Acute Effects of Cortisol on Alcohol Craving in Alcohol Dependence (CAR-Bern 2013)

To investigate the effects of cortisol on alcohol craving and stress reactivity in alcohol addicted subjects.

Randomized, double-blind, placebo-controlled, cross-over, single administration of study medication.

Study hypothesis: Cortisol has an inhibiting effect on alcohol craving and stress reactivity in alcohol dependent subjects.

Study Overview

• Status: Completed
• Conditions: Psychological Stress; Physiological Stress; Alcohol Craving
• Intervention / Treatment: Drug: Cortisol 20mg; Drug: Placebo Mannitol

Detailed Description

Background

Alcohol dependence is a chronically and relapsing disorder with major impact on the persons psychological, physiological and social functioning. There is extensive evidence from animal and human studies pointing out the important role of addiction memory in the development and maintenance of the disorder.

Cognitive behavioural therapy (CBT) has proven its high effectiveness in the treatment for addictive disorders. A core element of CBT are exposure techniques that are comparable to extinction and habituation learning. The repeated exposure to alcohol related cues in the absence of alcohol ingestion will lead to extinction of conditioned responses, thus reducing the probability of relapse to alcohol taking behaviour.

Studies have shown that glucocorticoids impair memory retrieval in healthy subjects. In fact, the investigators could show that cortisol has a fear reducing effect in patients with post-traumatic stress disorder and in phobic patients, resulting particularly in reduced symptoms of anxiety and in reduced stress reactivity. Interestingly enough, pharmacologically induced high levels of glucocorticoids lowered the subjective feeling of anxiety and stress in situations activating per se the HPA-axis. Further it has been shown that the combined therapy of glucocorticoid administration and exposition based psychotherapy leads to better therapy outcome in patients with specific phobias.

Objective

The goal of this study is to examine the acute effects of glucocorticoids administration on alcohol craving and stress reactivity of abstinent alcohol dependent patients. On the basis of clinical research in anxiety disorders, the investigators expect that a pharmacologically increased cortisol level may impair the retrieval of addiction memory, which is indicated by less craving during the alcohol exposition, while exposition therapy enhances consolidation of corrective experiences. Similar to the research in anxiety patients, the investigators aim to examine whether cortisol administration could help improve the effects of exposition therapy in patients with alcohol dependence. The purpose is to decrease therapy duration through cortisol administration in addition to already well proven therapies and make the therapy more efficient as well as a factor in reducing healthcare costs.

Methods

Patients undergo two identical experimental sessions between the 6th and 8th week (one week in between) of their 12-week inpatient treatment program for alcohol dependence. The experiment takes place in the experimental rooms of the clinic Südhang between 1 and 6 pm. One hour before the confrontation with alcohol associated stimuli patients receive either 20mg of hydrocortisone or placebo (oral administration). The experiment consists of a computer based picture task (alcoholic and neutral pictures) and an in-vivo exposure task. Psychological (craving, stress, arousal) and physiological (heart rate, saliva cortisol) parameters are repeatedly measured over the course of the experiment.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Bern
    • Kirchlindach, Bern, Switzerland, CH-3038
      • Klinik Südhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18
• Abstinent alcoholics in the 12-week in-patient program of the Clinic Südhang
• Abstained from alcohol for at least 6 weeks
• Voluntarily signed informed consent

Exclusion Criteria

• Co-morbid psychiatric disturbances (such as major depression, bipolar disorder, schizophrenia)
• Current medical conditions excluding participation (such as acute infectious disease)
• Recent history of systemic or topic glucocorticoid therapy
• Known hypersensitivity to the IMP under investigation (cortisol)
• Pregnancy, breast-feeding
• Inability to read and understand the participant's information
• Positive alcohol test according to breathalyser

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cortisol first, Placebo second; Drug: Cortisol 20mg, Drug: Mannitol (used as placebo)	Drug: Cortisol 20mg; Drug: Cortisol 20mg; Drug: Placebo Mannitol; Drug: Placebo Mannitol
Active Comparator: Placebo first, Cortisol second; Drug: Cortisol 20mg, Drug: Mannitol (used as placebo)	Drug: Cortisol 20mg; Drug: Cortisol 20mg; Drug: Placebo Mannitol; Drug: Placebo Mannitol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in alcohol craving score	Measured by Alcohol Urge Questionnaire & Visual Analogue Scale	During and after presentation of drug stimuli, expected to be after 10 minutes

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in State-Trait-Anger Expression Inventory STAXI	After presentation of drug stimuli, expected to be after 20 minutes
Change from baseline in heart rate variability	During and after presentation of drug stimuli, expected to be after 10 minutes
Saliva Cortisol Level	After presentation of drug stimuli, expected to be after 90 minutes

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Study Director: Leila Soravia, Dr. phil., University Hospital of Psychiatry Bern; Principal Investigator: Peter Allemann, Dr. med., Clinic Südhang; Study Chair: Dominique de Quervain, Prof. Dr., University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: July 17, 2014
• First Submitted That Met QC Criteria: July 18, 2014
• First Posted (Estimate): July 21, 2014

Study Record Updates

• Last Update Posted (Estimate): June 24, 2015
• Last Update Submitted That Met QC Criteria: June 23, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Alcohol Dependence; Cortisol; Alcohol Craving
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Stress, Psychological; Physiological Effects of Drugs; Anti-Inflammatory Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Mannitol; Hydrocortisone
• Other Study ID Numbers: 068/14