A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence

Megan L. Ryan, Daniel E. Falk, Joanne B. Fertig, Beatrice Rendenbach-Mueller, David A. Katz, Katherine A. Tracy, Eric C Strain, Kelly Dunn, Kyle Kampman, Elizabeth Mahoney, Domenic A. Ciraulo, Laurie Sickles-Colaneri, Nassima Ait-Daoud, Bankole A. Johnson, Janet Ransom, Charles Scott, George F. Koob, Raye Z. Litten

Research output: Contribution to journalArticle

Abstract

Alcohol use disorder has been linked to dysregulation of the brain stress systems, producing a negative emotional state leading to chronic relapsing behavior. Vasopressin receptors appear to have a regulatory role in stress, anxiety, and alcohol. This study evaluated the novel compound, ABT-436, a V1b receptor antagonist, in alcohol-dependent participants in a 12-week clinical trial. Men and women (n=150) who met criteria for DSM–IV alcohol dependence were recruited across four sites. Participants received double-blind ABT-436 or placebo, and a computerized behavioral intervention. ABT-436 was titrated to 800 mg/day during weeks 2–12. Although the primary outcome, percentage of heavy drinking days, was lower in participants receiving ABT-436 compared with placebo, this difference was not statistically significant (31.3 vs 37.6, respectively; p=0.172; d=0.20). However, participants receiving ABT-436 had significantly greater percentage of days abstinent than those receiving placebo (51.2 vs 41.6, respectively; p=0.037; d=0.31). No significant differences were found between treatment groups on any other measures of drinking, alcohol craving, or alcohol-related consequences. Smokers receiving ABT-436 smoked significantly fewer cigarettes per week than those receiving placebo (p=0.046). ABT-436 was well tolerated, with diarrhea (mild-to-moderate severity) being the most common side effect. In subgroup analyses, participants with relatively higher baseline levels of stress responded better to ABT-436 than placebo on select drinking outcomes, suggesting there may be value in testing medications targeting the vasopressin receptor in high stress, alcohol-dependent patients.Neuropsychopharmacology advance online publication, 19 October 2016; doi:10.1038/npp.2016.214.

Original languageEnglish (US)
JournalNeuropsychopharmacology
DOIs
StateAccepted/In press - Oct 19 2016

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Alcoholism
Randomized Controlled Trials
Placebos
Alcohols
Vasopressin Receptors
Drinking
Tobacco Products
Alcohol Drinking
Publications
Diarrhea
Anxiety
Clinical Trials
Brain
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence. / Ryan, Megan L.; Falk, Daniel E.; Fertig, Joanne B.; Rendenbach-Mueller, Beatrice; Katz, David A.; Tracy, Katherine A.; Strain, Eric C; Dunn, Kelly; Kampman, Kyle; Mahoney, Elizabeth; Ciraulo, Domenic A.; Sickles-Colaneri, Laurie; Ait-Daoud, Nassima; Johnson, Bankole A.; Ransom, Janet; Scott, Charles; Koob, George F.; Litten, Raye Z.

In: Neuropsychopharmacology, 19.10.2016.

Research output: Contribution to journalArticle

Ryan, ML, Falk, DE, Fertig, JB, Rendenbach-Mueller, B, Katz, DA, Tracy, KA, Strain, EC, Dunn, K, Kampman, K, Mahoney, E, Ciraulo, DA, Sickles-Colaneri, L, Ait-Daoud, N, Johnson, BA, Ransom, J, Scott, C, Koob, GF & Litten, RZ 2016, 'A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence', Neuropsychopharmacology. https://doi.org/10.1038/npp.2016.214
Ryan, Megan L. ; Falk, Daniel E. ; Fertig, Joanne B. ; Rendenbach-Mueller, Beatrice ; Katz, David A. ; Tracy, Katherine A. ; Strain, Eric C ; Dunn, Kelly ; Kampman, Kyle ; Mahoney, Elizabeth ; Ciraulo, Domenic A. ; Sickles-Colaneri, Laurie ; Ait-Daoud, Nassima ; Johnson, Bankole A. ; Ransom, Janet ; Scott, Charles ; Koob, George F. ; Litten, Raye Z. / A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence. In: Neuropsychopharmacology. 2016.
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abstract = "Alcohol use disorder has been linked to dysregulation of the brain stress systems, producing a negative emotional state leading to chronic relapsing behavior. Vasopressin receptors appear to have a regulatory role in stress, anxiety, and alcohol. This study evaluated the novel compound, ABT-436, a V1b receptor antagonist, in alcohol-dependent participants in a 12-week clinical trial. Men and women (n=150) who met criteria for DSM–IV alcohol dependence were recruited across four sites. Participants received double-blind ABT-436 or placebo, and a computerized behavioral intervention. ABT-436 was titrated to 800 mg/day during weeks 2–12. Although the primary outcome, percentage of heavy drinking days, was lower in participants receiving ABT-436 compared with placebo, this difference was not statistically significant (31.3 vs 37.6, respectively; p=0.172; d=0.20). However, participants receiving ABT-436 had significantly greater percentage of days abstinent than those receiving placebo (51.2 vs 41.6, respectively; p=0.037; d=0.31). No significant differences were found between treatment groups on any other measures of drinking, alcohol craving, or alcohol-related consequences. Smokers receiving ABT-436 smoked significantly fewer cigarettes per week than those receiving placebo (p=0.046). ABT-436 was well tolerated, with diarrhea (mild-to-moderate severity) being the most common side effect. In subgroup analyses, participants with relatively higher baseline levels of stress responded better to ABT-436 than placebo on select drinking outcomes, suggesting there may be value in testing medications targeting the vasopressin receptor in high stress, alcohol-dependent patients.Neuropsychopharmacology advance online publication, 19 October 2016; doi:10.1038/npp.2016.214.",
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