PTSDNCT07548125
Using Exercise to Enhance Fear Extinction Learning
A study testing Exercise in people with PTSD and Exercise Intensity, run by Josh Cisler at 1 site in United States.
Trial summary
The goal of the current project is to establish the efficacy and mechanisms of exercise-enhanced fear extinction retrieval and generalization in posttraumatic stress disorder (PTSD). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- PTSD, Exercise Intensity, Fear Extinction
- What is being tested?
- Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2025to 1 May 2030
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18 - 55 years of age
- Currently experiencing at least 4 PTSD symptoms with at least 1 re-experiencing symptom (e.g., trauma memory intrusion, trauma nightmares, trauma flashbacks, intense emotional distress related to trauma, or marked physiological reactivity related to trauma) from criterion B.
- English speaking
- Medically healthy
Who cannot join
- being pregnant
- having a history of light headedness or fainting during physical activity
- having a history of chest pain during physical activity
- having a bone, joint, cardiac, or other medical condition that a doctor has said may be worsened by physical activity
- responding 'Yes' to any of the seven questions on the Physical Activity Readiness Questionnaire (PAR-Q; unless they provide a doctor's note indicating that it is safe for them to engage in aerobic exercise )
- percutaneous coronary intervention or acute myocardial infarction in the last 6 weeks
Show all 21Show fewer
- unstable arrhythmias/implanted cardiac defibrillator shocks in the last 3 months
- Internal ferromagnetic objects (such as electronic devices, surgical implants, shrapnel, etc.)
- Nonremovable dental implants, such as braces or upper permanent retainers, as these will distort the MRI images we collect (note: filings, crowns, and silver or gold teeth are OK)
- Any other condition, medication, or implant that the investigator believes would degrade image quality or render data unusable
- psychotic disorders
- Permanent makeup or tattoos with metallic dyes,
- A self-reported history of loss of consciousness (greater than 30 minutes)
- physical disabilities that prohibit task performance (such as blindness or deafness)
- Any other condition that the investigator believes might put the participant at risk
- Claustrophobia
- History of cardiovascular disease
- on-going traumatic event exposure (e.g., living with an abusive partner)
- Severe substance use disorder.
- unstable medication (changes within the past ~4 weeks)
- Acute sedatives/pain killers (e.g., benzodiazepines, Vicodin) and prescription stimulants (e.g., Adderall) would not be permitted for 6 hours prior to the study visit.
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
Health Discovery Building
Austin, Texas, 78712
Josh M Cisler, PhD, 512-495-5162, josh.cisler@austin.utexas.edu
About this study
Official title: Efficacy and Mechanisms of Exercise-Enhanced Fear Extinction
The goal of the current project is to establish the efficacy and mechanisms of exercise-enhanced fear extinction retrieval and generalization in posttraumatic stress disorder (PTSD). Exposure therapy is the gold standard treatment for PTSD, yet is only associated with remission rates of ~55% and in clear need of improvement. Exposure therapy is hypothesized to work through mechanisms of fear extinction learning, and as such, laboratory-based fear extinction paradigms are widely used as models of exposure therapy. Recent data demonstrates that moderate-intensity aerobic exercise, delivered specifically during or after fear extinction learning, can boost the consolidation of fear extinction learning. Consistent with emerging models of exercise's pro-extinction effect, our pilot data among women with PTSD found that moderate intensity aerobic exercise delivered after fear extinction learning leads to a reduction in subsequent fear responding 24hrs later, an effect that was mediated by exercise-induced increases in peripheral brain derived neurotrophic factor (BDNF). Our pilot data using multivariate pattern analyses (MVPA) also identified divided neurocircuitry organization of fear vs safety memories, and that this divided neural organization was altered in PTSD. Building on our pilot data, the current project would 1) compare the impact of different intensities of exercise delivered following fear extinction learning on multimodal measures of fear extinction retrieval and generalization, 2) identify the impact of exercise on MVPA representations of fear vs safety memories, and 3) demonstrate that spontaneous reactivations of extinction encodings in the acute consolidation window operate as candidate mechanisms by which exercise enhances extinction retrieval and generalization. Using a 3-day fear conditioning, fear extinction, and fear extinction retrieval and recognition task during functional magnetic resonance imaging (fMRI), 200 adults with PTSD would be randomly assigned to either resting control or 30min of either light, moderate, or high intensity exercise. Testing dose-response relationships between exercise intensity and fear extinction will inform translation of this research to clinical settings. A one week-follow-up extinction retrieval test would investigate the impact of exercise on longer-term retention. This project would provide a critical evaluation of the impact of aerobic exercise on consolidation and recall of extinction learning in PTSD samples, thereby providing a strong foundation to translate this research to clinical care and enhance clinical outcomes for PTSD. The project would also provide general knowledge regarding dose-response relationships and neural mechanisms that support enhanced extinction, thereby informing development of additional novel treatments.
