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Fear and Avoidance in PTSD Patients

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ClinicalTrials.gov Identifier: NCT04770584
Recruitment Status : Recruiting
First Posted : February 25, 2021
Last Update Posted : March 3, 2022
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
NYU Langone Health

Brief 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.

Condition or disease Intervention/treatment Phase
Post Traumatic Stress Disorder Other: Fear Conditioning Other: Avoidance conditioning Other: Pavlovian fear extinction learning Other: Willingness to pay to avoid shock Not Applicable

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Neural Correlates of Active Avoidance Learning and Their Interactions With Fear Extinction Mechanisms in PTSD Patients
Actual Study Start Date : July 1, 2021
Estimated Primary Completion Date : January 2026
Estimated Study Completion Date : January 2026

Arm Intervention/treatment
PTSD group
After the initial screening / baseline assessment visit, Post Traumatic Stress Disorder participants will undergo two Experimental Visits, which included participation in an emotional learning paradigm and an fMRI scan over the course of two consecutive days. Participants will be asked to look at pictures on a computer screen to measure physiological response physiological response (skin conductance response) and brain responses using a functional Magnetic Resonance Imaging (fMRI) machine. These two visits will be scheduled within a month from the baseline assessment visit.
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).

Other: 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.

Other: 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.

Other: 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.


Trauma-Exposed Healthy Controls (TEHC)
After the initial screening / baseline assessment visit, trauma-exposed healthy participants will undergo two Experimental Visits, which included participation in an emotional learning paradigm and an fMRI scan over the course of two consecutive days. Participants will be asked to look at pictures on a computer screen to measure physiological response physiological response (skin conductance response) and brain responses using a functional Magnetic Resonance Imaging (fMRI) machine. These two visits will be scheduled within a month from the baseline assessment visit.
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).

Other: 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.

Other: 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.

Other: 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.





Primary Outcome Measures :
  1. Comparison of Skin Conductance Response (SCR) of PTSD participants and Trauma-Exposed Healthy Controls [ Time Frame: Experimental Day 1, Experimental Day 2 ]
    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.

  2. Comparison of fMRI data of PTSD participants and Trauma-Exposed Healthy Controls [ Time Frame: Experimental Day 1, Experimental Day 2 ]
    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.


Secondary Outcome Measures :
  1. Change in Anxiety [ Time Frame: Experimental Day 1, Experimental Day 2 ]
    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.

  2. Change in Emotional Stress tolerance [ Time Frame: Experimental Day 1, Experimental Day 2 ]
    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.

  3. Change in shock expectancy [ Time Frame: Experimental Day 1, Experimental Day 2 ]
    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.

  4. Ratings of Pleasantness in Conditioned Stimuli and Unconditioned Stimulus [ Time Frame: Experimental Day 1, Experimental Day 2 ]
    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)

  5. Ratings of Unpleasantness in Conditioned Stimuli and Unconditioned Stimulus [ Time Frame: Experimental Day 1, Experimental Day 2 ]
    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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04770584


Contacts
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Contact: Mohammed Milad, MD 646-754-7406 Mohammed.milad@nyulangone.org
Contact: Noor Nassar 212-404-3850 noor.nassar@nyulangone.org

Locations
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United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Noor Nassar    212-404-3850    noor.nassar@nyulangone.org   
Principal Investigator: Mohammed R Milad, PhD         
Sponsors and Collaborators
NYU Langone Health
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Mohammed Milad NYU Langone
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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT04770584    
Other Study ID Numbers: 20-01675
First Posted: February 25, 2021    Key Record Dates
Last Update Posted: March 3, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
Access Criteria: The investigator who proposed to use the data will have access and give upon reasonable request. Requests should be directed to mohammed.milad@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders