DBH gene as predictor of response in a cocaine vaccine clinical trial

• Published in: Neuroscience letters Vol. 541; pp. 29 - 33
• Main Authors: Kosten, Thomas R., Domingo, Coreen B., Hamon, Sara C., Nielsen, David A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 29.04.2013
• Subjects: Adolescent; Adult; Cholera Toxin - immunology; Clinical Trials, Phase II as Topic; Cocaine; Cocaine - analogs & derivatives; Cocaine - immunology; Cocaine - urine; Cocaine-Related Disorders - genetics; Cocaine-Related Disorders - immunology; Cocaine-Related Disorders - prevention & control; Dopamine; Dopamine beta-Hydroxylase - genetics; Female; Gene; Humans; Male; Middle Aged; Polymorphism; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Treatment; Treatment Outcome; Vaccine; Vaccines - immunology; Young Adult; Cocaine; Vaccine; Dopamine; Treatment; Gene; Polymorphism
• ISSN: 0304-3940; 1872-7972; 1872-7972
• DOI: 10.1016/j.neulet.2013.02.037

► Cocaine vaccine pharmacotherapy reduced cocaine-free urines of cocaine dependent addicts. ► Cocaine vaccine was effective in patients with low activity dopamine β-hydroxylase genotypes. ► Mechanism may involve greater cocaine induced paranoia in patients with low activity DβH. We examined a pharmacogenetic association of the dopamine β-hydroxylase (DBH) gene with a response to an anti-cocaine vaccine that was tested in a recent clinical trial. This gene is associated with cocaine-induced paranoia, which has a slower onset than the euphoria from cocaine. The vaccine reduced euphoria by slowing the entry of cocaine into the brain, but it may not reduce aversive symptoms like paranoia. A 16-week Phase IIb randomized double-blind placebo-controlled trial of 114 cocaine and opioid dependent subjects who received five vaccinations over the first 12 weeks was examined. We genotyped 71 subjects for the rs1611115 (-1021C>T) variant of the DBH gene and compared vaccine to placebo subjects on cocaine-free urines. Using repeated measures analysis of variance, corrected for population structure, vaccine pharmacotherapy reduced cocaine positive urines significantly based on DBH genotype. Patients with the low DβH level genotype dropped from 77% to 51% on vaccine (p=0.0001), while those with the normal DβH level genotype dropped from 83% to 72%. Placebo showed no effect on cocaine use overall or by genotype. This study indicates that a patient's DBH genotype could be used to identify a subset of individuals for whom vaccine treatment may be an effective pharmacotherapy for cocaine dependence.