Post Traumatic Stress DisorderPERPPNCT06096740
Psychotherapy Effects on Reward Processing in PTSD
A study testing Cognitive Processing Therapy in people with Post Traumatic Stress Disorder and Diminished Pleasure, run by University of Texas at Austin at 1 site in United States.
Trial summary
The purpose of this study is to identify how trauma-focused psychotherapy changes the function of brain circuitry in posttraumatic stress disorder (PTSD) and how this mediates improvements in the diminished ability to experience positive emotions following a traumatic or extremely stressful life event. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post Traumatic Stress Disorder, Diminished Pleasure, Anhedonia
- What is being tested?
- Cognitive Processing Therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2024to 1 May 2029
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- English as primary language, and comprehension suitable to understand experimenter instructions.
- Current and chronic syndromic PTSD, defined as being exposed to a DSM-5 Criterion A traumatic event, with the presence DSM-5 qualifying PTSD symptoms for at least 3 months, as assessed by the Clinician-Administered PTSD Scale for DSM-5.
- Able and willing to undergo functional magnetic resonance imaging (fMRI).
- Willingness to participate in repeated assessments and as part of a delayed treatment group.
Who cannot join
- Evidence of current or prior history of psychosis or bipolar disorder as evidenced by self-report or clinical interview.
- Active substance dependence within the past 6 months as evidenced by clinical interview.
- Current regular psychiatric medication use (i.e. antidepressants), except for as-needed benzodiazepine or opiate medication no more than three times per week, on average, or for short-duration stimulant medication for attention deficit hyperactivity disorder that can be skipped within 24 hours of study visits.
- A recent (<6 months) suicide attempt or current active ideation with intent.
- Unremovable ferrous metal in body.
- History of neurological disorder, stroke, seizures/convulsions (except febrile seizures in childhood), epilepsy, brain surgery, electroconvulsive or radiation treatment, brain hemorrhage or tumor, or thyroid disorder.
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- Anyone who is pregnant or trying to become pregnant.
- Current or past year (> 3 sessions), psychotherapy with a prominent exposure or cognitive restructuring component.
- Previous or current (es)ketamine treatment and/ or brain stimulation/neuromodulation treatment.
- Other ongoing treatment that is likely to confound experimental effects.
- Previous penetrating head injury/traumatic brain injury. Mild-to-moderate traumatic brain injury without penetrating injury is allowable.
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 (HDB), 1601 Trinity St., Bldg B., Z0600
Austin, Texas, 78712
Lauren Enten, B.S.A., 512-495-5856, fonzolab@austin.utexas.edu
Greg Fonzo, Ph.D.
About this study
Official title: The Effects of Trauma-focused Psychotherapy on Reward Circuitry Function and Information Encoding
The purpose of this study is to identify how trauma-focused psychotherapy changes the function of brain circuitry in posttraumatic stress disorder (PTSD) and how this mediates improvements in the diminished ability to experience positive emotions following a traumatic or extremely stressful life event. In this instance, the investigators will be using cognitive processing therapy (CPT), a widely-utilized and evidence-based treatment for PTSD.
Read the detailed description
The goals of the study are as follows:
- Quantify, under conditions of safety (no threat), how PTSD psychotherapy alters reward circuit function and information encoding.
- Identify how presence of threat augments PTSD psychotherapy effects on reward circuit function and information encoding.
- (Exploratory). Identify how, following psychotherapy, changes in reward circuit function and information encoding under conditions of safety and threat are associated with improvements in symptoms of diminished positive affect (DimPA).
To accomplish the goals of the study, the investigators propose a neuroimaging-coupled, randomized clinical trial of immediate vs. delayed individual cognitive processing therapy (CPT) in individuals (N=120) with a primary diagnosis of chronic PTSD. Individuals will undergo, prior to randomization, clinical and neurobiological assessment with functional magnetic resonance imaging (fMRI) during completion of several reward processing paradigms. Two of these involve both a normal "safe" context and a threat context manipulation (threat of mild electrodermal shock that is periodically cycled throughout the task). Another paradigm involves making decisions to either approach reward or forego a reward when this decision conflicts with the likelihood of an aversive outcome. This is known as approach-avoidance conflict (AAC). This battery will provide a comprehensive characterization of reward processing behavior and circuit function and establish its relationship to treatment processes, as well as how such processes may vary as a function of threat.
