ABT-436 for Alcohol Dependence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01613014
Recruitment Status : Completed
First Posted : June 6, 2012
Results First Posted : April 4, 2017
Last Update Posted : April 4, 2017
Information provided by (Responsible Party):
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Brief 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.

Condition or disease Intervention/treatment Phase
Alcohol Dependence Alcohol Abuse Alcohol Use Disorders Alcoholism Drug: ABT-436 Drug: Matched Placebo - Sugar Pill Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Double-Blind, Randomized, Placebo Controlled Trial to Assess the Efficacy of ABT-436 for Alcohol Dependence
Study Start Date : February 2013
Actual Primary Completion Date : May 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Sugar Pill
Matched Placebo sugar pill - target dose 2 pills BID
Drug: Matched Placebo - Sugar Pill
Target Dose - 2 pills BID

Active Comparator: ABT-436
ABT-436 Target dose of 400 mg BID
Drug: ABT-436
Target dose - 400mg BID

Primary Outcome Measures :
  1. Weekly Percentage of Heaving Drinking Days [ Time Frame: Weeks 2-12 ]

    The primary objective of this study is to assess the efficacy of ABT-436 to reduce the weekly percentage of heavy drinking days (reduction in drinking) in subjects with alcohol dependence confirmed by DSM-IV-TR criteria. A "heavy drinking day" is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men.

    The outcome measure was averaged across weeks 2-12.

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Be at least 21 years of age and no more than 65 years of age.
  • Have a current (past 12 months) DSM-IV-TR diagnosis of alcohol dependence.
  • Be seeking treatment for alcohol dependence and desire a reduction or cessation of drinking.

Exclusion Criteria:

  • current (past 12 months) abuse or dependence on any psychoactive substance other than alcohol, caffeine and nicotine, including sedatives and hypnotics, as defined by DSM-IV-TR criteria.
  • positive urine toxicology screen performed during screening or baseline.
  • been hospitalized for alcohol intoxication delirium, alcohol withdrawal delirium, alcohol-induced persisting dementia or amnestic disorder, or have had an alcohol withdrawal seizure, alcohol-induced psychotic disorder with a primary diagnosis of alcohol dependence or a history of any seizure disorder.
  • Have any of the following, based on DSM-IV-TR criteria as assessed using the MINI:

    1. Current, past, or lifetime diagnosis of psychotic disorders (note schizophrenia is diagnosed under the psychotic disorder module of the MINI)
    2. Current or past diagnosis of bipolar disorder,
    3. Current or past year major depressive episode,
    4. Current (past 3 months) eating disorder (anorexia or bulimia), or
    5. Current (within past year) diagnosis of panic disorder with or without agoraphobia,
    6. Anti-social personality disorder.
  • Have any underlying medical condition that could exacerbate during trial participation causing hospitalization, surgery, and/or the need to use exclusionary medications to treat condition.
  • Be pregnant or breast-feeding or have plans to become pregnant at any time during the study.
  • Have a clinically significant abnormal laboratory value;
  • Hemoglobin A1c value > 7%.
  • Have a clinically significant ECG as determined by the investigator or abnormal ECG heart rate (<45 or > 100 bpm or QTc interval corrected for heart rate using the Fridericia formula (QTcF) > 450 msec.
  • Have HIV or Hepatitis A, B or C.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01613014

United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21224
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Boston Medical Center
Quincy, Massachusetts, United States
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22911
Sponsors and Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Principal Investigator: Raye Litten, PhD National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Responsible Party: National Institute on Alcohol Abuse and Alcoholism (NIAAA) Identifier: NCT01613014     History of Changes
Other Study ID Numbers: NCIG-004
First Posted: June 6, 2012    Key Record Dates
Results First Posted: April 4, 2017
Last Update Posted: April 4, 2017
Last Verified: February 2017

Keywords provided by National Institute on Alcohol Abuse and Alcoholism (NIAAA):
Alcohol Dependence
Alcohol Abuse
Alcohol Use Disorders

Additional relevant MeSH terms:
Alcohol Drinking
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Drinking Behavior
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs