Clinical trial NCT02736929: The Effect of Reducing Posttraumatic Stress Disorder Symptoms on Cardiovascular Risk
Official title: The Effect of Reducing Posttraumatic Stress Disorder Symptoms on Cardiovascular Risk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: PTSD
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2016-04-13
Enrollment: 112
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Some individuals who are exposed to traumatic events experience both psychological and cardiovascular changes that affect their health and well-being. The purpose of this study is to learn more about how reducing the psychological symptoms (such as those that occur with posttraumatic stress disorder, or PTSD) affects cardiovascular systems that regulate heart and blood pressure.

Detailed description: There is a fundamental gap in the understanding of how a diagnosis of post-traumatic stress disorder (PTSD) portends excess risk of coronary heart disease (CHD). This is primarily because of two reasons: (1) the core studies which provide support for an association between PTSD and CHD risk depended on lengthy follow-up periods with no repeat measurement of either PTSD or other related cardiovascular risk factors; (2) PTSD is highly comorbid with both adverse health behaviors and with psychiatric comorbidity that also vary across time and could largely explain the association between PTSD and increased risk of CHD. The long-term goal is to better understand whether there is a direct link between PTSD and CHD risk, as well as to ascertain the role of candidate pathophysiological mechanisms. The study proposed in this application is designed to examine how changes in PTSD symptoms following an established therapeutic intervention (Cognitive Processing Therapy) affect CHD disease pathways in individuals with PTSD. This design will permit an evaluation of the hypothesis that individuals who show significant improvement in PTSD symptoms will also show improvement in CHD risk biomarkers, and individuals who fail to show improvement or show worsening PTSD symptoms, will show no change or worsening in CHD biomarker activity. The study will also provide an evaluation of the role of key stress-related CHD biomarkers as mechanisms underlying the increased CHD risk burden associated with PTSD. Choice of CHD biomarkers focused on the established association of PTSD with chronic activation of stress response systems and includes autonomic nervous system dysregulation, chronic systemic inflammation, and vascular endothelial dysfunction. The proposed research is significant because it is expected to provide knowledge of the role of both the direct impact of PTSD symptoms on CHD risk pathways and the role of these systems as candidate mechanisms underlying the relationship between PTSD and CHD risk. By better defining how PTSD is a risk factor for CHD, as well as identifying the disease pathways involved, the proposed study will help inform strategies for CHD prevention, as well as guide optimal medical management for vulnerable men and women with PTSD, especially in those who refrain or who are refractory to psychiatric treatment.

Eligibility criteria: Inclusion Criteria:

* Is between the ages of 40 and 65;
* Has current PTSD lasting at least three months, based on the Clinician Administered PTSD Scale (CAPS), DSM 5 version, with a CAPS total score of 25 or greater; and
* Will have been stable on any current psychiatric medications for four weeks prior to the Time 1 assessment.

Exclusion Criteria:

* Is currently participating in evidence-based trauma focused therapy (e.g., CPT, prolonged exposure) for PTSD (current or past 6 months);
* Has current dementia or other memory loss condition, as indicated by self-report or as indicated by scores less than 20 on the Montreal Cognitive Assessment (MoCA);
* Has current psychotic spectrum disorder or bipolar disorder;
* Has current uncontrolled substance use disorder that would interfere with his/her ability to perform study procedures;
* Has a urine drug screen positive for cocaine and/or methamphetamine and reports regular use of that substance;
* Has severely impaired hearing or speech;
* Is pregnant;
* Has established heart disease, abnormal heart rhythm, advanced cancer, or epilepsy
* Has HIV positive status with unstable disease status and/or unstable medication use;
* Has current exposure to ongoing trauma (e.g., physically abusive relationship);
* Has prominent suicidal or homicidal ideation (as assessed through a clinical interview);
* Has a serious/terminal illness or other health problem that would prohibit participation in the study;
* Has an inflammatory condition such as infection, fever, one-month history of accident or surgery, rheumatoid arthritis, lupus, or inflammatory bowel disease.
* Is unwilling to accept randomization; or
* Cannot agree to attend therapy sessions at least once per week.

Primary outcomes:
measure: Change From Baseline to Post-Intervention in 24-hour Heart Rate Variability (HRV) Estimated From the Standard Deviation of the Interbeat Interval of Normal Sinus Beats (SDNN)
timeFrame: Baseline & post-intervention (up to 20 weeks)
Secondary outcomes:
measure: Change From Baseline to Post-Intervention in 24-hour Heart Rate Variability (HRV) Estimated From Low Frequency HRV (LF-HRV)
timeFrame: Baseline & post-intervention (up to 20 weeks)
measure: Change in Heart Rate Variability (HRV) Measured by Holter Monitor, as Indicated by High Frequency HRV (HF-HRV)
timeFrame: Baseline & post-intervention (up to 20 weeks)
measure: Change in Heart Rate Variability (HRV) as Measured by Root Square Mean of Successive Interbeat Interval Differences (RMSSD)
timeFrame: Baseline & post-intervention (up to 20 weeks)
measure: Change From Baseline to Post-Intervention in 24-hour Urinary Excretion of Norepinephrine
timeFrame: Baseline & post-intervention (up to 20 weeks)
measure: Change From Baseline to Post-Intervention in 24-hour Urinary Excretion of Epinephrine
timeFrame: Baseline & post-intervention (up to 20 weeks)
measure: Change From Baseline to Post-Intervention in High Sensitivity C-Reactive Protein (Hs-CRP)
timeFrame: Baseline & post-intervention (up to 20 weeks)
measure: Change From Baseline to Post-Intervention in Flow-Mediated Dilation (FMD)
timeFrame: Baseline & post-intervention (up to 20 weeks)
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Lana Watkins, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Jean C. Beckham, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: LoSavio ST, Beckham JC, Wells SY, Resick PA, Sherwood A, Coffman CJ, Kirby AC, Beaver TA, Dennis MF, Watkins LL. The effect of reducing posttraumatic stress disorder symptoms on cardiovascular risk: Design and methodology of a randomized clinical trial. Contemp Clin Trials. 2021 Mar;102:106269. doi: 10.1016/j.cct.2021.106269. Epub 2021 Jan 8.