An Evaluation of Insomnia Treatment to Reduce Cardiovascular Risk in Patients With Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a chronic, debilitating psychiatric disorder that is associated with an increased risk of death due to cardiovascular disease (CVD). Most individuals with PTSD also have Insomnia Disorder. Sleep quality is also associated with risk factors for CVD. The objective of this study is to examine how insomnia contributes to CVD risk among people with PTSD. The investigators will also examine whether this risk can be decreased with treatment for Insomnia Disorder.

Study Overview

• Status: Recruiting
• Conditions: Insomnia; Posttraumatic Stress Disorder; Cardiovascular Risk Factor
• Intervention / Treatment: Behavioral: Cognitive Behavior Therapy for Insomnia; Behavioral: Weekly phone contacts

Detailed Description

Posttraumatic stress disorder (PTSD) is a disabling and costly psychiatric disorder that is estimated to occur in 20% of individuals who are exposed to a traumatic event and is chronic in one third of cases. In addition to its negative impact on quality of life, there is substantial evidence that PTSD (even after controlling for depression and other risk factors) is associated with a markedly increased risk of cardiovascular morbidity and mortality. However, the mechanisms for the association between PTSD and cardiovascular disease (CVD) risk are not well understood. Although adverse health behaviors, including cigarette smoking, alcohol abuse and poor medication adherence are common in PTSD, recent prospective studies show that they do not account for the magnitude of CVD risk among individuals with PTSD. The investigators propose to test our central hypothesis by evaluating whether CBT-I results in improved biomarkers of CVD risk among those with PTSD. Well established biomarkers of CVD related morbidity and mortality will be used including measures of vascular endothelial function measured by brachial artery flow-mediated dilation (FMD), nighttime blood pressure (BP) dipping measured using 24-hour ambulatory blood pressure monitoring (ABPM), and sympathetic nervous system (SNS) activity as measured by 24-hour urinary catecholamines. Investigators will also assess lipid profile, which along with BP is a modifiable component with marked impact on the atherosclerotic cardiovascular disease (ASCVD) risk score. The primary sleep parameter of interest is objectively-measured sleep efficiency (through actigraphy), although self-report insomnia measures and sleep related arousal will also be measured. The rationale for the proposed research is that once it is established that insomnia is an important and modifiable symptom conveying increased CVD risk in this population, the development of new and innovative approaches to integrating insomnia treatment with PTSD-focused interventions can be developed. 150 men and women with comorbid PTSD and insomnia disorder will be randomly assigned with a 2:1 ratio to 8-week cognitive behavioral therapy-Insomnia (CBT-I) intervention or a waiting period control condition. Sleep quality parameters and CVD risk biomarkers will be assessed at pre-randomization baseline, post-intervention, and at a 6-month follow-up. The study is designed to evaluate the association between insomnia and CVD risk biomarkers among persons with PTSD, and determine whether improvements in insomnia symptoms are associated with improvements in CVD risk biomarkers.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tiffany Mosher, MA; Phone Number: (919) 684-1079; Email: tiffany.mosher@duke.edu
• Study Contact Backup: Name: Angela Kirby, MS; Phone Number: 175526 919-286-0411; Email: angela.kirby@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27706
      • Recruiting
      • Duke University Medical Center
      • Contact: Angela C. Kirby, M.S.; Phone Number: 5526 919-286-0411; Email: angela.kirby@va.gov
      • Principal Investigator: Jean C Beckham, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 59 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is between 40-59 years old;
• Has a current diagnosis of chronic PTSD (at least 3 months duration) based on the Clinician Administered PTSD Scale DSM-5 version (Weathers et al., 2013);
• Has a current diagnosis of ID as defined in the International Classification of Sleep Disorders (ICSD-3; American Academy of Sleep Medicine, 2014)

Exclusion Criteria:

• Has a history of CVD events, including myocardial infarction, stroke, transient ischemic attack, or coronary revascularization;
• Has diagnosis of congestive heart failure or coronary artery disease based on results of diagnostic testing;
• Has a current alcohol use or substance use disorder (those who meet lifetime but not current alcohol or substance use disorder will be included);
• Is currently participating in or has recently (past 6 months) participated in an evidence-based trauma focused therapy for PTSD;
• Has cognitive impairment as evidenced by less than 20 on the Montreal Cognitive Assessment scale (M0CA; Nasreddine et al., 2005);
• Meets criteria for a psychotic spectrum disorder or bipolar disorder;
• Has severely impaired hearing or speech;
• Is pregnant;
• Does not use benzodiazepines for sleep, and if prescribed benzodiazepines for some other use (e.g., anxiety, panic attacks), uses them fewer than four times in a one month period.;
• Is not stable (medications and dose stable for one month) on any other current psychoactive and/or cardiovascular medications or will not be stable on these medications during the course of the study;
• Works night shift;
• Is participating in another interventional study to address insomnia;
• 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 nonclinically significant or sub-threshold insomnia as indicated by a score of <14 on the Insomnia Severity Index;
• Has seizures (based on clinical interview and self-report);
• Has a body mass index of 45 or greater;
• Has sleep apnea (based on the overnight assessment described below) or a positive sleep apnea screen;
• Has restless leg syndrome (based on the Duke Structured Interview for Sleep Disorders (DSISD); Edinger, Wyatt, & Olsen, 2009);
• Has an organic cause of sleep disruption that cannot be addressed by cognitive-behavioral changes (e.g., hyperthyroidism), as determined by the DSISD;
• Has excessive daytime sleepiness, defined as a score >15 on the Epworth Sleepiness Scale (ESS) or as determined by the DSISD;
• Does not complete sleep diary assessments within 6 hours of rising on at least 5 of the 7 days of the initial assessment period; or
• Cancels or no-shows for two or more Time 1 assessment appointments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive Behavior Therapy for Insomnia (CBT-I); Participants assigned to this arm will receive eight sessions of a well-established, evidence-based therapy called cognitive behavior therapy for insomnia (CBT-I).	Behavioral: Cognitive Behavior Therapy for Insomnia; 8 sessions of treatment for insomnia.; Other Names: CBT-I
Other: Minimal Contact Control Condition; Participants assigned to this condition will be contacted every week for eight weeks and monitored regarding their insomnia symptoms.	Behavioral: Weekly phone contacts; Weekly calls to monitor insomnia symptoms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in nighttime blood pressure	Nighttime systolic and diastolic blood pressure measured by 24-hour ambulatory blood pressure monitor.	Baseline and post-treatment (approximately eight weeks)
Change in nighttime blood pressure	Nighttime systolic and diastolic blood pressure measured by 24-hour ambulatory blood pressure monitor.	Baseline and 6-month follow-up
Change in nighttime blood pressure dipping	Systolic and diastolic blood pressure dipping measured by 24-hour ambulatory blood pressure monitoring, and defined as the percent change in blood pressure from the wake period to the nighttime sleep period.	Baseline and post-treatment (approximately eight weeks)
Change in nighttime blood pressure dipping	Systolic and diastolic blood pressure dipping measured by 24-hour ambulatory blood pressure monitoring, and defined as the percent change in blood pressure from the wake period to the nighttime sleep period.	Baseline and 6-month follow-up
Change in vascular endothelial function	Vascular endothelial function will be measured by vascular ultrasound to determine flow mediated dilation (FMD) of the brachial artery. V	Baseline and post-treatment (approximately eight weeks)
Change in vascular endothelial function	Vascular endothelial function will be measured by vascular ultrasound to determine flow mediated dilation (FMD) of the brachial artery.	Baseline and 6-month follow-up
Change in nighttime sympathetic nervous system activity	Measured by 24 hour urine collection (awake and sleep period collection separated) assayed for catecholamines (epinephrine, norepinephrine) and creatinine.	Baseline and post-treatment (approximately eight weeks)
Change in nighttime sympathetic nervous system activity	Measured by 24 hour urine collection (awake and sleep period collection separated) assayed for catecholamines (epinephrine, norepinephrine) and creatinine.	Baseline and 6-month follow-up
Change in 10-year atherosclerotic cardiovascular disease risk	The risk of having a primary atherosclerotic cardiovascular disease event within 10 years will be based upon the pooled cohort equations model developed by the American College of Cardiology/American Heart Association.	Baseline and post-treatment (approximately eight weeks)
Change in 10-year atherosclerotic cardiovascular disease risk	The risk of having a primary atherosclerotic cardiovascular disease event within 10 years will be based upon the pooled cohort equations model developed by the American College of Cardiology/American Heart Association.	Baseline and 6-month follow-up
Change in insomnia severity	Insomnia measured by the Insomnia Severity Index. The measure has a score range from 0 to 28, with higher scores indicating more severe insomnia.	Baseline and post-treatment (approximately eight weeks)
Change in insomnia severity	Insomnia measured by the Insomnia Severity Index. The measure has a score range from 0 to 28, with higher scores indicating more severe insomnia.	Baseline and 6-month follow-up
Change in sleep efficiency	Sleep efficiency (percent-time asleep during the sleep period) measured by sleep diary and wrist actigraphy.	Baseline and post-treatment (approximately eight weeks)
Change in sleep efficiency	Sleep efficiency (percent-time asleep during the sleep period) measured by sleep diary and wrist actigraphy.	Baseline and 6-month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in subjective sleep quality	Sleep quality will be measured by the Pittsburgh Sleep Quality Index. The scale has a score range of 0 to 21, with lower scores on this measure indicating better sleep quality.	Baseline and 6-month follow-up
Change in subjective sleep quality	Sleep quality will be measured by the Pittsburgh Sleep Quality Index.scale has a score range of 0 to 21, with lower scores on this measure indicating better sleep quality.	Baseline and post-treatment (approximately eight weeks)
Change in quality of life	Quality of life will be measured using the Short Form-36 Health Survey. Scores on this measure range from 0 to 100, with higher scores indicating better quality of life.	Baseline and 6-month follow-up
Change in quality of life	Quality of life will be measured using the Short Form-36 Health Survey. Scores on this measure range from 0 to 100, with higher scores indicating better quality of life.	Baseline and post-treatment (approximately eight weeks)

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Jean C Beckham, PhD, Duke Health; Principal Investigator: Andrew Sherwood, PhD, Duke Health

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Trauma and Stressor Related Disorders; Sleep Initiation and Maintenance Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: PRO00100446

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individual participant data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No