Ignite Creation Date:
2024-05-06 @ 4:00 AM
Last Modification Date:
2024-10-26 @ 11:42 AM
Study NCT ID:
NCT02438969
Status:
COMPLETED
Last Update Posted:
2024-04-02
First Post:
2015-05-05
Brief Title:
Epi-Genetic Modulators of Fear Extinction in Alcohol Dependence
Sponsor:
National Institute on Alcohol Abuse and Alcoholism NIAAA
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
EpiGenetic Modulators of Fear Extinction in Alcohol Dependence
Status:
COMPLETED
Status Verified Date:
2024-03-29
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
- Researchers want to learn if people with alcohol dependence have more difficulty learning to feel calm or learn to fear things more easily They also want to study how early life stress ELS affects the ability to learn to feel calm
Objective
- To see if people with alcohol dependence andor ELS have a harder time learning to feel calm than people without these Also to see if DNA is changed by ELS and if this change affects fear conditioning and extinction
Eligibility
Adults ages 21-65 with and without an alcohol use disorder AUD and with and without ELS
Healthy volunteers
Design
Participants will be screened with
Medical history
Physical exam
Blood and urine tests
Psychological tests
Treatment for symptoms of alcohol withdrawal if needed
Healthy volunteers will have 1 overnight visit 2 days 1 night AUD participants will stay at the clinic for about 4 weeks
Participants will
Rate alcohol usecraving depression anxiety and childhood trauma
Have psychophysiological measures electrodes and mild electric shock
Have a functional magnetic resonance imaging MRI scan Participants will lie on a table in a metal cylinder with a coil over their head In the first scanning session they will see pictures do a simple task and may get shocks Participants will also do a second scanning session in which they will perform the aforementioned fear conditioning and extinction task as well as a facial expression matching task an affective word processing task and a task measuring valuation of monetary rewards
Answer questions about their emotions some participants
Have blood drawn from an arm vein or intravenous IV line
AUD participants will get a dexamethasone pill The next day they will get a hormone injected in and have blood drawn from an IV line
AUD participants will have 3 follow-up visits with questions and blood and lab tests
- Researchers want to learn if people with alcohol dependence have more difficulty learning to feel calm or learn to fear things more easily They also want to study how early life stress ELS affects the ability to learn to feel calm
Objective
- To see if people with alcohol dependence andor ELS have a harder time learning to feel calm than people without these Also to see if DNA is changed by ELS and if this change affects fear conditioning and extinction
Eligibility
Adults ages 21-65 with and without an alcohol use disorder AUD and with and without ELS
Healthy volunteers
Design
Participants will be screened with
Medical history
Physical exam
Blood and urine tests
Psychological tests
Treatment for symptoms of alcohol withdrawal if needed
Healthy volunteers will have 1 overnight visit 2 days 1 night AUD participants will stay at the clinic for about 4 weeks
Participants will
Rate alcohol usecraving depression anxiety and childhood trauma
Have psychophysiological measures electrodes and mild electric shock
Have a functional magnetic resonance imaging MRI scan Participants will lie on a table in a metal cylinder with a coil over their head In the first scanning session they will see pictures do a simple task and may get shocks Participants will also do a second scanning session in which they will perform the aforementioned fear conditioning and extinction task as well as a facial expression matching task an affective word processing task and a task measuring valuation of monetary rewards
Answer questions about their emotions some participants
Have blood drawn from an arm vein or intravenous IV line
AUD participants will get a dexamethasone pill The next day they will get a hormone injected in and have blood drawn from an IV line
AUD participants will have 3 follow-up visits with questions and blood and lab tests
Detailed Description:
Objective
The primary goal of this study is to evaluate the role and interaction of epigenetic factors early life stress ELS exposure and alcohol use disorder AUD on neuronal mechanisms of fear conditioning and extinction
The central hypothesis is that participants with AUD and ELS will have disrupted fear extinction and in addition those with ELS will also have disrupted fear extinction AUD with ELS will have the most severe disruption of fear extinction as observed clinically in alcoholics with severe trauma - often presenting with the most severe phenotypes and being most treatment resistant A disruption in fear extinction or living in constant fear after stresstrauma could thus put the individual at risk for AUD
