Clinical trial NCT02372318: Single-dose of Nalmefene to Modulate Neural Alcohol Cue Reactivity
Official title: Nalmefene Challenge to Modulate Neural Reactivity to Alcohol-related and Emotional Cues in Non-treatment Seeking Alcohol Dependent Participants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Alcoholism
Keywords: opiod receptor modulator nalmefene
cue-reactivity
fMRI
resting-state networks
Lead sponsor: Central Institute of Mental Health, Mannheim
Sponsor class: OTHER
Collaborators: name: Lundbeck GmbH, Ericusspitze 2, 20457 Hamburg
First posted: 2015-02-26
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Difference in cue-induced brain activation between two fMRI scans (randomization to an intake of nalmefene (18 mg) or placebo).
timeFrame: Primary outcome measures will be assessed on day 2 and day3 after fMRI scan, data collection will take up to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Zentralinstitut für Seelische Gesundheit
Study officials:
affiliation: Central Institute of Mental Health, Mannheim
name: Sabine Vollstädt-Klein, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Central Institute of Mental Health, Mannheim
name: Falk Kiefer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grundinger N, Gerhardt S, Karl D, Mann K, Kiefer F, Vollstadt-Klein S. The effects of nalmefene on the impulsive and reflective system in alcohol use disorder: A resting-state fMRI study. Psychopharmacology (Berl). 2022 Aug;239(8):2471-2489. doi: 10.1007/s00213-022-06137-1. Epub 2022 Apr 15.