PTSDNCT05368987
Neuromodulation of the Fear Extinction Circuit Using Temporally and Anatomically Specific TMS in Humans
A study testing Transcranial magnetic stimulation (TMS) and Fear Conditioning and Extinction Paradigm in people with PTSD, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial summary
This study aims to explore the mechanisms of how transcranial magnetic stimulation (TMS) impacts fear circuits. The overarching objectives are to understand how varying TMS parameters affect targeted brain regions in order to optimize its impact on enhancing fear extinction memory consolidation in a population with… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- PTSD
- What is being tested?
- Transcranial magnetic stimulation (TMS) and Fear Conditioning and Extinction Paradigm
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2022to 30 Sep 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
- Willing and able to provide informed consent.
- Inclusion Criteria for PTSD Subjects - Diagnosis of current PTSD
- Inclusion Criteria: Healthy Controls (HC) - no current psychiatric disorders ("Axis I" disorders)
Who cannot join
- Lifetime history of seizure or significant head trauma or other significant neurologic disease (e.g., tic disorder)
- History of serious/significant psychiatric diagnoses ("Axis I" diagnoses)
- Current significant suicidal ideation, plan or intent or suicidal behavior in past 6 months based on CSSRS and clinical judgment or Self-injurious behavior that involves suicidal intent, requires medical attention, or occurs daily
- Use of neuroleptics within one year prior to study
- Current substance use
- Pregnancy (to be ruled out by urine β-HCG).
Show all 11Show fewer
- Metallic implants or devices contraindicating magnetic resonance imaging.
- Currently taking medications that lower the seizure threshold. These include antipsychotics, high dose theophylline or stimulants such as methylphenidate. Patients taking bupropion must be on a stable dose (*last 3 months) and take less than or equal to 300 mg/day.
- Implanted devices in subject's head (shunts, cochlear implants); metal in subject's head (other than dental implants).
- 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 Healthy controls (HC) group: Current psychiatric diagnosis ("Axis I" diagnosis)
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, MD, Mohammed.R.Milad@uth.tmc.edu
About this study
This study aims to explore the mechanisms of how transcranial magnetic stimulation (TMS) impacts fear circuits. The overarching objectives are to understand how varying TMS parameters affect targeted brain regions in order to optimize its impact on enhancing fear extinction memory consolidation in a population with known fear extinction deficiencies: post-traumatic stress disorder (PTSD). 250 subjects will take part in this research study across UTHealth Houston. The study will include preliminary screenings, baseline visits, and experimental visits across four days
Read the detailed description
The experiments proposed are aimed to understand how timing and location of transcranial magnetic stimulation (TMS) in humans will impact their ability to reduce conditioned fear responses and impact the activation of their brain regions involved in fear regulation. The researchers will use a novel TMS approach to vary timing and location of its delivery so that the researchers can characterize and establish best time and location to obtain optimal impact on fear inhibition, and then test these parameters in PTSD patients and see if such can rescue extinction deficits in PTSD. The anticipated impact is to enhance our understanding of the neural mechanisms of associated with TMS use and explore potential novel approaches for advancing PTSD treatment.
- Conditions
- PTSD
- Being tested
- Transcranial magnetic stimulation (TMS), Fear Conditioning and Extinction Paradigm
- 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.
Transcranial magnetic stimulation (TMS)Device
Research subjects will undergo non-invasive TMS, with a frequency of 20Hz and intensity of 120% of their resting motor threshold (rMT) at varying time points and locations.
Fear Conditioning and Extinction ParadigmBehavioural
Participants will undergo a 3-day experimental paradigm. On day 1, participants will undergo a resting-state and structural scans in the fMRI scanner. The data from this scan will be used to determine the specific location of the TMS target for each participant. And participants will be aversively conditioned to two cues in the fMRI scanner. Task based and resting-state scans will occur on this day.
On day 2, subjects will undergo extinction training outside of the scanner where one of the conditioned cues will be paired with TMS in a temporally and anatomically specific manner. A resting-state scan will occur before and after inside the scanner.
On day 3, conditioned cues will be presented during the extinction recall phase of the study. This phase will be conducted in the fMRI scanner. Task-based and resting-state scans will occur on this day.
| Study group | Role | What they receive |
|---|---|---|
| Fear Conditioning and Extinction Paradigm, plus Transcranial Magnetic Stimulation (TMS) | Experimental | Participants will undergo a 3-day experimental paradigm. On day 1, participants will undergo a resting-state and structural scans in the fMRI scanner. The data from this scan will be used to determine the specific location of the TMS target for each participant. And participants will be aversively conditioned to two cues in the fMRI scanner. Task based and resting-state scans will occur on this day.
On day 2, subjects will undergo extinction training outside of the scanner where one of the conditioned cues will be paired with TMS in a temporally and anatomically specific manner. A resting-state scan will occur before and after inside the scanner.
On day 3, conditioned cues will be presented during the extinction recall phase of the study. This phase will be conducted in the fMRI scanner. Task-based and resting-state scans will occur on this day. Receives: Device: Transcranial magnetic stimulation (TMS); Behavioral: Fear Conditioning and Extinction Paradigm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skin Conductance Response (SCR)
Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.
Measured: Experimental Day 1
Skin Conductance Response (SCR)
Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.
Measured: Experimental Day 3
Functional MRI (fMRI) blood-oxygen-level-dependent (BOLD) 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. When these cells are active, there is an increase in blood oxygen in the surrounding area.
Measured: Experimental Day 1
Functional MRI (fMRI) blood-oxygen-level-dependent (BOLD) 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. When these cells are active, there is an increase in blood oxygen in the surrounding area.
Measured: Experimental Day 3
Secondary outcomes (2)
Score on State-Trait Anxiety Inventory (STAI) - Form Y1
STAI - Form Y1 is a commonly used measure of trait and state anxiety that consists of 20 statements that describe oneself. Each statement is scored from 1 (Not at all) to 4 (very much so). The total score range is 20-80. STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).
Measured: Experimental Day 1
Score on State-Trait Anxiety Inventory (STAI) - Form Y1
STAI - Form Y1 is a commonly used measure of trait and state anxiety that consists of 20 statements that describe oneself. Each statement is scored from 1 (Not at all) to 4 (very much so). The total score range is 20-80. STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).
Measured: Experimental Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2022
- Study start1 Feb 2022
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTSDStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- 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
- 250 participants (estimated)
Sponsor and investigators
- 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
- NCT05368987
- Sponsor's protocol ID
- HSC-MS-23-0426
- Other IDs
- R01MH125198
- Status last verified
- Apr 2026
- First submitted
- 5 May 2022
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- 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
- Neuromodulation of the Fear Extinction Circuit Using Temporally and Anatomically Specific TMS in Humans
- ClinicalTrials.gov ID
- NCT05368987
- Acronym / sponsor ID
- HSC-MS-23-0426
- Conditions
- PTSD
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 10 May 2022 (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.
This study aims to explore the mechanisms of how transcranial magnetic stimulation (TMS) impacts fear circuits. The overarching objectives are to understand how varying TMS parameters affect targeted brain regions in order to optimize its impact on enhancing fear extinction memory consolidation in a population with known fear extinction deficiencies: post-traumatic stress disorder (PTSD). 250 subjects will take part in this research study across UTHealth Houston. The study will include preliminary screenings, baseline visits, and experimental visits across four days
Detailed description
The experiments proposed are aimed to understand how timing and location of transcranial magnetic stimulation (TMS) in humans will impact their ability to reduce conditioned fear responses and impact the activation of their brain regions involved in fear regulation. The researchers will use a novel TMS approach to vary timing and location of its delivery so that the researchers can characterize and establish best time and location to obtain optimal impact on fear inhibition, and then test these parameters in PTSD patients and see if such can rescue extinction deficits in PTSD. The anticipated impact is to enhance our understanding of the neural mechanisms of associated with TMS use and explore potential novel approaches for advancing PTSD 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 |
|---|---|---|
| Fear Conditioning and Extinction Paradigm, plus Transcranial Magnetic Stimulation (TMS) | Experimental | Device: Transcranial magnetic stimulation (TMS), Behavioral: Fear Conditioning and Extinction ParadigmParticipants will undergo a 3-day experimental paradigm. On day 1, participants will undergo a resting-state and structural scans in the fMRI scanner. The data from this scan will be used to determine the specific location of the TMS target for each participant. And participants will be aversively conditioned to two cues in the fMRI scanner. Task based and resting-state scans will occur on this day. On day 2, subjects will undergo extinction training outside of the scanner where one of the conditioned cues will be paired with TMS in a temporally and anatomically specific manner. A resting-state scan will occur before and after inside the scanner. On day 3, conditioned cues will be presented during the extinction recall phase of the study. This phase will be conducted in the fMRI scanner. Task-based and resting-state scans will occur on this day. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Willing and able to provide informed consent.
- Inclusion Criteria for PTSD Subjects - Diagnosis of current PTSD
- Inclusion Criteria: Healthy Controls (HC) - no current psychiatric disorders ("Axis I" disorders)
Key exclusion criteria (11 listed)
- Lifetime history of seizure or significant head trauma or other significant neurologic disease (e.g., tic disorder)
- History of serious/significant psychiatric diagnoses ("Axis I" diagnoses)
- Current significant suicidal ideation, plan or intent or suicidal behavior in past 6 months based on CSSRS and clinical judgment or Self-injurious behavior that involves suicidal intent, requires medical attention, or occurs daily
- Use of neuroleptics within one year prior to study
- Current substance use
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 |
|---|---|---|
| Transcranial magnetic stimulation (TMS)Research subjects will undergo non-invasive TMS, with a frequency of 20Hz and intensity of 120% of their resting motor threshold (rMT) at varying time points and locations. | Device | Fear Conditioning and Extinction Paradigm, plus Transcranial Magnetic Stimulation (TMS) |
| Fear Conditioning and Extinction ParadigmParticipants will undergo a 3-day experimental paradigm. On day 1, participants will undergo a resting-state and structural scans in the fMRI scanner. The data from this scan will be used to determine the specific location of the TMS target for each participant. And participants will be aversively conditioned to two cues in the fMRI scanner. Task based and resting-state scans will occur on this day. On day 2, subjects will undergo extinction training outside of the scanner where one of the conditioned cues will be paired with TMS in a temporally and anatomically specific manner. A resting-state scan will occur before and after inside the scanner. On day 3, conditioned cues will be presented during the extinction recall phase of the study. This phase will be conducted in the fMRI scanner. Task-based and resting-state scans will occur on this day. | Behavioural | Fear Conditioning and Extinction Paradigm, plus Transcranial Magnetic Stimulation (TMS) |
Primary outcome
Skin Conductance Response (SCR)
Time frame: Experimental Day 1
Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.
Skin Conductance Response (SCR)
Time frame: Experimental Day 3
Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.
Functional MRI (fMRI) blood-oxygen-level-dependent (BOLD) responses
Time frame: Experimental Day 1
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. When these cells are active, there is an increase in blood oxygen in the surrounding area.
Functional MRI (fMRI) blood-oxygen-level-dependent (BOLD) responses
Time frame: Experimental Day 3
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. When these cells are active, there is an increase in blood oxygen in the surrounding area.
2 secondary outcomes
Score on State-Trait Anxiety Inventory (STAI) - Form Y1
Time frame: Experimental Day 1
Score on State-Trait Anxiety Inventory (STAI) - Form Y1
Time frame: Experimental Day 3
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 Transcranial magnetic stimulation (TMS) and Fear Conditioning and Extinction Paradigm in people with PTSD, 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 3 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). The study lists 4 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.