Clinical trial NCT06866379: Involvement of the Septal Nuclei of the Human Brain in Alcohol Use Disorder
Official title: Involvement of the Septal Nuclei of the Human Brain in Alcohol Use Disorder - a Functional Magnetic Resonance Imaging Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alcohol Use Disorder
Keywords: Alcohol use disorder
AUD
septum
fMRI
Brain imaging
Lead sponsor: Psychiatric Centre Rigshospitalet
Sponsor class: OTHER
Collaborators: name: Neurobiology Research Unit, Rigshospitalet
name: The foundation of Mr. Ivan Nielsen
name: King Christian X foundation
First posted: 2025-03-10
Enrollment: 25
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Alcohol activates reward systems in different brain areas, i.e., the nucleus accumbens, dorsal striatum, extended amygdala, and prefrontal cortex. These areas are all part of the reward neurocircuitry, which plays an important role in the development of addiction.

A former study performed on rodents has shown that a specific area of the forebrain, the septal nuclei, is associated with the feeling of reward and, hence, addiction when stimulated. However, whether the septal area is involved in reward and addiction in humans is sparsely investigated.

The purpose of this brain-imaging study is to assess how the septal nuclei react to alcohol-related pictures shown to participants diagnosed with alcohol use disorder while lying in an MRI scanner, compared to people without a diagnosis of alcohol use disorder. This might give us a better understanding of how the septal nuclei is involved in reward and addiction.

Detailed description: This is a comparative, non-interventional, case-control, brain imaging study using the ALCUE paradigm to investigate the neuro-anatomical underpinings of AUD during a fMRI-scan. The contrast used for the fMRI scans is the BOLD signal which measures the ratio of oxygenated to deoxygenated blood in the brain as a measurement of neural activity.

The study will conclude after the last participant with AUD succesfully has undergone the fMRI scan, and will include 50 participants in total: 25 participants diagnosed with AUD and 25 participants without AUD (data from a previous brain imaging study). Written informed consent will be collected, before any trial activities are performed.

Eligibility criteria: Inclusion criteria:

* Diagnosed with alcohol use disorder (AUD) according to DSM-5, and alcohol dependence according to ICD-10
* An Alcohol Use Disorder Identification Test (AUDIT) score ≥ 15
* At least six heavy drinking days for the last 30 days, measured with the Time Line Follow Back (TLFB) method

Exclusion criteria:

* Diagnosis of schizophrenia spectrum disorder, paranoid psychosis, bipolar disorder, or mental retardation
* Previous or current substance use disorder other than AUD and nicotine use disorder
* History of alcohol withdrawal seizures within the past 5 years
* Alcohol withdrawal symptoms defined as a CIWA-Ar score \> 9 at screening or at the fMRI session
* Treatment with chlordiazepoxide or other benzodiazepine within the past 30 days
* Other pharmacological treatment for AUD within the past 30 days
* Treatment with GLP-1 analogues within the last 6 months
* Urine tests positive for psychoactive drugs (cocaine, amphetamine, TCH, methadone, opioids, and benzodiazepines) at screening
* DUDIT score ≥ 2/6 for females/males
* Contraindications for undergoing an fMRI scan (magnetic implants, metal splinters, pacemaker, claustrophobia, etc.)
* Females of childbearing potential who are either pregnant, breastfeeding or have the intention of becoming pregnant within the next month or are not using contraception appropriate for participating in a clinical study
* Pregnancy (positive urine pregnancy test)
* Unable to speak or understand Danish
* Any condition that the investigator feels would interfere with trial participation

Primary outcomes:
measure: Significant differences in alcohol cue related fMRI BOLD signals in the septal nuclei of the brain between AUD patients and healthy controls.
timeFrame: 12 minutes while the brain scan is being conducted
Secondary outcomes:
measure: Significant differences between AUD patients and healthy controls with respect to the subjectively reported craving degree
timeFrame: From beginning of the fMRI scan to the end of it at 12 minutes
measure: Significant differences between AUD patients and healthy controls with respect to alcohol cue related signals
timeFrame: From beginning of the fMRI scan to the end of it at 12 minutes
measure: Correlation between subjectively reported craving and BOLD signals
timeFrame: From beginning of the fMRI scan to the end of it at 12 minutes
Other outcomes:
Locations:
city: Frederiksberg
country: Denmark
facility: Psychiatric Center Copenhagen, Frederiksberg Hospital
Study officials:
References: