Aripiprazole to Reduce Cocaine Relapse
Condition: Cocaine-Related Disorders
MeSH terms: Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      Despite the many behavioral and cognitive treatment therapies that exist for cocaine
      addiction, individuals who complete cocaine abuse treatment are still at high risk for
      relapsing. Aripiprazole, a medication that is currently used to treat schizophrenia, may be
      useful in preventing drug relapse in individuals addicted to cocaine. This three-part study
      will evaluate the interaction between aripiprazole and cocaine. It will also determine the
      safety and effectiveness of aripiprazole in preventing drug relapse among cocaine addicts.
    

Detailed description: 
      Cocaine addiction is a serious health problem with no available medical treatment for
      preventing relapse. Cocaine abusers often report that upon attempting to demonstrate control
      over the drug by only "sampling" it following a period of abstinence, they are more likely to
      relapse. These small "sampling" amounts of cocaine are thought to function as priming doses.
      Priming doses act as a stimulus in the brain to signal that there is more cocaine available,
      which in turn may lead to further cocaine use. Medications that reduce the stimulating effect
      of the cocaine priming dose may be useful in preventing cocaine relapse. Aripiprazole, a
      medication that is currently used to treat schizophrenia, may be effective at reducing
      relapse in individuals addicted to cocaine. By enhancing activity of the brain chemicals
      dopamine and serotonin, aripiprazole may counter the effects of cocaine and also reduce
      cocaine cravings.

      This study will involve three sequential experiments. Experiment 1 will evaluate the
      physiological and behavioral effects of various combinations of cocaine and aripiprazole.
      Experiment 2 will evaluate the capability of aripiprazole at reducing the stimulating effects
      of cocaine. Lastly, Experiment 3 will evaluate the role of cocaine priming doses on
      subsequent cocaine use and how aripiprazole might alter the effect of the priming dose. In
      turn, these findings may lead to future clinical trials using aripiprazole to treat cocaine
      addiction and prevent relapse.

      All three experiments will involve inpatient hospital stays. Participants will be required to
      refrain from using any non-study drugs, other than nicotine, and will undergo daily urine and
      breathalyzer tests. Questionnaires will be used to assess drug effects and cocaine cravings,
      and a computerized test will measure motor function and performance. Heart rate and blood
      pressure will be monitored periodically; an electrocardiogram (ECG) will record continuously
      to monitor heart electrical activity. Following the end of each experiment, all participants
      will be offered a referral to a drug abuse treatment program.

      The first experiment will last 9 weeks and will enroll 8 individuals addicted to cocaine.
      Participants will take part in daily sessions in which they will receive varying doses of
      cocaine and aripiprazole, alone and in combination. This will provide important information
      regarding the safety and tolerability of cocaine-aripiprazole combinations.

      The second experiment will last 10 weeks and will enroll 12 individuals addicted to cocaine.
      Participants will take part in various phases, which will each last several days. The phases
      will include a cocaine sampling phase; a cocaine acquisition phase in which participants will
      receive monetary rewards for distinguishing between cocaine and placebo; a placebo phase; an
      aripiprazole maintenance phase; a cocaine dose response phase in which the ability of
      aripiprazole to reduce cocaine's stimulating effects will be examined; and a washout phase in
      which no drugs will be given. Cocaine and aripiprazole doses will be determined by the
      results of the first experiment.

      The third experiment will last 8 weeks and will enroll 12 individuals addicted to cocaine. A
      self-administration procedure designed to model relapse will be used to assess the effects of
      priming doses of cocaine on subsequent cocaine-taking behavior, alone and following
      aripiprazole treatment. Participants will be assigned to receive placebo for the first part
      of the study followed by aripiprazole for the remainder of the study or vice versa. During
      experimental sessions, participants will receive a specified amount of cocaine, which will
      act as the priming dose. Next, participants will choose between receiving either another
      similar dose of cocaine or money. This will be followed by a washout phase and then several
      more sampling-choice sessions with differing amounts of cocaine. Cocaine and aripiprazole
      doses will be determined by the results of the first experiment.
    

Intervention name(s): Aripiprazole; Placebos
Intervention type(s): Drug; Drug
Intervention description(s): Aripiprazole; 0-30 mg; oral; daily; Placebo; 0 mg; oral; daily
Other intervention name(s): Abilify
Intervention MeSH terms: Aripiprazole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cocaine Addiction; Cocaine Dependence