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

Overview

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.

Interventions

• Behavioral Cognitive processing therapy
  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 sign

Primary outcome measures

• Arterial inflammation [Time frame: Baseline and 12-weeks]
• Heart rate variability [Time frame: Baseline and 12-weeks]

Secondary outcome measures (9)

• Leukopoiesis [Time frame: Baseline and 12-weeks]
• Heart rate [Time frame: Baseline and 12-weeks]
• Blood pressure [Time frame: Baseline and 12-weeks]
• MRI based arterial plaque components (such as necrotic tissue, loose connective tissue, and hemorrhage) [Time frame: Baseline and 12-weeks]
• MRI based arterial wall thickness [Time frame: Baseline and 12-weeks]
• MRI based brain structure assessments of volume and density [Time frame: Baseline and 12-weeks]
• 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]
• 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]
• Axonal integrity of resting neural connections between brain centers using MRI [Time frame: Baseline and 12-weeks]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Massachusetts General Hospital — Boston

Publications

• Edmondson D, Cohen BE. Posttraumatic stress disorder and cardiovascular disease. Prog Cardiovasc Dis. 2013 May-Jun;55(6):548-56. doi: 10.1016/j.pcad.2013.03.004. Epub 2013 Apr 6. PMID 23621964
• Edmondson D, von Kanel R. Post-traumatic stress disorder and cardiovascular disease. Lancet Psychiatry. 2017 Apr;4(4):320-329. doi: 10.1016/S2215-0366(16)30377-7. Epub 2017 Jan 19. PMID 28109646
• Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995 Dec;52(12):1048-60. doi: 10.1001/archpsyc.1995.03950240066012. PMID 7492257
• Goldstein RB, Smith SM, Chou SP, Saha TD, Jung J, Zhang H, Pickering RP, Ruan WJ, Huang B, Grant BF. The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Soc Psychiatry Psychiatr Epidemiol. 2016 Aug;51(8):1137-48. doi: 10.1007/s00127-016-1208-5. Epub 2016 Apr 22. PMID 27106853
• Ehlers A, Suendermann O, Boellinghaus I, Vossbeck-Elsebusch A, Gamer M, Briddon E, Martin MW, Glucksman E. Heart rate responses to standardized trauma-related pictures in acute posttraumatic stress disorder. Int J Psychophysiol. 2010 Oct;78(1):27-34. doi: 10.1016/j.ijpsycho.2010.04.009. Epub 2010 May 5. PMID 20450940
• Jovanovic T, Norrholm SD, Sakoman AJ, Esterajher S, Kozaric-Kovacic D. Altered resting psychophysiology and startle response in Croatian combat veterans with PTSD. Int J Psychophysiol. 2009 Mar;71(3):264-8. doi: 10.1016/j.ijpsycho.2008.10.007. Epub 2008 Nov 5. PMID 19013485
• Buckley TC, Kaloupek DG. A meta-analytic examination of basal cardiovascular activity in posttraumatic stress disorder. Psychosom Med. 2001 Jul-Aug;63(4):585-94. doi: 10.1097/00006842-200107000-00011. PMID 11485112
• Pan X, Kaminga AC, Wen SW, Liu A. Catecholamines in Post-traumatic Stress Disorder: A Systematic Review and Meta-Analysis. Front Mol Neurosci. 2018 Dec 4;11:450. doi: 10.3389/fnmol.2018.00450. eCollection 2018. PMID 30564100

Identifiers

NCT: NCT06429293 · 2023P001621

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