NCT01613014

ABT-436 for Alcohol Dependence

A Phase 2, Double-Blind, Randomized, Placebo Controlled Trial to Assess the Efficacy of ABT-436 for Alcohol Dependence

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (actual)
• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) · NIH
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The primary efficacy endpoint examines the hypothesis that ABT-436 will decrease the weekly percentage of heavy drinking days during Study Weeks 2 through 12 (Days 8-84) as compared to placebo. A "heavy drinking day" is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men.

Detailed description

Adrenocorticotropic hormone (ACTH) release from the pituitary gland via V1B stimulation is central to the hypothalamus-pituitary-adrenal (HPA) axis stress response (Carrasco \& Van de Kar-2003, Herman \& Cullinan-1997, Sapolsky et al-2000; Tsigos \& Chrousos-2002). Chronic dysregulation of the HPA axis is common in major depressive disorder, anxiety disorders, and substance abuse disorders characterized by elevated AVP, increased responsiveness to AVP, as well as either increased or decreased overall HPA axis activity or responsiveness (Dinan \& Scott-2005). HPA axis normalization via pituitary V1B antagonism is a mechanism for potential ABT-436 efficacy in these disorders (Schüle et al-2009). Limbic V1B antagonism in the brain may also contribute to efficacy (Roper et al-2011). Alcohol dependence, or alcoholism, is characterized by a chronic relapsing course, in which alcohol-associated cues and stress are known relapse triggers (Brownell et al-1986, Heilig \& Egli-2006, Sinha \& Li-2007). Recent research suggests that neural systems mediating behavioral stress responses may offer useful targets for pharmacotherapy of alcoholism. In animal models, excessive alcohol consumption that results from a history of alcohol dependence is accompanied by increased behavioral sensitivity to stress (Heilig \& Koob-2007). Preclinical studies have shown that V1B antagonists can attenuate reinstatement of heroin and alcohol self-administration, and block dependence-induced exaggeration of alcohol intake, in rats. V1B antagonists have also been shown to block stress-induced reinstatement of drug and alcohol seeking in ethanol dependent rats (Zhou-2011). For these reasons the NIAAA Clinical Investigations Group (NCIG) proposes to test ABT-436 in a Phase 2, proof of concept trial for the treatment of alcohol dependence.

Conditions

• Alcohol Dependence
• Alcohol Abuse
• Alcohol Use Disorders
• Alcoholism

Interventions

Type	Name	Description
DRUG	ABT-436	Target dose - 400mg BID
DRUG	Matched Placebo - Sugar Pill	Target Dose - 2 pills BID

Timeline

• Start date: 2013-02-01
• Primary completion: 2015-05-01
• Completion: 2015-07-01
• First posted: 2012-06-06
• Last updated: 2017-04-04
• Results posted: 2017-04-04

Locations

5 sites across 1 country: United States