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

Alcohol Dependence Clinical Trial

Official title:

Stress, HPA Dysfunction, and Relapse in Alcoholism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00744588
• Other study ID #: AA016668
• Secondary ID: U01AA016668
• Status: Completed
• Phase: N/A
• First received: June 19, 2008
• Last updated: January 2, 2013
• Start date: August 2007
• Est. completion date: March 2012

Study information

• Verified date: January 2013
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: March 2012
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcoholism

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas

Sponsors (3)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Dallas VA Medical Center, National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		one month	No
Secondary	Assess the ability of stress-hormone axis reactivity and ongoing stress to predict subsequent drinking behavior following treatment discharge.		Six months	No