## Protocol Section
### Identification Module
**NCT ID:** NCT06429293

**Brief Title:** Impact of Cognitive Behavioral Therapy on PTSD-CVD Link

**Official Title:** Impact of Cognitive Behavioral Therapy on Neural, Inflammatory, & Autonomic Markers in a Sample With PTSD and Cardiovascular Risk: Protocol for a Pilot Randomized Controlled Trial

#### Organization Study ID Info
**ID:** 2023P001621
#### Organization
**Class:** OTHER
**Full Name:** Massachusetts General Hospital
### Status Module
#### Completion Date
**Date:** 2026-07-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2026-07-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-07-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-08
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** American Heart Association

#### Lead Sponsor

**Class:** OTHER

**Name:** Massachusetts General Hospital

#### Responsible Party

**Investigator Affiliation:** Massachusetts General Hospital

**Investigator Full Name:** Michael T. Osborne

**Investigator Title:** Clinician Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This is a pilot randomized controlled trial to assess the impact of a first-line treatment for posttraumatic stress disorder (PTSD) (Cognitive Processing Therapy; CPT) versus waitlist control on mechanisms of cardiovascular disease (CVD) risk. Further, this study will test the hypothesis that CPT reduces CVD risk through its effects on inflammation and autonomic function and that these changes are driven by changes in stress-related neural activity (SNA)

**Detailed Description:** This study is a randomized controlled trial of CPT compared to waitlist control that is testing the effects of CPT on mechanisms of the PTSD-CVD link. Enrollment began in 2023 and is projected to continue through 2026. Participants include individuals with PTSD and CVD risk recruited from the Boston area (N = 30). Treatment assignment is randomized and stratified by sex. Participants are randomized to CPT (n = 15) or waitlist control (n = 15). Potentially eligible participants complete a screening visit to confirm inclusion/exclusion criteria. Upon confirmation of eligibility, participants are scheduled for a baseline session, where they complete surveys, brain and peripheral imaging, and resting measures of autonomic function. Following the baseline visit, participants are randomized into CPT or the waitlist control group. Those randomized to CPT complete sessions via telehealth. Following a 12-week treatment period, participants attend the post-treatment visit, consisting of the same assessments administered at baseline. Participants randomized to waitlist are offered CPT upon completion of the post-treatment visit.

### Conditions Module

**Conditions:**

- Posttraumatic Stress Disorder

**Keywords:**

- Cardiovascular disease

- Inflammation

- Autonomic function

- Stress-related neural activity

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Participants are randomized to 12 weeks of cognitive processing therapy or waitlist control.

##### Masking Info

**Masking:** SINGLE

**Masking Description:** Individuals who interpret images and data will be blinded to assigned intervention

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 12 week treatment period of cognitive processing therapy followed by a post-treatment visit.

**Intervention Names:**

- Behavioral: Cognitive processing therapy

**Label:** Cognitive processing therapy

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants randomized to waitlist are offered CPT upon completion of the post-treatment visit.

**Label:** Control waitlist

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cognitive processing therapy

**Description:** The active intervention is Cognitive Processing Therapy (CPT) is a gold-standard cognitive behavioral therapy for PTSD. The CPT intervention consists of 12 60-minute sessions teaching skills to challenge trauma-relevant cognitions that are distorted or unhelpful. Trauma-relevant cognitions fall into five themes that are highlighted during treatment: safety, trust, power/control, esteem, and intimacy. The empirical base for CPT is strong with numerous studies demonstrating that it results in significant reduction of PTSD symptoms regardless of trauma type and that it is 89% more effective than control treatment. CPT has been successfully implemented in virtual formats with comparable efficacy levels to that of in-person CPT. CPT sessions for this study will be conducted virtually by a CPT-trained clinician

**Name:** Cognitive processing therapy

**Type:** BEHAVIORAL

### Outcomes Module

#### Primary Outcomes

**Description:** Measured via FDG-PET imaging

**Measure:** Arterial inflammation

**Time Frame:** Baseline and 12-weeks

**Description:** Calculated from the average resting HRV collected at baseline and post-treatment visits

**Measure:** Heart rate variability

**Time Frame:** Baseline and 12-weeks

#### Secondary Outcomes

**Description:** Measured as bone marrow activity via FDG-PET imaging

**Measure:** Leukopoiesis

**Time Frame:** Baseline and 12-weeks

**Description:** Heart rate in beats per minute

**Measure:** Heart rate

**Time Frame:** Baseline and 12-weeks

**Description:** Systolic and diastolic pressure

**Measure:** Blood pressure

**Time Frame:** Baseline and 12-weeks

**Description:** MRI measurements of atherosclerotic plaque components including necrotic tissue, loose connective tissue, and hemorrhage using black-blood imaging techniques