- Conditions
- PTSD, Exercise Intensity, Fear Extinction, Fear Conditioning
- Being tested
- Exercise
- 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.
ExerciseBehavioural
Exercise consists of a total duration of 26 minutes on a seated exercise cycle. Exercise begins with a 3min warm-up, 20min of exercise at the desired intensity range, and then a 3min cool-down. During exercise, heart rate is monitored and perceived effort is assessed every 2 minutes.
| Study group | Role | What they receive |
|---|---|---|
| High-Intensity Exercise | Experimental | High intensity exercise on a seated cycle for 26 minutes Receives: Behavioral: Exercise |
| Moderate-Intensity Exercise | Experimental | moderate intensity exercise on a seated cycle for 26 minutes Receives: Behavioral: Exercise |
| Light-Intensity Exercise | Experimental | Light intensity exercise on a seated cycle for 26 minutes Receives: Behavioral: Exercise |
| Quiet Rest | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Threat Expectation
Threat expectation is a cognitive process and measure of fear towards conditioned stimuli
Measured: Threat expectation to conditioned stimuli is measured with a 4pt Likert Scale (range 0-3) in response to conditioned stimuli, using self-report, as a measure of cognitive features of fear, one day after intervention and 7-13 days after intervention.
Secondary outcomes (2)
Skin Conductance Responses (SCRs)
skin conductance response is a measure of sympathetic arousal and is measured on the palms using BIOPAC equipment
Measured: SCR is assessed on the palms in response to conditioned stimuli, using BIOPAC equipment, as a measure of sympathetic arousal, one day after intervention and 7-13 days after intervention.
BOLD Activation to CS+ and CS-
blood oxygen level dependent (BOLD) response measured during fMRI provides an assessment of neural activity
Measured: BOLD activity to conditioned stimuli is measured during fMRI in response to conditioned stimuli, using 3T Siemens Prisma, as a measure of neural activity, one day after intervention and 7-13 days after intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2026
- Study start2 Sep 2025
- Primary completion1 May 2030 (estimated)
- Study completion1 May 2030 (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.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Josh Cisler
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Josh Cisler, University of Texas at Austin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07548125
- Sponsor's protocol ID
- STUDY00006895
- Other IDs
- R01MH137445
- Status last verified
- Apr 2026
- First submitted
- 14 Apr 2026
- Last updated
- 23 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Mechanisms of Exercise-Enhanced Fear Extinction
- ClinicalTrials.gov ID
- NCT07548125
- Acronym / sponsor ID
- STUDY00006895
- Conditions
- PTSD, Exercise Intensity, Fear Extinction, Fear Conditioning
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Josh CislerUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 2 Sep 2025 (actual)
- Primary completion
- 1 May 2030 (estimated)
- Study completion
- 1 May 2030 (estimated)
- First posted
- 23 Apr 2026 (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 goal of the current project is to establish the efficacy and mechanisms of exercise-enhanced fear extinction retrieval and generalization in posttraumatic stress disorder (PTSD). Exposure therapy is the gold standard treatment for PTSD, yet is only associated with remission rates of ~55% and in clear need of improvement. Exposure therapy is hypothesized to work through mechanisms of fear extinction learning, and as such, laboratory-based fear extinction paradigms are widely used as models of exposure therapy. Recent data demonstrates that moderate-intensity aerobic exercise, delivered specifically during or after fear extinction learning, can boost the consolidation of fear extinction learning. Consistent with emerging models of exercise's pro-extinction effect, our pilot data among women with PTSD found that moderate intensity aerobic exercise delivered after fear extinction learning leads to a reduction in subsequent fear responding 24hrs later, an effect that was mediated by exercise-induced increases in peripheral brain derived neurotrophic factor (BDNF). Our pilot data using multivariate pattern analyses (MVPA) also identified divided neurocircuitry organization of fear vs safety memories, and that this divided neural organization was altered in PTSD. Building on our pilot data, the current project would 1) compare the impact of different intensities of exercise delivered following fear extinction learning on multimodal measures of fear extinction retrieval and generalization, 2) identify the impact of exercise on MVPA representations of fear vs safety memories, and 3) demonstrate that spontaneous reactivations of extinction encodings in the acute consolidation window operate as candidate mechanisms by which exercise enhances extinction retrieval and generalization. Using a 3-day fear conditioning, fear extinction, and fear extinction retrieval and recognition task during functional magnetic resonance imaging (fMRI), 200 adults with PTSD would be randomly assigned to either resting control or 30min of either light, moderate, or high intensity exercise. Testing dose-response relationships between exercise intensity and fear extinction will inform translation of this research to clinical settings. A one week-follow-up extinction retrieval test would investigate the impact of exercise on longer-term retention. This project would provide a critical evaluation of the impact of aerobic exercise on consolidation and recall of extinction learning in PTSD samples, thereby providing a strong foundation to translate this research to clinical care and enhance clinical outcomes for PTSD. The project would also provide general knowledge regarding dose-response relationships and neural mechanisms that support enhanced extinction, thereby informing development of additional novel treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| High-Intensity Exercise | Experimental | Behavioral: ExerciseHigh intensity exercise on a seated cycle for 26 minutes |
| Moderate-Intensity Exercise | Experimental | Behavioral: Exercisemoderate intensity exercise on a seated cycle for 26 minutes |
| Light-Intensity Exercise | Experimental | Behavioral: ExerciseLight intensity exercise on a seated cycle for 26 minutes |
| Quiet Rest | No intervention | – |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age 18 - 55 years of age
- Currently experiencing at least 4 PTSD symptoms with at least 1 re-experiencing symptom (e.g., trauma memory intrusion, trauma nightmares, trauma flashbacks, intense emotional distress related to trauma, or marked physiological reactivity related to trauma) from criterion B.
- English speaking
- Medically healthy
Key exclusion criteria (21 listed)
- being pregnant
- having a history of light headedness or fainting during physical activity
- having a history of chest pain during physical activity
- having a bone, joint, cardiac, or other medical condition that a doctor has said may be worsened by physical activity
- responding 'Yes' to any of the seven questions on the Physical Activity Readiness Questionnaire (PAR-Q; unless they provide a doctor's note indicating that it is safe for them to engage in aerobic exercise )
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 |
|---|---|---|
| ExerciseExercise consists of a total duration of 26 minutes on a seated exercise cycle. Exercise begins with a 3min warm-up, 20min of exercise at the desired intensity range, and then a 3min cool-down. During exercise, heart rate is monitored and perceived effort is assessed every 2 minutes. | Behavioural | High-Intensity Exercise, Light-Intensity Exercise, Moderate-Intensity Exercise |
Primary outcome
Threat Expectation
Time frame: Threat expectation to conditioned stimuli is measured with a 4pt Likert Scale (range 0-3) in response to conditioned stimuli, using self-report, as a measure of cognitive features of fear, one day after intervention and 7-13 days after intervention.
Threat expectation is a cognitive process and measure of fear towards conditioned stimuli
2 secondary outcomes
Skin Conductance Responses (SCRs)
Time frame: SCR is assessed on the palms in response to conditioned stimuli, using BIOPAC equipment, as a measure of sympathetic arousal, one day after intervention and 7-13 days after intervention.
BOLD Activation to CS+ and CS-
Time frame: BOLD activity to conditioned stimuli is measured during fMRI in response to conditioned stimuli, using 3T Siemens Prisma, as a measure of neural activity, one day after intervention and 7-13 days after intervention.
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 23 Apr 2026.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise in people with PTSD and Exercise Intensity, run by Josh Cisler 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 4 inclusion and 21 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 23 Apr 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 Josh M Cisler, PhD (512-495-5162, josh.cisler@austin.utexas.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Threat Expectation (time frame: Threat expectation to conditioned stimuli is measured with a 4pt Likert Scale (range 0-3) in response to conditioned stimuli, using self-report, as a measure of cognitive features of fear, one day after intervention and 7-13 days after intervention.). 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 23 Apr 2026; AzTrials last refreshed its copy on 28 Oct 2026.