Fear and Avoidance in PTSD Patients

Post Traumatic Stress Disorder Clinical Trial

Official title:

Neural Correlates of Active Avoidance Learning and Their Interactions With Fear Extinction Mechanisms in PTSD Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04770584
• Other study ID #: 20-01675
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2021
• Est. completion date: January 2026

Study information

• Verified date: January 2023
• Source: NYU Langone Health
• Contact: Mohammed Milad, MD
• Phone: 646-754-7406
• Email: Mohammed.milad[@]nyulangone.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to study how the brain learn to avoid certain stimuli or situations using an experimental paradigm. The big goal is to measure brain responses and subject's feelings and expectations when they are learning to actively avoid experimental stimuli, and how fear extinction learning and monetary cost can change how and when subjects are to avoid.

Description:

This study aims to study the neural correlates of avoidance learning using a recently validated conditioning and active avoidance paradigm (CAAP). The overarching objective is to measure the neural correlates of active avoidance, and how fear extinction learning and monetary cost modulate these avoidance responses. Participants will include trauma-exposed healthy controls (TEHC), and participants with post-traumatic stress disorder (PTSD). Avoidance is common and often hinders the progression and success of extinction-based exposure therapy in PTSD. The data to be gathered in this study will enable us to probe neural mechanisms of avoidance, extinction, and decision-making to avoid or not, in addition to understanding the impact of cost on avoidance decision-making. These data will provide a more integrated platform for the understanding of the mechanisms of avoidance in both trauma-exposed healthy controls and PTSD psychopathology, which has important implications for treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. 18 - 70 years of age

2. Female or Male

3. Inclusion Criteria: PTSD Subjects

a. Diagnosis of current PTSD (as determined by CAPS, and primary diagnosis of PTSD as determined by SCID assessment of comorbidity)

4. Inclusion Criteria: Trauma-exposed healthy controls (TEHC)

1. SCID diagnosis consistent with no current or past history of Axis I psychiatric disorders, and no current or past history of PTSD (as determined by the CAPS).

2. History of trauma exposure.

5. Willing and able to provide informed consent.

Exclusion Criteria for ALL subjects:

1. History of neurologic disease (e.g. tic disorder)

2. Current suicidal ideation, plan or intent or suicidal behavior in past 6 months based on CSSRS or Self-injurious behavior that involves suicidal intent, requires medical attention, or occurs daily

3. History of seizure or significant head trauma (i.e., extended loss of consciousness, neurological sequelae, or known structural brain lesion)

4. History of the following Axis I psychiatric diagnosis: psychotic disorder, bipolar disorder, current eating disorder, or current or early remission substance abuse disorder.

5. Use of psychotropic medication within 4 weeks prior to study (within 6 weeks for fluoxetine, or other long-lived compounds; within one year for neuroleptics).

6. Current substance use (assessed by urine toxicology; positive urine toxicology screen for any substance, with the exception of THC).

7. Pregnancy (to be ruled out by urine ß-HCG).

8. Metallic implants or devices contraindicating magnetic resonance imaging.

Additional exclusion criteria for Trauma-exposed healthy controls (TEHC) group:

9. History of Axis I psychiatric diagnosis (current/past); (e.g., substance use disorder, eating disorder, mood disorders, anxiety disorders, OCD, PTSD).

Related Conditions & MeSH terms

• Post Traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Other:
• Fear Conditioning
Participants will be administered increasing intensities of mild electric shock via electrodes connected to the foot. New Biopac stimulators that can deliver higher shock intensity, provided participants agreement will be used to assure adequate conditioning levels. Stimulation is measures in milliamps (mA), and each delivered stimulation will be 0.5 seconds long (500 milliseconds). To colored (blue, red, & yellow) light stimuli (CS). The light stimulus is followed by a shock or no shock depending on color (blue & red - shock; yellow - no shock).
• Avoidance conditioning
Via button pressing. Only one stimulus-CS (i.e. blue colored light) will enable control over experiencing the shock: the participant can press the button during the first 2 seconds of the light presentation to avoid the shock. CS stays on for 6 seconds after the button is pressed. If the button is pressed, no shock will be administered. After 6 seconds, the light ends and the relief epoch ('good feeling') begins. Pressing the button to the other CS (i.e. red colored light) will not prevent the shock from occurring- the participant will still receive the mild shocked at CS offset (after 6 seconds). The third CS (i.e. yellow light) will serve as a control CS, so while the button is available, pressing it or not is of no consequence.
• Pavlovian fear extinction learning
After avoidance conditioning, the CS+ associated with avoidance responding (i.e. blue light) appears with no button to press and no shock is administered.
• Willingness to pay to avoid shock
On the next day, participants receive a monetary stipend to use to pay to guarantee that they are not to receive any shocks if they press a button from the CS+. No shocks will be delivered on day 2, regardless of money paid. This and all previously described experimental phases noted above will occur inside of the fMRI scanner.

Locations

Country	Name	City	State
United States	NYU Langone Health	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
NYU Langone Health	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Skin Conductance Response (SCR) of PTSD participants and Trauma-Exposed Healthy Controls	Skin Conductance Response will be collected from subjects during the entire course of the experiment, inside or outside of the fMRI scanner, to measure stress/sweat level. SCR is used by many psychological experiments to measure the participants stress/sweat, or level of anxiety in a particular moment, or in response to a specific cue.	Experimental Day 1, Experimental Day 2
Primary	Comparison of fMRI data of PTSD participants and Trauma-Exposed Healthy Controls	Participants will undergo a 3T MRI scan during the both experimental. All standard sequences and RF coils which we intend to use at the Center for Brain Imaging are FDA certified.fMRI data will be collected from subjects during the entire course of the 2-day experiment inside the fMRI scanner. fMRI data, including blood-oxygen-level-dependent (BOLD) responses, is used in neuroimaging studies assess neural correlate activations and observe the increase/decrease in activation of a particular brain area in response to a specific cue.	Experimental Day 1, Experimental Day 2
Secondary	Change in Anxiety	State-Trait Anxiety Inventory STAI (State) The State-Trait Anxiety Inventory (STAI) is a psychological inventory based on a 4-point Likert scale and consists of 40 questions on a self-report basis. The STAI measures two types of anxiety - state anxiety, or anxiety about an event, and trait anxiety, or anxiety level as a personal characteristic.	Experimental Day 1, Experimental Day 2
Secondary	Change in Emotional Stress tolerance	Distress Tolerance Scale (DTS) is a 15 item self-report measure of emotional distress tolerance. Individuals select on a 1-5 likert scale. (Strongly Disagree, Mildly Disagree, Feel Neutral, Mildly Agree, Strongly Agree) about each of the 16 statements about distress.	Experimental Day 1, Experimental Day 2
Secondary	Change in shock expectancy	Shock expectancy questionnaire is a self reported questionnaire that measures what they expect to see certain colors and whether they expected to feel shocks in the study.	Experimental Day 1, Experimental Day 2
Secondary	Ratings of Pleasantness in Conditioned Stimuli and Unconditioned Stimulus	Pleasantness Rating of relief scale measures participants sense of the relief they felt when no shock was given, on a scale from 1 to 5 (1=neutral, 5=extremely pleasant)	Experimental Day 1, Experimental Day 2
Secondary	Ratings of Unpleasantness in Conditioned Stimuli and Unconditioned Stimulus	Rating of Conditioned Stimuli(CS) and Unconditioned Stimulus (US) Unpleasantness measures participants sense of the unpleasantness they felt when the CS was given, on a scale from 1 to 5 (1=neutral, 5=extremely pleasant)	Experimental Day 1, Experimental Day 2