Post Traumatic Stress DisorderNCT04770584
Fear and Avoidance in PTSD Patients
A study testing Fear Conditioning, Avoidance conditioning and Pavlovian fear extinction learning in people with Post Traumatic Stress Disorder, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Post Traumatic Stress Disorder
- What is being tested?
- Fear Conditioning, Avoidance conditioning and Pavlovian fear extinction learning
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2021to Jan 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 - 70 years of age
- Female or Male
- Inclusion Criteria: PTSD Subjects
- Diagnosis of current PTSD
- Inclusion Criteria: Trauma-exposed healthy controls (TEHC)
- SCID diagnosis consistent with no current psychiatric disorders, and no current PTSD
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- History of trauma exposure
- Inclusion Criteria: Healthy controls (HC)
- SCID diagnosis consistent with no current psychiatric disorders ("Axis I" disorders).
- No history of trauma exposure
- Willing and able to provide informed consent.
Who cannot join
- History of neurologic disease (e.g. tic disorder)
- 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
- History of seizure or significant head trauma
- History of the serious/significant psychiatric diagnosis ("Axis I" disorders)
- Use of neuroleptics within one year prior to study
- 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)
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- Pregnancy (to be ruled out by urine ß-HCG)
- Metallic implants or devices contraindicating magnetic resonance imaging
- High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process
- Additional exclusion criteria for Trauma-exposed healthy controls (TEHC) group and Healthy controls (HC) group:
- Current psychiatric diagnosis ("Axis I" diagnoses)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UTHealth Houston
Houston, Texas, 77054
Mohammed R. Milad, PhD, Mohammed.R.Milad@uth.tmc.edu
About this study
Official title: Neural Correlates of Active Avoidance Learning and Their Interactions With Fear Extinction Mechanisms in PTSD Patients
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.
Read the 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
- Being tested
- Fear Conditioning, Avoidance conditioning, Pavlovian fear extinction learning, Willingness to pay to avoid shock
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fear ConditioningBehavioural
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 conditioningOther
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 learningOther
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 shockOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Emotional learning paradigm | Experimental | 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. Receives: Behavioral: Fear Conditioning; Other: Avoidance conditioning; Other: Pavlovian fear extinction learning; Other: Willingness to pay to avoid shock |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skin Conductance Response (SCR)
Skin Conductance Response (SCR) assesses the stress/seat level, or level of anxiety in a particular moment, or in response to a specific cue. SCR will be reported in microsiemens.
Measured: Experimental Day 1, Experimental Day 2
Functional MRI (fMRI) responses
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.
Measured: Experimental Day 1, Experimental Day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start9 Sep 2021
- Primary completionJan 2028 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Texas Health Science Center, Houston
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Mohammed Milad, The University of Texas Health Science Center, Houston
- Investigators
- Mohammed Milad, PhD, Principal investigator, The University of Texas Health Science Center at Houston (UTHealth Houston)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04770584
- Sponsor's protocol ID
- HSC-MS-23-0495
- Other IDs
- R01MH123736
- Status last verified
- Apr 2026
- First submitted
- 22 Feb 2021
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Correlates of Active Avoidance Learning and Their Interactions With Fear Extinction Mechanisms in PTSD Patients
- ClinicalTrials.gov ID
- NCT04770584
- Acronym / sponsor ID
- HSC-MS-23-0495
- Conditions
- Post Traumatic Stress Disorder
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 9 Sep 2021 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 25 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Emotional learning paradigm | Experimental | Behavioral: Fear Conditioning, Other: Avoidance conditioning, Other: Pavlovian fear extinction learning, Other: Willingness to pay to avoid shockAfter 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 18 - 70 years of age
- Female or Male
- Inclusion Criteria: PTSD Subjects
- Inclusion Criteria: Trauma-exposed healthy controls (TEHC)
- Inclusion Criteria: Healthy controls (HC)
Key exclusion criteria (11 listed)
- History of neurologic disease (e.g. tic disorder)
- 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
- History of seizure or significant head trauma
- History of the serious/significant psychiatric diagnosis ("Axis I" disorders)
- Use of neuroleptics within one year prior to study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fear ConditioningParticipants 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. | Behavioural | Emotional learning paradigm |
| Avoidance conditioningVia 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. | Other | Emotional learning paradigm |
| Pavlovian fear extinction learningAfter avoidance conditioning, the CS+ associated with avoidance responding appears with no button to press and no shock is administered. | Other | Emotional learning paradigm |
| Willingness to pay to avoid shockOn 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. | Other | Emotional learning paradigm |
Primary outcome
Skin Conductance Response (SCR)
Time frame: Experimental Day 1, Experimental Day 2
Skin Conductance Response (SCR) assesses the stress/seat level, or level of anxiety in a particular moment, or in response to a specific cue. SCR will be reported in microsiemens.
Functional MRI (fMRI) responses
Time frame: Experimental Day 1, Experimental Day 2
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mohammed Milad, PhD principal investigator
The University of Texas Health Science Center at Houston (UTHealth Houston)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fear Conditioning, Avoidance conditioning and Pavlovian fear extinction learning in people with Post Traumatic Stress Disorder, run by The University of Texas Health Science Center, Houston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohammed Milad, PhD (713-486-2754, Mohammed.R.Milad@uth.tmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Skin Conductance Response (SCR) (time frame: Experimental Day 1, Experimental Day 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.