The purpose of this CREST (Clinical Rapid Evaluation Screening Trial) study is the treatment
of cocaine dependence using reserpine, gabapentin, or lamotrigine vs. an unmatched placebo
Considerable progress in preclinical research has provided a basis for hypothesis driven
clinical trials in cocaine dependence. A greater mechanistic understanding of both cocaine
and many clinically approved medications has led to the identification of many promising
medications for the treatment of cocaine dependence.
For this reason NIDA has developed a CREST (Clinical Rapid Evaluation Screening Trial)
protocol to provide a needed incremental medication screening step between preclinical
research and full blown expensive Phase III pivotal trials. While patients receive manual
based psychotherapy, three medications are screened compared to unmatched placebo in an
eight-week, 60-subject, four cell design trial. Other important features of the CREST
protocol include collecting baseline measurements over a two week period and analyzing
primary outcome measures (quantitative urine toxicology and clinical global improvement
scales) in terms of a composite score of overall individual patient improvement.
The three medications being evaluated in this trial include reserpine, gabapentin and
lamotrigine. Reserpine is being screened because of its well-known preclinical ability to
functionally antagonize cocaine (by depleting neurochemicals elevated by cocaine).
Gabapentin and lamotrigine are hypothesized to interfere with glutamatergic cocaine
sensitization/kindling mechanisms relevant to addiction.
1. Males and females, 18 to 59 years of age.
2. DSM-IV diagnosis of cocaine dependence as determine by a semi-structured clinical
3. Subjects must have at least two cocaine-positive urines (BE level >300 ng/ml) during
the two week screening phase of the study.
4. Subjects must have a self reported use of at least $100 worth of cocaine within the
past 30 days.
5. Ability to provide written informed consent and to comply with all study procedures.
6. Women of child-bearing capacity must be using one of the following acceptable methods
of birth-control: a. oral contraceptives, b. barrier (diaphragm or condom) with
spermicide, c. intrauterine progesterone contraceptive system, d. levonorgestrel
implant, e. medroxyprogesterone acetate contraceptive injection
1. Current dependence on any psychoactive substance other than cocaine, alcohol, or
nicotine, physiological dependence on alcohol requiring medical detoxification.
2. Subjects requiring treatment for neurological or psychiatric disorders.
3. Subjects with any potentially life threatening or progressive medical illness other
4. Subjects with a history of hypertension currently requiring treatment.
5. Subjects who have received a drug with known potential for toxicity to a major organ
system within the month prior to entering treatment or who have been on any
experimental medication within the past 60 days.
6. Females who are pregnant or lactating or having had three or more days of amenorrhea
beyond the time of expected menses at the time of the first dose of study medication.
7. Subjects who have clinically significant abnormal laboratory values as determined by
the principal investigator.
8. Subjects who have any disease of the gastrointestinal system, liver, or kidneys which
could result in altered metabolism or excretion of the study medication.
9. Chronic therapy with any medication which could interact adversely with one of the
medications under study.
10. Therapy with any of the opiate-substitutes (methadone, LAAM, buprenorphine) within 60
days of enrollment in this study.
11. Subjects with a seizure disorder or with a history of a seizure disorder other than
childhood febrile seizures or alcohol withdrawal seizures.
12. Subjects with a history of major depression.
13. Patients with a history of rashes or other sensitivity reactions to reserpine,
lamotrigine, or gabapentin.
14. Participant plans to receive psychosocial treatment external to that designated in
the protocol during study participation.
15. Subjects with systolic blood pressure below 100 mm of Hg., or diastolic blood
pressure below 60 mm of Hg., who are symptomatic as determined by the physician
conducting the screening medical history and phy