Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01613014
Other study ID # NCIG-004
Secondary ID
Status Completed
Phase Phase 2
First received June 4, 2012
Last updated March 8, 2016
Start date March 2013
Est. completion date May 2015

Study information

Verified date April 2015
Source National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug AdministrationUnited States: Data and Safety Monitoring BoardUnited States: Institutional Review Board
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 148
Est. completion date May 2015
Est. primary completion date May 2015
Accepts healthy volunteers No
Gender Both
Age group 21 Years to 65 Years
Eligibility 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

Drug:
ABT-436
Target dose - 400mg BID
Matched Placebo - Sugar Pill
Target Dose - 2 pills BID

Locations

Country Name City State
United States Johns Hopkins University School of Medicine Baltimore Maryland
United States Boston Medical Center Boston Massachusetts
United States University of Virginia Charlottesville Virginia
United States University of Pennsylvania Philadelphia Pennsylvania
United States Boston Medical Center Quincy Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
National Institute on Alcohol Abuse and Alcoholism (NIAAA) AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Reduction in the weekly percentage of heaving drinking days The primary objective of this study is to assess the efficacy of ABT-436 to reduce the weekly percentage of heavy drinking days 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. Weeks 2-12 No
See also
  Status Clinical Trial Phase
Recruiting NCT05054738 - CRP and S&A for Inpatient Veterans N/A
Completed NCT02233738 - Group Motivational Interviewing (GMI) For Homeless Veterans In VA Services N/A
Completed NCT05877807 - Effect of Baclofen to Prevent Post-Traumatic Stress Disorder
Completed NCT00000437 - Tobacco Dependence in Alcoholism Treatment (Nicotine Patch/Naltrexone) Phase 4
Completed NCT00536146 - The Stress-Hormone System in Alcohol-Dependent Subjects N/A
Terminated NCT00890149 - Ondansetron for the Treatment of Heavy Drinking Among Emerging Adults Phase 2
Completed NCT02179749 - Mifepristone Treatment of Alcohol Use Disorder Phase 2
Completed NCT02939352 - The Effects of Theta Burst Stimulation on the Brain Response to Drug and Alcohol Cues Early Phase 1
Completed NCT01553136 - Varenicline Treatment of Alcohol Dependence in Smokers Phase 2
Terminated NCT01408641 - Topiramate for Alcohol Use in Posttraumatic Stress Disorder N/A
Completed NCT01389297 - Overcoming Addictions: A Randomized Clinical Trial of a Web Application Based on SMART Recovery N/A
Completed NCT01113164 - Matching Genotypes and Serotonergic Medications for Alcoholism Phase 1
Completed NCT01760785 - Valproate for Mood Swings and Alcohol Use Following Head Injury N/A
Completed NCT00768508 - Combined Pharmacotherapies for Alcoholism Phase 3
Terminated NCT02842528 - Cognitive Vulnerability Factors in Alcohol-dependence N/A
Completed NCT00127231 - Brief Therapy Intervention for Heavy/Hazardous Drinking in HIV-Positive Women N/A
Completed NCT00367575 - An Internet-based Intervention for Problem Drinking N/A
Completed NCT00223639 - New Medications to Treat Alcohol Dependence Phase 2
Completed NCT00167687 - Prazosin Alcohol Dependence IVR Study Phase 4
Completed NCT00583440 - 12-step Facilitation for the Dually Diagnosed Phase 1/Phase 2