Single-dose of Nalmefene to Modulate Neural Alcohol Cue Reactivity

Alcoholism Clinical Trial

— NALCUE  

Official title:

Nalmefene Challenge to Modulate Neural Reactivity to Alcohol-related and Emotional Cues in Non-treatment Seeking Alcohol Dependent Participants

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02372318
• Other study ID #: 37
• Status: Terminated
• Phase: Early Phase 1
• First received: February 6, 2015
• Last updated: June 28, 2017
• Start date: April 2015
• Est. completion date: May 2016

Study information

• Verified date: January 2016
• Source: Central Institute of Mental Health, Mannheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to use functional Magnetic Resonance Imaging (fMRI) to measure neural reactivity to alcohol-related and emotional cues in alcohol dependent subjects following a single dose of the opioid receptor modulator nalmefene. The study will be done in a cross over design with nalmefene versus placebo.

Description:

All subjects will undergo a battery of minimal risk procedures during each study visit; filling out questionnaires, performing agreed behavioral tasks, scanning procedures including two functional MRI (fMRI) scans as well as structural MRI.

The fMRI will be obtained in non-abstinent participants with breath alcohol concentrations not larger than > 0.3 ‰ and withdrawal severity not more than 4 on the clinical institute withdrawal assessment for alcohol (CIWA-Ar) scale.

Alcohol consumption will be assessed with the Form90 interview. Severity of alcohol dependence will be examined with the Alcohol Dependence Scale (ADS). Drinking situations will be assessed with the Inventory of Drinking Situations (IDS). Trait aspects of craving for alcohol will be measured with the Obsessive Compulsive Drinking Scale (OCDS). To examine state and trait anxiety the State-Trait Anxiety Inventory (STAI) will be used. Depressive symptoms will be measured with the Beck Depression Inventory (BDI) and the State-Trait Depression Scales (STDS). Nicotine consumption will be assessed with the Fagerström Test for Nicotine Dependence.

The following scales will be administered before and after each fMRI scanning: The Alcohol Craving Questionnaire (ACQ), the Alcohol Urge Questionaire (AUQ) and visual analogue scales for craving assessment.

Participants will undergo two fMRI scanning sessions at intervals of one week: one 2 h after administration of nalmefene and one 2 h after administration of placebo, carried out in a randomized order.

MRI examinations include

• a cue-reactivity task;

• an emotional faces task;

• resting-state fMRI;

• structural MRI;

• including preparation, instructions and breaks

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• severe alcohol use disorder according to DSM 5 and "heavy drinking": alcohol consumption >=60g (men) and >=40g (women) (minimum of 5 days / week)

• right-handedness

• normal or corrected to normal vision

• signed written informed consent

Exclusion Criteria:

valid at the time of MRI investigation:

• psychotropic medication within the last 14 days

• severe withdrawal symptoms (CIWA-Ar > 4; Sullivan et al. 1989)

• intoxication (breath alcohol concentration > 0.3 ‰)

• common exclusion criteria for MRI (e.g. metal, claustrophobia)

• positive drug screening (opioids, cannabinoids, benzodiazepines, barbiturates, cocaine, amphetamines)

• pregnancy

• contraindications to the prescription of nalmefene valid at inclusion:

• previous severe withdrawal / withdrawal complications

• previous inpatient detoxification treatment

• other Axis I psychiatric diagnoses than alcohol- or nicotine-dependence in the last 12 months

• neurological disorders, history of brain injury

Related Conditions & MeSH terms

• Alcoholism

Intervention

Drug:
• Nalmefene
18mg of Nalmefen will be administered orally
• Placebo
Placebo tablet

Locations

Country	Name	City	State
Germany	Zentralinstitut für Seelische Gesundheit	Mannheim

Sponsors (2)

Lead Sponsor	Collaborator
Central Institute of Mental Health, Mannheim	Lundbeck GmbH, Ericusspitze 2, 20457 Hamburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in cue-induced brain activation between two fMRI scans (randomization to an intake of nalmefene (18 mg) or placebo).	This difference will be extracted from whole-brain contrast images in the VS and DS using the percentage of activated voxels in these regions of interest (ROI).	Primary outcome measures will be assessed on day 2 and day3 after fMRI scan, data collection will take up to 12 months