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NCT Number: NCT06096740

Psychotherapy Effects on Reward Processing in PTSD

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.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Health Discovery Building (HDB), 1601 Trinity St., Bldg B., Z0600

Austin, Texas, 78712, United States

Location status: Recruiting

Location contact

Greg Fonzo, Ph.D.

PRINCIPAL_INVESTIGATOR

Lauren Enten, B.S.A.

CONTACT

[email protected]

512-495-5856

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.
  • 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.

Treatment and study plan

cognitive processing therapy

Behavioral

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.

Other names: CPT

Primary outcomes

  1. 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).

Secondary outcomes

  1. 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]

    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.

  2. 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]

    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.

  3. Within subject beta coefficients for each parametrically modulated regressor of an approach avoidance conflict task.

    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, expected threat value, and conflict between reward and threat value), anticipation (expected reward and threat value), and choice outcome (reward and threat prediction errors).

Other outcomes

  1. Change in total score of the Clinician Administered PTSD Scale for DSM-5 from baseline to 10 weeks

    Time frame: 10 weeks

    A structured clinical interview measure of PTSD symptom severity

  2. Change in total score of the PTSD Checklist for DSM-5 from baseline to 10 weeks

    Time frame: 10 weeks

    A self-report measure of PTSD symptom severity

Study contacts

Contact information is provided by the study sponsor or research team.

Lauren Enten, B.S.A

CONTACT

[email protected]

512-495-5856

Sponsors and collaborators

Lead sponsor

University of Texas at Austin

Other

Registry information

Official study title

The Effects of Trauma-focused Psychotherapy on Reward Circuitry Function and Information Encoding

Acronym: PERPP

Important dates

Study start
2024
Primary completion
2029
Study completion
2029
First posted
Oct 24, 2023
Registry last updated
May 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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