The objective of this study is to investigate the role of noradrenergic functioning in sex-specific dysregulation of the brain stress system in individuals with an AUD. This will be done by investigating sex differences in the acute effect of a α2a…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
psychische stoornissen, alcoholverslaving
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of this study is neural activation of the amygdala and
changes in amygdala-PFC connectivity in response to negative emotional picture
(compared to neutral pictures).
Secondary outcome
Secondary outcomes are i) neural activation of the amygdala and changes in
amygdala-PFC connectivity in response to alcohol-related cues (compared to
neutral cues), ii) alcohol and emotional cue-induced subjective responses
(craving and arousal) iii) resting heart-rate variability and iv) glutamate
concentrations in the dorsal anterior cingulate cortex (dACC) and v) resting
state connectivity
Background summary
Alcohol use disorder (AUD) is a leading risk factor for global disease burden.
Unfortunately, AUD treatment is only moderately successful. While the
prevalence of AUD is 2-3 times higher among men than women, this gap is quickly
closing. Nonetheless, women are structurally ignored in AUD research, impeding
the development of much-needed sex-tailored interventions. It has been
suggested that alcohol use and relapse in women is more strongly driven by
stress-related factors than in men with an AUD. More specifically, these sex
differences in stress-related alcohol use are thought to be mediated by the
noradrenergic mechanisms in the prefrontal cortex.
Study objective
The objective of this study is to investigate the role of noradrenergic
functioning in sex-specific dysregulation of the brain stress system in
individuals with an AUD. This will be done by investigating sex differences in
the acute effect of a α2a- noradrenergic receptor agonist (guanfacine) on
activation of the brain stress system in individuals with AUD, using task-based
pharmacological Magnetic Resonance Imaging (phMRI). It is hypothesized that
following a placebo, women compared to men with an AUD will show stronger
emotional cue-induced activation of the amygdala, and lower amygdala-PFC
connectivity. Guanfacine is expected to reduce emotional cue-induced activation
and strengthen cue-induced amygdala-PFC connectivity in women with an AUD more
so than it does in men.
Study design
Randomized, single blind, placebo controlled, cross-over phMRI study
Study burden and risks
Participants will need to come to the Spinoza Center twice, for a duration of 5
hours. These sessions will consist of an informed consent procedure (first
session only), the oral administration of guanfacine/placebo, continuous
measurement of heart-rate variability using an ambulatory monitoring system
(VU-AMS), the assessment of clinical and demographic information using an
online questionnaire (maximum duration of 60 minutes) and the actual phMRI scan
(45 minutes). During the time between the last questionnaire and start of the
phMRI study (approximately 3 hours), there will be no study procedures (except
for the continuous monitoring of HRV). In sum, participants will spend 2x 5
hours in the AMC (of which approximately 3 hours concern actual research time,
and the remaining hours consist of waiting time, needed for guanfacine to
achieve optimal blood plasma levels. The emotional cue-reactivity task that
will be used during the phMRI scan, makes use of standardized pictures from the
IAPS data set, which has been frequently used in research in both clinical and
non-clinical populations. No adverse side effects of this fMRI paradigm are
expected. Guanfacine has been used as a pharmacological challenge in various
studies, without adverse side effects, and is approved for the treatment of
children and adolescents with ADHD. Guanfacine can have an acute cardiovascular
effect (lowering heartrate), but especially the extended-release guanfacine is
associated with a relatively low side-effect profile. Hence the burden
associated with guanfacine administration is expected to be low. While the
participants themselves will not have direct beneficial effects of the study,
the knowledge resulting from this study has the potential to pave the way for
the development of sex-specific, pharmacological treatment options for alcohol
use disorder. The overall nature and extent of the added risk associated with
participation in the current study is to be classified as negligible and the
burden can be considered minimal.
van der boechorstraat 7
Amsterdam 1081 BT
NL
van der boechorstraat 7
Amsterdam 1081 BT
NL
Listed location countries
Age
Inclusion criteria
- Meeting at least 2 of the 11-DSM5 criteria for alcohol use disorder
- age 25-45
Exclusion criteria
- MRI contraindications
- having a cardiovascular disease
- the presence of cardiovascular risk factors (a history of sudden fainting
without reason, a relative that died as a consequence of heart failure before
the age of 60, a relative with pacemaker)
- heartrate < 60, systolic blood pressure < 120 on the day of testing
- the use of psychotropic medication (e.g., Ritalin, SSRI's, medication acting
on cardiovascular system; The use of CYP3A4-inductors and inhibitors)
- a history of neurological disorders
- for women: being pregnant, or breastfeeding
-
- An indication of a substance use disorder other than alcohol use disorder
based on the drug use disorder identification test (exclusion when score is
higher than 11)
- smoking more than 10 cigarettes per day
- a positive alcohol breath test on the day of testing
BMI < 18 or > 30
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL79897.018.21 |