The development of pharmacological agents to manage cocaine dependence has been a long sought-after goal of the National Institute on Drug Abuse’s (NIDA) Medications Development Program. Despite several years of testing, there is no FDA-approved medication for the treatment of cocaine dependence. However, that may change in the coming years. Two medications, funded wholly or in part by NIDA, are currently undergoing testing in clinical trials in cocaine-dependent participants to confirm early reports of efficacy.
The first of these medications is vigabatrin, a drug that increases the levels of the chemical GABA in the brain. GABA has a calming effect, increasing relaxation and reducing stress and anxiety. Animal studies have shown that vigabatrin prevents behavioral manifestations of cocaine dependence, which provided an excellent rationale for testing vigabatrin in cocaine-dependent patients.
Initially, two open-label studies, in which both researchers and participants knew which drug is being administered, were conducted in Mexico by Drs. Emilia Figueroa, John Brodie, and Stephen Dewey. The studies showed a reduction or elimination of cocaine use in the cocaine-dependent study participants.
These studies were followed up by a randomized, placebo-controlled, double-blind trial of vigabatrin in cocaine users at a single clinic in Mexico by the same investigators. In that study, vigabatrin-treated participants were four times as likely to achieve abstinence as the placebo-treated participants.
A multicenter trial was then initiated in the U.S. The vigabatrin group did not achieve a greater abstinence rate than the placebo group. A retrospective analysis of vigabatrin levels in urine samples noted that medication adherence was poor: only 40 percent of the vigabatrin participants had taken the medication.
This prompted NIDA, the Veterans Administration (VA) and Catalyst Pharmaceutical Partners to join forces to fund another multicenter trial. In this current randomized, double-blind, placebo-controlled study, participants are being administered their medication in the clinic three times per week to ensure adherence to medication intake. Two hundred participants will be randomized in this study. Dr. Kathleen Brady of the Medical University of South Carolina is the Principal Investigator, Dr. Christopher Stock is the VA Chairman of the study and Dr. David McCann is the NIDA Study Chairman. The trial is expected to complete in July 2012.
NIDA is also funding a single-site trial of the safety and efficacy of vigabatrin for the treatment of cocaine and alcohol dependence at the University of Pennsylvania. Dr. Kyle Kampmann is the principal investigator. Sixty patients will be randomized to either vigabatrin or placebo. Expected to complete in July 2012, if the results of these studies replicate the findings of the single clinic trial conducted in Mexico, vigabatrin should be given serious consideration for filing a New Drug Application with the Food and Drug Administration.
The second medication of interest, being assessed by the NIDA Clinical Trials Network (CTN), is a combination of two approved medications, buprenorphine and naltrexone. The theory behind combining these medications is that together they affect brain receptors differently than either medication alone.
This study is a follow-up to two previous studies: a buprenorphine study in the U.S. conducted by Dr. Ivan Montoya that showed a reduction in cocaine use, as well as a study in Italy by Dr. Gilberto Gerra that showed that opiate- and cocaine-dependent patients who were withdrawn from opiates and then placed on a regimen of oral naltrexone and buprenorphine reduced both their opiate and cocaine use.
In the CTN trial, all prospective study participants must meet criteria for cocaine dependence and be opioid-experienced within the last year. After ensuring participants are not currently opioid dependent, they will be given an injection of Vivitrol (depot naltrexone). The 300 participants will then be randomized to receive either four milligrams of buprenorphine/naloxone, 16 milligrams of buprenorphine/naloxone, or placebo for eight weeks. All study participants will be given psychosocial therapy. A second Vivitrol injection will be given at the end of week four.
The primary outcome of the study is determining the reduction in cocaine as measured by self-report in the final 30 days of the study and confirmed by urine toxicology testing. Drs. Walter Ling and Larissa Mooney of UCLA and Dr. Andrew Saxon of the University of Washington are the principal investigators in this study. The trial is expected to complete in October 2013. Results of this Phase II study could guide further development of this combination.
Frank Vocci, PhD, is President of Friends Research Institute, which promotes health and well-being through research, grants administration, education and treatment.