Single-dose of Nalmefene to Modulate Neural Alcohol Cue Reactivity (NALCUE)

Central Institute of Mental Health, Mannheim

Status and phase

Terminated

Early Phase 1

Conditions

Alcoholism

Treatments

Drug: Placebo

Drug: Nalmefene

Study type

Interventional

Funder types

Other

Identifiers

NCT02372318

Details and patient eligibility

About

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.

Full 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

Enrollment

23 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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