Using Exercise to Enhance Fear Extinction Learning

April 20, 2026 updated by: Josh Cisler

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: High-Intensity Exercise
High intensity exercise on a seated cycle for 26 minutes
Behavioral: Exercise
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.
Experimental: Moderate-Intensity Exercise
moderate intensity exercise on a seated cycle for 26 minutes
Behavioral: Exercise
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.
Experimental: Light-Intensity Exercise
Light intensity exercise on a seated cycle for 26 minutes
Behavioral: Exercise
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.
No Intervention: Quiet Rest

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
skin conductance response is a measure of sympathetic arousal and is measured on the palms using BIOPAC equipment
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.
blood oxygen level dependent (BOLD) response measured during fMRI provides an assessment of neural activity
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Josh Cisler

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Mental Health (NIMH)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 2, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 14, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 23, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY00006895
  • R01MH137445 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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