- Conditions
- Post Traumatic Stress Disorder, Diminished Pleasure, Anhedonia, PTSD, Chronic PTSD, Chronic Post-Traumatic Stress Disorder
- Being tested
- Cognitive Processing Therapy
- Keywords
- PTSD, Post Traumatic Stress, Emotional Numbing, CPT, Cognitive Processing Therapy, Therapy, Chronic PTSD
- Medical subject headings
- Stress Disorders, Post-Traumatic, Anhedonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Processing TherapyBehavioural
Also called CPT
Cognitive processing therapy is a widely-utilized, empirically-supported treatment developed for PTSD. It is based on a cognitive theory of trauma which emphasizes the impact of trauma on belief systems and the development of "stuck points", which are unhealthy, unrealistic, and maladaptive ways of thinking that serve to maintain unhealthy beliefs and reinforce PTSD symptoms.
| Study group | Role | What they receive |
|---|---|---|
| Immediate Treatment | Experimental | Those individuals randomized to immediate treatment will commence individual cognitive processing therapy (CPT) with an assigned study therapist, following the completion of baseline procedures. Receives: Behavioral: Cognitive Processing Therapy |
| Delayed Treatment | Placebo comparator | Individuals randomized to the delayed treatment condition will be informed after randomization that their treatment will start in 6-8 weeks (the approximate period it will take for individuals in the immediate treatment arm to complete CPT and post-treatment assessments). Receives: Behavioral: Cognitive Processing Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Within subject beta coefficients for each parametrically modulated regressor of the Reinforcement Learning Task with Threat
The changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation associated with individual trial-by-trial reinforcement learning computational model parameters at the time of choice valuation (expected reward value during safe contexts and expected reward value during threat contexts) and choice outcome (reward prediction errors during safe contexts and reward prediction errors during threat contexts).
Measured: [10 weeks]
Secondary outcomes (3)
Within-subject BOLD contrast for unexpected absence of juice vs. expected absence of juice (negative temporal Prediction Errors) for safe and threat contexts.
The changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation between the unexpected absence of juice vs. expected absence of juice in safe contexts and threat contexts.
Measured: [10 weeks]
Within-subject BOLD contrast for the unexpected delivery of juice vs. the expected delivery of juice (positive temporal Prediction Errors) for safe and threat contexts.
The changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation between the unexpected delivery of juice vs. the expected delivery of juice in both safe and threat contexts.
Measured: [10 weeks]
Within subject beta coefficients for each parametrically modulated regressor of an approach avoidance conflict task.
The changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation associated with individual trial-by-trial reinforcement learning computational model parameters at the time of choice valuation (expected reward value, expected threat value, and conflict between reward and threat value), anticipation (expected reward and threat value), and choice outcome (reward and threat prediction errors).
Measured: [10 weeks]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2023
- Study start1 Jun 2024
- Primary completion1 Mar 2029 (estimated)
- Study completion1 May 2029 (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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomization will be stratified based upon baseline presence/absence of MDD and will occur using pre-specified block randomization with randomly-sized blocks of either 4 or 6 to ensure near-equal distribution of participants with and without comorbid MDD between the two arms over time, while avoiding the ability for study personnel to predict treatment assignment of the next participant. Blocks will involve various orderings of participant assignment, each block will be assigned a number, and a random list generator will then order the block sequences prior to the start of the study. This will ensure equal numbers of participants with and without MDD are assigned to each treatment condition and limit predictability of assignment.
- Masking
- Double blind
- Who is masked
- Care provider, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas at Austin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Greg Fonzo, University of Texas at Austin
- Investigators
- Gregory A Fonzo, PhD, Principal investigator, The University of Texas at Austin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06096740
- Sponsor's protocol ID
- STUDY00004746
- Acronym
- PERPP
- Status last verified
- Sep 2025
- First submitted
- 17 Oct 2023
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Trauma-focused Psychotherapy on Reward Circuitry Function and Information Encoding
- ClinicalTrials.gov ID
- NCT06096740
- Acronym / sponsor ID
- PERPP / STUDY00004746
- Conditions
- Post Traumatic Stress Disorder, Diminished Pleasure, Anhedonia, PTSD, Chronic PTSD, Chronic Post-Traumatic Stress Disorder
- Keywords
- PTSD, Post Traumatic Stress, Emotional Numbing, CPT, Cognitive Processing Therapy, Therapy, Chronic PTSD
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of Texas at AustinUniversity, hospital or other
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 1 Mar 2029 (estimated)
- Study completion
- 1 May 2029 (estimated)
- First posted
- 24 Oct 2023 (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 study is to identify how trauma-focused psychotherapy changes the function of brain circuitry in posttraumatic stress disorder (PTSD) and how this mediates improvements in the diminished ability to experience positive emotions following a traumatic or extremely stressful life event. In this instance, the investigators will be using cognitive processing therapy (CPT), a widely-utilized and evidence-based treatment for PTSD.
Detailed description
The goals of the study are as follows:
- Quantify, under conditions of safety (no threat), how PTSD psychotherapy alters reward circuit function and information encoding.
- Identify how presence of threat augments PTSD psychotherapy effects on reward circuit function and information encoding.
- (Exploratory). Identify how, following psychotherapy, changes in reward circuit function and information encoding under conditions of safety and threat are associated with improvements in symptoms of diminished positive affect (DimPA).