**Measure:** MRI based arterial plaque components (such as necrotic tissue, loose connective tissue, and hemorrhage)

**Time Frame:** Baseline and 12-weeks

**Description:** Measurements of wall thickness as an assessment of atherosclerotic plaque

**Measure:** MRI based arterial wall thickness

**Time Frame:** Baseline and 12-weeks

**Description:** Structural assessment of brain centers to assess volume and density of neural centers involved in the stress response

**Measure:** MRI based brain structure assessments of volume and density

**Time Frame:** Baseline and 12-weeks

**Description:** Connectivity assessment using mapping on functional MRI at baseline and in response to emotional faces of neural centers involved in the stress response to determine the interplay between neural centers before and after therapy by measuring alterations in blood oxygen content under various conditions in different parts of the brain

**Measure:** MRI based brain connectivity (by measuring changes in blood flow across networks of neural centers at rest and with an emotional task)

**Time Frame:** Baseline and 12-weeks

**Description:** Activation assessment using functional MRI at both rest and in response to emotional faces of neural centers involved in the stress response before and after therapy by measuring blood flow under various conditions to different parts of the brain

**Measure:** MRI based brain activation (via measuring blood flow in important neural centers at rest and with an emotional task using functional MRI)

**Time Frame:** Baseline and 12-weeks

**Description:** Measurement of axonal integrity using diffusion tensor imaging on MRI to determine the strength connections between important brain centers and neural networks related to stress perception in PTSD before and after therapy

**Measure:** Axonal integrity of resting neural connections between brain centers using MRI

**Time Frame:** Baseline and 12-weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* age 18-65 years (upper limit chosen to optimize changes in brain activation that diminish with age);
* criterion A trauma exposure and PTSD symptoms (clinically significant symptoms in at least two symptom clusters);
* subclinical atherosclerotic CVD (e.g., coronary, cerebrovascular, or peripheral arterial plaque or calcifications on imaging), clinical atherosclerotic CVD (e.g., myocardial infarction or revascularization), or increased risk for atherosclerotic CVD (i.e., \>2 of hypertension, diabetes mellitus, hyperlipidemia, and active smoking) ability to understand and sign informed consent
* fluent English speaker.

Exclusion Criteria:

* history of stroke, brain surgery, seizure
* use of certain CVD medications (e.g., beta-blockers, high-intensity statins \[e.g., rosuvastatin 20/40 mg and atorvastatin 40/80 mg\], PCSK-9 inhibitors);
* psychiatric or cardiovascular medication change within 4 weeks (i.e., stable regimen is allowed);
* currently in PTSD therapy;
* neurological or systemic inflammatory disease/current anti-inflammatory therapy;
* moderate/severe alcohol/substance use disorder;
* current mania/psychosis;
* weight \>300 lbs., claustrophobia, pregnancy, metal implants that are incompatible with magnetic resonance imaging (MRI), or uncontrolled hyperglycemia (for imaging);
* significant radiation exposure (\>2 nuclear tests, computed tomography images, or fluoroscopic procedures) for research purposes during the preceding 12-months.

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** MOSBORNE@PARTNERS.ORG

**Name:** Michael Osborne, MD

**Phone:** 6177261843

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Boston

**Contacts:**

***Contact 1:***

- **Email:** mosborne@mgh.harvard.edu

- **Name:** Michael Osborne, MD

- **Role:** CONTACT

**Country:** United States

**Facility:** Massachusetts General Hospital

**State:** Massachusetts

**Status:** RECRUITING

**Zip:** 02114

### IPD Sharing Statement Module

**Access Criteria:** To be determined based on website used

**Description:** Deidentified data from primary endpoints and analyses will be made available on a public website following study completion.

**IPD Sharing:** YES

**Time Frame:** Within 6 months of study completion

### References Module

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#### See Also Links

**Label:** About Multiple Cause of Death

**URL:** https://wonder.cdc.gov/mcd-icd10.html

**Label:** The Life Events Checklist for DSM-5 (LEC-5)

**URL:** https://www.ptsd.va.gov/professional/assessment/te-measures/life_events_checklist.asp

**Label:** The PTSD checklist for DSM-5 (PCL-5)

**URL:** https://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000040921

- Term: Stress Disorders, Traumatic

- ID: D000068099

- Term: Trauma and Stressor Related Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: BC26

- Name: Wounds and Injuries

### Condition Browse Module - Browse Leaves

- ID: M10293

- Name: Inflammation

- Relevance: LOW

- As Found: Unknown

- ID: M24916

- Name: Stress Disorders, Traumatic

- Relevance: LOW

- As Found: Unknown

- ID: M16103

- Name: Stress Disorders, Post-Traumatic

- Relevance: HIGH

- As Found: Posttraumatic Stress Disorder

- ID: M17685

- Name: Wounds and Injuries

- Relevance: LOW

- As Found: Unknown

- ID: M222

- Name: Trauma and Stressor Related Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000013313

- Term: Stress Disorders, Post-Traumatic

### Misc Info Module

- Version Holder: 2024-05-31
