Stress, Hypothalamic-pituitary-adrenal (HPA) Dysfunction, and Relapse in Alcoholism

January 2, 2013 updated by: Bryon H Adinoff, University of Texas Southwestern Medical Center

Stress, HPA Dysfunction, and Relapse in Alcoholism

This proposal is part of the INIA Stress Consortium. This study will

  1. explore the contributions of lifetime trauma, recent stress, and alcohol use on stress-hormone axis disruption in treatment seeking, one-month abstinent, alcohol-dependent subjects
  2. assess the combined contributions of stress-hormone axis disruption and episodic stress on the risk of prospective drinking following treatment
  3. determine the role of neurosteroids in alcohol use.

Study Overview

Status

Completed

Conditions

Detailed Description

The hypothalamic-pituitary-adrenal (HPA) system is suggested as a key biologic link in stress-induced relapse. The HPA axis provides a regulatory feedback network between the brain and the body's behavioral and physiologic responses to stress, recovery, and adaptation. Both trauma and chronic alcohol use produce persistent disturbances in the HPA response to stress. The chronic use of alcohol may also impair the stress-induced release of neurosteroids, compounds that directly modulate central nervous system activity. Thus, altered cortisol and neurosteroid responsiveness during abstinence may impair the central nervous system's ability to mount an appropriate response to environmental stressors, heightening the probability of relapse. However, the relationship between stress, relapse, and HPA axis disturbances remains tentative. In the proposed study, the investigators will assess the contribution of trauma, stress, and alcohol use upon pituitary-adrenocortical functioning in alcohol dependence. The relative contribution of adrenocortical disruption and episodic stress to prospective drinking behaviors will then be determined.

Hypothesis: We hypothesize (1) that lifetime trauma, recent stress, and chronic alcohol use will additively contribute to HPA axis disruption, (2) alterations in glucocorticoid and neurosteroid release as well as episodic stress will predict a return to drinking.

Methods: One hundred treatment-seeking, one-month abstinent, alcohol-dependent subjects will be studied. Standardized assessments will be used to assess childhood and adult trauma as well as recent (six months) stress. Pituitary-adrenal (including ACTH (adrenocorticotropin), cortisol, and neurosteroids) responses to both neuroendocrine [ovine corticotropin releasing hormone (oCRH), cosyntropin, and dexamethasone] and experiential (public speaking) challenges will be measured. Drinking behavior and episodic stress will be prospectively assessed for six months following neuroendocrine assessment.

Significance: If our hypotheses are supported, a definitive connection between previous trauma, biological stress response mechanisms, and ongoing stress upon prospective drinking behavior will be demonstrated. The identification of a specific biologic mechanism that underlies this association will provide a fertile framework for the development of targeted pharmacological interventions to decrease relapse in this vulnerable population. In addition, elucidating the concurrent contributions of stress-response biologic systems and externals stressors will provide the therapist and patient with a constellation of specific risk factors for focused treatment.

Study Type

Observational

Enrollment (Actual)

75

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390-8564
        • UT Southwestern Medical Center at Dallas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

Inpatient treatment facility for substance use disorders.

Description

Inclusion Criteria:

  • Diagnosis of alcohol dependence

Exclusion Criteria:

  • Medical or psychiatric disorders that may effect stress-hormone axis functioning.
  • Medications that may effect stress-hormone axis functioning.
  • English speaking.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
alcohol dependence
Alcohol-dependent subjects currently being treated in an inpatient treatment facility.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Examine the contributions of previous trauma, recent stress, and chronic alcohol use to the stress-hormone axis reactivity in one-month abstinent alcohol-dependent subjects.
Time Frame: one month
one month

Secondary Outcome Measures

Outcome Measure
Time Frame
Assess the ability of stress-hormone axis reactivity and ongoing stress to predict subsequent drinking behavior following treatment discharge.
Time Frame: Six months
Six months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Dallas VA Medical Center

Investigators

  • Principal Investigator: Bryon Adinoff, MD, UT Southwestern Medical Center at Dallas and VA North Texas Health Care System

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (ACTUAL)

August 1, 2011

Study Completion (ACTUAL)

March 1, 2012

Study Registration Dates

First Submitted

June 19, 2008

First Submitted That Met QC Criteria

August 29, 2008

First Posted (ESTIMATE)

September 1, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

January 3, 2013

Last Update Submitted That Met QC Criteria

January 2, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AA016668
  • U01AA016668 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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