Clinical trial NCT01097213: Neural Mechanisms Underlying Alcohol Induced Disinhibition
Official title: Collaboration on Alcohol Self Administration in Adolescents and Young Adults - Specific Aim 2: To Examine the Effect of Acute Alcohol Administration on Forebrain Disinhibition Using Functional Magnetic Resonance Imaging (fMRI)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alcoholism
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
Collaborators: name: Indiana University School of Medicine
First posted: 2010-04-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 19
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Residents living within 15 km (9.5 miles) from downtown Dresden

Brief summary: Forty 18-year-old social drinkers will be selected from the sample tested in specific aim 1 ("Prospective Assessment of Adolescent Drinking Trajectories With Computer-Assisted Self-administration of Ethanol (CASE)"; ClinicalTrials.gov identifier: NCT01063166). The functional magnetic resonance imaging blood-oxygen-level-dependent (fMRI BOLD) activity related to disinhibition measured with the Stop Signal task will be assessed during a continuous infusion of alcohol, clamping the arterial Breath Alcohol Concentration (aBAC) at 60 mg% for approximately one hour. It will be examined whether this fMRI BOLD activity is associated with the initial drinking trajectories and the alcohol consumption at age 18 and at age 20 identified in specific aim 1. Furthermore, fMRI will be used with the Taylor Aggression Paradigm to determine which brain areas mediate increased physical aggression during the same continuous infusion of alcohol as described above. All participants will undergo an alcohol and a placebo fMRI session.


Eligibility criteria: Inclusion Criteria:

* male and female Caucasian volunteers aged 18 years/0 months to 19 years/11 months;
* written informed consent by the subject;
* habitual social drinking during the two months preceding participation, defined by at least one drinking day in any two weeks-interval;
* at least one prior experience of alcohol intoxication
* being able to abstain from tobacco use for four hours without developing nicotine withdrawal symptoms;
* effective contraception in female participants;
* consenting to abstain from any illegal substance use for 2 weeks prior to participation;
* living within 15 km (9.5 miles) from downtown Dresden;
* sufficient information concerning alcohol use in both parents and in at least four second-degree relatives

Exclusion Criteria:

* prior medical treatment due to alcohol use;
* current or prior history of any serious disease, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, alcohol or drug dependence, but not alcohol abuse;
* current history of Axis-I psychiatric illness, including premenstrual dysphoric disorder;
* current or prior history of alcohol-induced flushing reactions;
* positive urine screen for cannabinoids, cocaine, amphetamines, opiates, or benzodiazepines;
* light or non-drinkers: averaging less than 2 standard drinks per week in the preceding two months;
* intention to become pregnant
* pregnancy or positive urine pregnancy screening or breast-feeding;
* any alcohol intake on the test day or the day before;
* use of medications known to interact with alcohol within 2 weeks of the study;
* positive hepatitis or HIV at screening, provided the subject consented to these tests
* any conditions posing safety issues with the fMRI scan, such as ferromagnetic implants, cardiac pacemakers or insulin pumps

Primary outcomes:
measure: Alcohol consumption
timeFrame: 2 years
Secondary outcomes:
measure: Absolute perfusion levels assessed with arterial spin labeling
timeFrame: 1 week
measure: Behavioural Stop Signal Reaction Time (SSRT)
timeFrame: 1 week
measure: BOLD fMRI correlate of aggression
timeFrame: 1 week
measure: Taylor aggression score
timeFrame: 1 week
measure: BOLD fMRI correlate of disinhibition
timeFrame: 1 week
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Technische Universitaet Dresden - Dresden fMRT-Neuroimaging Center
state: Saxony
Study officials:
affiliation: Technische Universitaet Dresden - - Faculty of Medicine Carl Gustav Carus - Department of Psychiatry and Psychotherapy
name: Michael N. Smolka, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitaetsklinikum Carl Gustav Carus at the Technische Universitaet Dresden
name: Ulrich S. Zimmermann, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gan G, Guevara A, Marxen M, Neumann M, Junger E, Kobiella A, Mennigen E, Pilhatsch M, Schwarz D, Zimmermann US, Smolka MN. Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex. Biol Psychiatry. 2014 Nov 1;76(9):698-707. doi: 10.1016/j.biopsych.2013.12.017. Epub 2014 Jan 15.