Alcohol DependencePhase 2NCT01613014
ABT-436 for Alcohol Dependence
A Phase 2 study testing ABT-436 in people with Alcohol Dependence and Alcohol Abuse, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 5 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Alcohol Dependence, Alcohol Abuse, Alcohol Use Disorders
- What is being tested?
- ABT-436
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 5 sitesUnited States
- Study dates
- Feb 2013to Jul 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
- Current, past, or lifetime diagnosis of psychotic disorders (note schizophrenia is diagnosed under the psychotic disorder module of the MINI)
- Current or past diagnosis of bipolar disorder,
Show all 16Show fewer
- Current or past year major depressive episode,
- Current (past 3 months) eating disorder (anorexia or bulimia), or
- Current (within past year) diagnosis of panic disorder with or without agoraphobia,
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21224
Boston Medical Center
Boston, Massachusetts, 02118
University of Virginia
Charlottesville, Virginia, 22911
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Boston Medical Center
Quincy, Massachusetts
About this study
Official title: A Phase 2, Double-Blind, Randomized, Placebo Controlled Trial to Assess the Efficacy of ABT-436 for Alcohol Dependence
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.
Read the 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
- Being tested
- ABT-436, Matched Placebo - Sugar Pill
- Keywords
- Alcohol, Alcohol Dependence, Alcohol Abuse, Alcohol Use Disorders, Alcoholism
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABT-436Drug
Target dose - 400mg BID
Matched Placebo - Sugar PillDrug
Target Dose - 2 pills BID
| Study group | Role | What they receive |
|---|---|---|
| Sugar Pill | Placebo comparator | Matched Placebo sugar pill - target dose 2 pills BID Receives: Drug: Matched Placebo - Sugar Pill |
| ABT-436 | Active comparator | ABT-436 Target dose of 400 mg BID Receives: Drug: ABT-436 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 (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.
Measured: Weeks 2-12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2012 (estimated)
- Study startFeb 2013
- Primary completionMay 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alcohol DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Collaborators
- AbbVie
- Responsible party
- Sponsor
- Investigators
- Raye Litten, PhD, Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01613014
- Sponsor's protocol ID
- NCIG-004
- Status last verified
- Feb 2017
- First submitted
- 4 Jun 2012
- Last updated
- 4 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Randomized, Placebo Controlled Trial to Assess the Efficacy of ABT-436 for Alcohol Dependence
- ClinicalTrials.gov ID
- NCT01613014
- Acronym / sponsor ID
- NCIG-004
- Conditions
- Alcohol Dependence, Alcohol Abuse, Alcohol Use Disorders, Alcoholism
- Keywords
- Alcohol, Alcohol Dependence, Alcohol Abuse, Alcohol Use Disorders, Alcoholism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Collaborators
- AbbVie
- Study start
- Feb 2013
- Primary completion
- May 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 6 Jun 2012 (estimated)
- Results
- Posted 4 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sugar Pill | Placebo comparator | Drug: Matched Placebo - Sugar PillMatched Placebo sugar pill - target dose 2 pills BID |
| ABT-436 | Active comparator | Drug: ABT-436ABT-436 Target dose of 400 mg BID |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (16 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABT-436Target dose - 400mg BID | Drug | ABT-436 |
| Matched Placebo - Sugar PillTarget Dose - 2 pills BID | Drug | Sugar Pill |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Alcohol Dependence
RecruitingPhase 1
Environment and Alcohol: A Pilot Study
Alcohol Use Disorder
Not yet recruiting
Investigation of the Gut-Brain Axis in Alcohol Use Disorder
Alcohol Use Disorder (AUD), Alcohol Abstinence
Active, not recruiting
Leveraging Virtual Care Strategies to Improve Access and Treatment for Individuals With Alcohol Use Disorders
Alcohol Use Disorder
RecruitingObservational study
SMART-r: Substance Monitoring and Active Relapse Tracking Repository
Alcoholism, Substance-Related Disorders
RecruitingObservational study
NIAAA Natural History Protocol
Alcohol Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raye Litten, PhD principal investigator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ABT-436 in people with Alcohol Dependence and Alcohol Abuse, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weekly Percentage of Heaving Drinking Days (time frame: Weeks 2-12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2017.