Fear and Avoidance in PTSD Patients

NCT ID: NCT04770584

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-09
• Study Completion Date: 2027-01-31

Brief Summary

The purpose of this research study is to study how the brain learns 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.

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 healthy controls (HC), 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.

Conditions

Post Traumatic Stress Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Emotional learning paradigm

After the initial screening / baseline assessment visit, participants will undergo two Experimental Visits, which include 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.

Group Type: EXPERIMENTAL

Fear Conditioning

Intervention Type: BEHAVIORAL

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.

Avoidance conditioning

Intervention Type: OTHER

Via button pressing. Only one stimulus-CS 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.

Pavlovian fear extinction learning

Intervention Type: OTHER

After avoidance conditioning, the CS+ associated with avoidance responding appears with no button to press and no shock is administered.

Willingness to pay to avoid shock

Intervention Type: OTHER

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+. This and all previously described experimental phases noted above will occur inside of the fMRI scanner.

Interventions

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.

Intervention Type: BEHAVIORAL

Avoidance conditioning

Via button pressing. Only one stimulus-CS 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.

Intervention Type: OTHER

Pavlovian fear extinction learning

After avoidance conditioning, the CS+ associated with avoidance responding appears with no button to press and no shock is administered.

Intervention Type: 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+. This and all previously described experimental phases noted above will occur inside of the fMRI scanner.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. 18 - 70 years of age

2. Female or Male

a. Diagnosis of current PTSD

1. SCID diagnosis consistent with no current psychiatric disorders, and no current PTSD

2. History of trauma exposure

1. SCID diagnosis consistent with no current psychiatric disorders ("Axis I" disorders).

2. No history of trauma exposure

6. Willing and able to provide informed consent.

Exclusion Criteria

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

2. Current significant 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

4. History of the serious/significant psychiatric diagnosis ("Axis I" disorders)

5. Use of neuroleptics within one year prior to study

6. Current substance use (assessed by urine toxicology; positive urine toxicology screen for any substance, with the exception of THC). Per PI judgement and approval: if urine toxicology is positive for a substance, participant may be eligible to proceed with study provided their urine toxicology (or saliva test for THC) is negative at experimental visit(s)

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

8. Metallic implants or devices contraindicating magnetic resonance imaging

9. High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process

10. Current psychiatric diagnosis ("Axis I" diagnoses)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Mohammed Milad

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mohammed Milad, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at Houston (UTHealth Houston)

Locations

UTHealth Houston

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mohammed Milad, PhD

Role: CONTACT

Mohammed.R.Milad@uth.tmc.edu

713-486-2754

Isabel Moallem, PhD

Role: CONTACT

B.Isabel.Moallem@uth.tmc.edu

Facility Contacts

Mohammed R. Milad, PhD

Role: primary

Mohammed.R.Milad@uth.tmc.edu

Other Identifiers

R01MH123736

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-MS-23-0495

Identifier Type: -

Identifier Source: org_study_id