Clinical trial NCT06096740: Psychotherapy Effects on Reward Processing in PTSD
Official title: The Effects of Trauma-focused Psychotherapy on Reward Circuitry Function and Information Encoding
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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
Lead sponsor: University of Texas at Austin
Sponsor class: OTHER
First posted: 2023-10-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief 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. 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:

1. Quantify, under conditions of safety (no threat), how PTSD psychotherapy alters reward circuit function and information encoding.
2. Identify how presence of threat augments PTSD psychotherapy effects on reward circuit function and information encoding.
3. (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.

Eligibility criteria: 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.

Primary outcomes:
measure: Within subject beta coefficients for each parametrically modulated regressor of the Reinforcement Learning Task with Threat
timeFrame: [10 weeks]
Secondary outcomes:
measure: Within-subject BOLD contrast for unexpected absence of juice vs. expected absence of juice (negative temporal Prediction Errors) for safe and threat contexts.
timeFrame: [10 weeks]
measure: 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.
timeFrame: [10 weeks]
measure: Within subject beta coefficients for each parametrically modulated regressor of an approach avoidance conflict task.
timeFrame: [10 weeks]
Other outcomes:
measure: Change in total score of the Clinician Administered PTSD Scale for DSM-5 from baseline to 10 weeks
timeFrame: 10 weeks
measure: Change in total score of the PTSD Checklist for DSM-5 from baseline to 10 weeks
timeFrame: 10 weeks
Locations:
city: Austin
country: United States
facility: Health Discovery Building (HDB), 1601 Trinity St., Bldg B., Z0600
state: Texas
Study officials:
affiliation: The University of Texas at Austin
name: Gregory A Fonzo, PhD
role: PRINCIPAL_INVESTIGATOR
References: