Cocaine Rapid Efficacy Screening Trial (CREST): a paradigm for the controlled evaluation of candidate medications for cocaine dependence.
OBJECTIVE
Development of effective medications for the treatment of cocaine dependence remains a major priority for the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. The Cocaine Rapid Efficacy Screening Trial (CREST) paradigm was developed by the Division of Treatment Research and Development (DT R&D) at NIDA with the goal of enhancing pilot clinical trial validity when systematically assessing a range of medications and drug classes for potential utility in treatment of cocaine dependence.


METHODS
CREST utilizes a randomized, controlled, parallel group, blinded methodology for comparing one or more marketed medications against a standard, pharmaceutical grade placebo. The trial design is comprised of a flexible 24-week screening/baseline period followed by randomization to an 8-week treatment period.


METHODS
Standard measures of outcomes for the CREST included urinary benzoylecgonine (primary metabolite of cocaine), retention, cocaine craving, depression, clinical global impression and HIV-risk behaviors. In order to facilitate comparisons of data from the CREST studies across sites, drug classes and time, standardized procedures, measures and psychosocial counseling were used.


RESULTS
A total of 19 medications were evaluated in out-patient treatment research clinics in Boston, Cincinnati, Los Angeles, New York and Philadelphia.


CONCLUSIONS
Findings supported decisions to move forward three medications (cabergoline, reserpine, tiagabine) using full-scale, adequately powered, randomized placebo-controlled trial designs. Lessons learned from the CREST experience continue to shape cocaine pharmacotherapy trial design and execution.
Leiderman
Deborah B
DB
Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA. leidermand@cder.fda.gov
Shoptaw
Steve
S
Montgomery
Ann
A
Bloch
Daniel A
DA
Elkashef
Ahmed
A
LoCastro
Joseph
J
Vocci
Frank
F
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000077465:Cabergoline; D019970:Cocaine-Related Disorders / Q000534:rehabilitation*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D004873:Ergolines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000627:therapeutic use*; D009557:Nipecotic Acids / Q000627:therapeutic use*; D011446:Prospective Studies; D015203:Reproducibility of Results; D012110:Reserpine / Q000627:therapeutic use*; D000078308:Tiagabine
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D004873:Ergolines; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D012110:Reserpine; D000077465:Cabergoline; D000078308:Tiagabine