DBH gene as predictor of response in a cocaine vaccine clinical trial.
Neurosci Lett
; 541: 29-33, 2013 Apr 29.
Article
em En
| MEDLINE
| ID: mdl-23458673
ABSTRACT
We examined a pharmacogenetic association of the dopamine ß-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 DßH level genotype dropped from 77% to 51% on vaccine (p=0.0001), while those with the normal DßH 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vacinas
/
Toxina da Cólera
/
Cocaína
/
Transtornos Relacionados ao Uso de Cocaína
/
Dopamina beta-Hidroxilase
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos