocaine and alcohol use. Participants will also undergo a
physical exam and an electrocardiogram. Blood will be drawn for laboratory tests, and urine
tests will be used to screen for the presence of drugs and alcohol. Individuals who complete
the screening and meet all study requirements will be permitted to participate in the
treatment phase of the study. During the 13-week treatment phase, participants will be
randomly assigned to receive modafinil, naltrexone, a combination of modafinil and
naltrexone, or placebo. All participants will attend a CBT session once a week. Study visits
will take place twice a week. At each visit, a urine test and breathalyzer will be used to
screen for the presence of alcohol and drugs. Participants will also complete standardized
psychological questionnaires to measure drug and alcohol craving, treatment services
received, severity of illness, and withdrawal symptoms. In addition, participants will meet
weekly with a nurse practitioner, who will dispense study medications, monitor adverse
events, and evaluate the participant's clinical status. A follow-up evaluation will occur 6
months following the end of treatment.

4.1 Inclusion Criteria

1. Male and females, 18 years of age or older.

2. Meets DSM-IV criteria for current diagnoses of cocaine and alcohol dependence,
determined by the SCID-IV.

3. In the past 30 days, used no less than $200-worth of cocaine and meets the following
drinking criteria as measured by the Timeline Followback (TLFB) (Sobell, 1995):

1. drank within 30 days of intake day,

2. reports a minimum of 48 standard alcoholic (avg. 12 drinks/wk) in a consecutive
30-day period over the 90-day period prior to starting intake (i.e., a minimum of
40% days drinking), and

3. has 2 or more days of heavy drinking (defined as 5 or more drinks per day in
males and 4 or more drinks per day in females) in this same pre-treatment period.

4. 72 consecutive hours of abstinence from alcohol, determined by self-reports and
confirmed by a negative breathalyzer tests, and a Clinical Institute Withdrawal Scale
for Alcohol (CIWA-AR) (Sullivan, 1989) score below eight. Subjects will be encouraged
to achieve 72 consecutive hours of abstinence, however, subjects who have achieved
between 48 and 72 consecutive hours of abstinence will be included with the approval
of the principal investigator. We anticipate that these subjects will comprise less
than 5% of total enrolled subjects. Subjects will be given 2 additional weeks beyond
the screening week to attain the appropriate period of alcohol abstinence prior to
randomization.

5. Lives a commutable distance from the TRC and agrees to attend all research visits
including follow-up visits.

6. Speaks, understands, and prints in English

7. Ability to give informed consent

Exclusion Criteria

1. Abstinent from cocaine or alcohol for 30 consecutive days prior to signing consent
form.

2. Meets DSM IV criteria for dependence on any substance other than cocaine and alcohol
(except nicotine), determined by the SCID.

3. Needs treatment with any psychoactive medications including any anti-seizure
medications (with the exception of diphenhydramine used sparingly, if necessary, for
sleep).

4. Meets current or lifetime DSM-IV criteria for schizophrenia or any psychotic disorder
or organic mental disorder. Subject meets current DSM-IV diagnosis of any other
clinically significant psychiatric disorder that will interfere with study
participation.

5. Has evidence of a history of significant hematological, pulmonary, endocrine,
cardiovascular, renal or gastrointestinal disease (including a history of myocardial
infarction, mitral valve prolapse, left ventricular hypertrophy, uncontrolled
hypertension).

6. Severe physical or medical illnesses such as AIDS, active hepatitis, significant
hepatocellular injury as evidenced by elevated total bilirubin levels (>1.3 mg/dl),or
elevated levels (over 4.5x normal) of aspartate aminotransferase (AST), and serum
glutamic-pyruvic transaminase (SGPT) after the required 3 days of abstinence.

7. Use of an investigational medication in the 30 days prior to randomization.

8. History of hypersensitivity to modafinil or naltrexone

9. Receiving chronic therapy with any drug known to interact adversely with either
modafinil or naltrexone including propranolol, phenytoin, warfarin, diazepam

10. Took a monoamine oxidase inhibitor within 30 days of randomization.

11. Is female and tests positive on a pregnancy test, is contemplating pregnancy in the
next 6 months, is nursing, or is not using an effective contraceptive method (if
relevant). Acceptable methods of contraception include barrier methods (diaphragm or
condom with spermicide, female condom), intrauterine progesterone contraceptive
system, levonorgrestrel implant, and medroxyprogeterone acetate contraceptive
injection, copper IUD, vaginal contraceptive film, cervical cap, contraceptive foam.

12. Current use of an oral contraceptive without other acceptable barrier method of
contraception.

13. Received therapy with any opiate substitute (methadone, LAAM, buprenorphine) within 60
days of randomization