Modafinil and Naltrexone to Reduce Cocaine and Alcohol Dependence

Condition(s) targeted: Alcohol-Related Disorders; Alcoholism; Cocaine-Related Disorders

Intervention: Naltrexone (Drug); Modafinil (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute on Drug Abuse (NIDA)

Official(s) and/or principal investigator(s):
Helen M. Pettinati, PhD, Principal Investigator, Affiliation: University of Pennsylvania

Overall contact:
Donna Simpson, Phone: 215-243-9959

Modafinil is a medication that may enhance mood and increase energy in cocaine addicts, which may be useful in preventing cocaine relapse. Naltrexone is a medication that is currently used to treat drug and alcohol addiction. A combination of these two medications may be beneficial in reducing drug and alcohol use in individuals undergoing substance abuse treatment. The purpose of this study is to evaluate the effectiveness of modafinil and naltrexone, alone and in combination, at reducing drug and alcohol use in individuals addicted to cocaine and alcohol.

Official title: A Phase II, Double-Blind, Placebo-Controlled, Pilot Trial of the Combination of Modafinil and Naltrexone for the Treatment of Cocaine and Alcohol Dependence

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Cocaine use (measured by Timeline Follow Back and urine screen at Week 14 and the 6-month evaluation)

Number of days of abstinence from drinking and number of days of clinically significant drinking (measured by Timeline Follow Back at Week 14 and the 6-month evaluation)

Secondary outcome:

Naltrexone-treated subjects will demonstrate a significantly greater reduction in cocaine use measured by the number of BE-negative urine samples and significantly reduced alcohol use measured by fewer days of clinically significant drinking.

Modafinil-treated subjects will demonstrate a significantly greater reduction in cocaine use measured by the number of BE-negative urine samples and significantly reduced alcohol use measured by fewer days of clinically significant drinking.

Naltrexone/modafinil-treated subjects will have fewer days of cocaine use, more abstinent days from alcohol, and fewer heavy drinking days during the follow up period compared to placebo-treated subjects.

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Meets DSM-IV diagnostic criteria for cocaine and alcohol dependence, as determined by

the Structured Clinical Interview (SCID)

- Has used no less than $200 worth of cocaine in the 30 days prior to study entry

- Has used alcohol within 30 days of study entry, as measured by the Timeline Follow

Back

- Has consumed a minimum of 48 standard alcoholic drinks (average of 12 drinks per week)

in a consecutive 30-day period over the 90-day period prior to study entry (i. e., a minimum of 40% days drinking), as measured by the Timeline Follow Back

- 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 a consecutive 30-day period over the 90-day period prior to study entry, as measured by the Timeline Follow Back

- Has 5 consecutive days of abstinence from cocaine and alcohol, as determined by

self-report and confirmed by a negative urine screen, a negative breathalyzer test, a collateral report, and a score of less than 8 on the Clinical Institute Withdrawal Scale for Alcohol

- Lives within commuting distance of the treatment research clinic

- Agrees to attend all research visits, including follow-up visits

- Speaks, understands, and writes English

- If female, willing to use a non-oral form of contraception throughout the study

Exclusion Criteria:

- Meets DSM-IV diagnostic criteria for dependence on any substance other than cocaine,

alcohol, or nicotine, as determined by the SCID

- Has abstained from cocaine or alcohol for 30 consecutive days prior to study entry

- Has a positive urine drug screen for any drug other than cocaine in the week prior to

study entry (one repeat test is permitted)

- Meets DSM-IV diagnostic criteria for any of the following current Axis I disorders:

panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, or eating disorders

- Meets current or lifetime DSM-IV diagnostic criteria for schizophrenia, any psychotic

disorder, or organic mental disorder

- History of significant blood, lung, endocrine, heart, kidney, or gastrointestinal

disease (including a history of heart attack, mitral valve prolapse, left ventricular hypertrophy, or uncontrolled hypertension)

- Severe medical illness, such as AIDS, active hepatitis, significant hepatocellular

injury with either elevated total bilirubin levels greater than 1. 3 mg/dl or elevated aspartate aminotransferase (AST) and serum glutamic-pyruvic transaminase (SGPT) levels at least 3. 5 times above normal, after the required 3 days of abstinence

- History of hypersensitivity to modafinil or naltrexone

- Currently using any psychoactive medications, including any anti-seizure medications

(with the exception of diphenhydramine if used sparingly for sleep disturbance)

- Receiving chronic therapy with any drug known to interact adversely with either

modafinil or naltrexone, including propranolol, phenytoin, warfarin, or diazepam

- Has taken a monoamine oxidase inhibitor within the 30 days prior to study entry

- Has taken an investigational drug within the 60 days prior to study entry

- Has taken any opiate substitute (methadone, LAAM, buprenorphine) within the 60 days

prior to study entry

- Pregnant or breastfeeding

Donna Simpson, Phone: 215-243-9959

University of Pennsylvania, Philadelphia, Pennsylvania 19104 6178, United States; Recruiting
Kristi Varillo, MS, Phone: 215-222-3200, Email: varillo_k@mail.trc.upenn.edu

Starting date: February 2006
Ending date: May 2012
Last updated: November 3, 2008