Identification and characterization of the neurobiological correlates underlying this mechanism is thus essential and could provide new avenues for treatment of AUD namely developing interventions that normalize abnormal fear extinctions These interventions could be for example cognitive-behavior based or molecular by targeting geneticepigenetic pathways potentially identified
Our proposal if successful will first establish a reliable measureable endophenotype of fear extinction in AUDELS both behaviorally skin conductance response and neuronal using an fMRI paradigm Furthermore we will carry out exploratory genetic and epigenetics studies that might influence these measures This model can then be used in follow up studies for novel therapeutic interventions that could target treatment of these mechanisms in AUD
Study Population
The study sample includes two patient groups and two control groups
1 treatment-seeking or non-treatment-seeking individuals with AUD and ELS exposure
2 treatment-seeking or non-treatment-seeking individuals with AUD without ELS exposure
3 healthy volunteers with ELS exposure
4 healthy volunteers without ELS exposure
Target accrual for each of these groups is 25
Design
Subjects will be evaluated for fear conditioning and extinction using shock conditioning extinction procedure combined with fMRI imaging that utilizes galvanic skin response All participants will undergo whole-genome methylome analyses to assess genome wide methylation patterns Genotyping of variants in candidate genes implicated in the biology of fear conditioningextinction will be carried out
Outcome Parameters
The primary outcome of interest is fear extinction measured by fMRI paradigms Secondary objectives include 1 explore the role of genetic variants and epigenetic factors and their impact on fear extinction in AUD and healthy controls with or without ELS 2 explore differences in reward processing and emotion processing measured by fMRI as a function of AUD ELS and epigenetic modulators and 3 examine the relationship between fear extinction and clinical outcomes in both AUD and ELS participants sample
The primary goal of this study is to evaluate the role and interaction of epigenetic factors early life stress ELS exposure and alcohol use disorder AUD on neuronal mechanisms of fear conditioning and extinction
The central hypothesis is that participants with AUD and ELS will have disrupted fear extinction and in addition those with ELS will also have disrupted fear extinction AUD with ELS will have the most severe disruption of fear extinction as observed clinically in alcoholics with severe trauma - often presenting with the most severe phenotypes and being most treatment resistant A disruption in fear extinction or living in constant fear after stresstrauma could thus put the individual at risk for AUD
Identification and characterization of the neurobiological correlates underlying this mechanism is thus essential and could provide new avenues for treatment of AUD namely developing interventions that normalize abnormal fear extinctions These interventions could be for example cognitive-behavior based or molecular by targeting geneticepigenetic pathways potentially identified
Our proposal if successful will first establish a reliable measureable endophenotype of fear extinction in AUDELS both behaviorally skin conductance response and neuronal using an fMRI paradigm Furthermore we will carry out exploratory genetic and epigenetics studies that might influence these measures This model can then be used in follow up studies for novel therapeutic interventions that could target treatment of these mechanisms in AUD
Study Population
The study sample includes two patient groups and two control groups
1 treatment-seeking or non-treatment-seeking individuals with AUD and ELS exposure
2 treatment-seeking or non-treatment-seeking individuals with AUD without ELS exposure
3 healthy volunteers with ELS exposure
4 healthy volunteers without ELS exposure
Target accrual for each of these groups is 25
Design
Subjects will be evaluated for fear conditioning and extinction using shock conditioning extinction procedure combined with fMRI imaging that utilizes galvanic skin response All participants will undergo whole-genome methylome analyses to assess genome wide methylation patterns Genotyping of variants in candidate genes implicated in the biology of fear conditioningextinction will be carried out
Outcome Parameters
The primary outcome of interest is fear extinction measured by fMRI paradigms Secondary objectives include 1 explore the role of genetic variants and epigenetic factors and their impact on fear extinction in AUD and healthy controls with or without ELS 2 explore differences in reward processing and emotion processing measured by fMRI as a function of AUD ELS and epigenetic modulators and 3 examine the relationship between fear extinction and clinical outcomes in both AUD and ELS participants sample
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 15-AA-0127 | None | None | None |