To accomplish the goals of the study, the investigators propose a neuroimaging-coupled, randomized clinical trial of immediate vs. delayed individual cognitive processing therapy (CPT) in individuals (N=120) with a primary diagnosis of chronic PTSD. Individuals will undergo, prior to randomization, clinical and neurobiological assessment with functional magnetic resonance imaging (fMRI) during completion of several reward processing paradigms. Two of these involve both a normal "safe" context and a threat context manipulation (threat of mild electrodermal shock that is periodically cycled throughout the task). Another paradigm involves making decisions to either approach reward or forego a reward when this decision conflicts with the likelihood of an aversive outcome. This is known as approach-avoidance conflict (AAC). This battery will provide a comprehensive characterization of reward processing behavior and circuit function and establish its relationship to treatment processes, as well as how such processes may vary as a function of threat.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomization will be stratified based upon baseline presence/absence of MDD and will occur using pre-specified block randomization with randomly-sized blocks of either 4 or 6 to ensure near-equal distribution of participants with and without comorbid MDD between the two arms over time, while avoiding the ability for study personnel to predict treatment assignment of the next participant. Blocks will involve various orderings of participant assignment, each block will be assigned a number, and a random list generator will then order the block sequences prior to the start of the study. This will ensure equal numbers of participants with and without MDD are assigned to each treatment condition and limit predictability of assignment.
| Arm | Type | Receives |
|---|---|---|
| Immediate Treatment | Experimental | Behavioral: Cognitive Processing TherapyThose individuals randomized to immediate treatment will commence individual cognitive processing therapy (CPT) with an assigned study therapist, following the completion of baseline procedures. |
| Delayed Treatment | Placebo comparator | Behavioral: Cognitive Processing TherapyIndividuals randomized to the delayed treatment condition will be informed after randomization that their treatment will start in 6-8 weeks (the approximate period it will take for individuals in the immediate treatment arm to complete CPT and post-treatment assessments). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- English as primary language, and comprehension suitable to understand experimenter instructions.
- Current and chronic syndromic PTSD, defined as being exposed to a DSM-5 Criterion A traumatic event, with the presence DSM-5 qualifying PTSD symptoms for at least 3 months, as assessed by the Clinician-Administered PTSD Scale for DSM-5.
- Able and willing to undergo functional magnetic resonance imaging (fMRI).
- Willingness to participate in repeated assessments and as part of a delayed treatment group.
Key exclusion criteria (11 listed)
- Evidence of current or prior history of psychosis or bipolar disorder as evidenced by self-report or clinical interview.
- Active substance dependence within the past 6 months as evidenced by clinical interview.
- Current regular psychiatric medication use (i.e. antidepressants), except for as-needed benzodiazepine or opiate medication no more than three times per week, on average, or for short-duration stimulant medication for attention deficit hyperactivity disorder that can be skipped within 24 hours of study visits.
- A recent (<6 months) suicide attempt or current active ideation with intent.
- Unremovable ferrous metal in body.
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 |
|---|---|---|
| Cognitive Processing TherapyAlso: CPTCognitive processing therapy is a widely-utilized, empirically-supported treatment developed for PTSD. It is based on a cognitive theory of trauma which emphasizes the impact of trauma on belief systems and the development of "stuck points", which are unhealthy, unrealistic, and maladaptive ways of thinking that serve to maintain unhealthy beliefs and reinforce PTSD symptoms. | Behavioural | Delayed Treatment, Immediate Treatment |
Primary outcome
Within subject beta coefficients for each parametrically modulated regressor of the Reinforcement Learning Task with Threat
Time frame: [10 weeks]
The changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation associated with individual trial-by-trial reinforcement learning computational model parameters at the time of choice valuation (expected reward value during safe contexts and expected reward value during threat contexts) and choice outcome (reward prediction errors during safe contexts and reward prediction errors during threat contexts).
3 secondary outcomes
Within-subject BOLD contrast for unexpected absence of juice vs. expected absence of juice (negative temporal Prediction Errors) for safe and threat contexts.
Time frame: [10 weeks]
Within-subject BOLD contrast for the unexpected delivery of juice vs. the expected delivery of juice (positive temporal Prediction Errors) for safe and threat contexts.
Time frame: [10 weeks]
Within subject beta coefficients for each parametrically modulated regressor of an approach avoidance conflict task.
Time frame: [10 weeks]
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 1 May 2026.
- Individual participant dataSharing planned: No
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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.
Gregory A Fonzo, PhD principal investigator
The University of Texas at Austin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Processing Therapy in people with Post Traumatic Stress Disorder and Diminished Pleasure, run by University of Texas at Austin 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 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 1 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. Some participants in this study may receive a placebo. 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 Lauren Enten, B.S.A (512-495-5856, fonzolab@austin.utexas.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Within subject beta coefficients for each parametrically modulated regressor of the Reinforcement Learning Task with Threat (time frame: [10 weeks]). 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 1 May 2026.