Clinical trial NCT04498754: An Evaluation of Insomnia Treatment to Reduce Cardiovascular Risk in Patients With Posttraumatic Stress Disorder
Official title: An Evaluation of Insomnia Treatment to Reduce Cardiovascular Risk in Patients With Posttraumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Insomnia
Posttraumatic Stress Disorder
Cardiovascular Risk Factor
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2020-08-04
Enrollment: 150
Sex: ALL
Minimum age (years): 40
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants who are originally assigned to the minimal contact control condition will be invited to receive the active condition treatment after their study involvement has been completed, but no additional data will be collected from them.
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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 \<8 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), and that sleep disorder is the primary cause of their sleep complaint (participants with restless legs syndrome who also have insomnia disorder can be included in the study);
* 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
* Has uncontrolled hypertension (screening office BP \> 160/100 mm Hg)

Primary outcomes:
measure: Change in nighttime blood pressure
timeFrame: Baseline and post-treatment (approximately eight weeks)
measure: Change in nighttime blood pressure
timeFrame: Baseline and 6-month follow-up
measure: Change in nighttime blood pressure dipping
timeFrame: Baseline and post-treatment (approximately eight weeks)
measure: Change in nighttime blood pressure dipping
timeFrame: Baseline and 6-month follow-up
measure: Change in vascular endothelial function
timeFrame: Baseline and post-treatment (approximately eight weeks)
measure: Change in vascular endothelial function
timeFrame: Baseline and 6-month follow-up
measure: Change in nighttime sympathetic nervous system activity
timeFrame: Baseline and post-treatment (approximately eight weeks)
measure: Change in nighttime sympathetic nervous system activity
timeFrame: Baseline and 6-month follow-up
measure: Change in 10-year atherosclerotic cardiovascular disease risk
timeFrame: Baseline and post-treatment (approximately eight weeks)
measure: Change in 10-year atherosclerotic cardiovascular disease risk
timeFrame: Baseline and 6-month follow-up
measure: Change in insomnia severity
timeFrame: Baseline and post-treatment (approximately eight weeks)
measure: Change in insomnia severity
timeFrame: Baseline and 6-month follow-up
measure: Change in sleep efficiency
timeFrame: Baseline and post-treatment (approximately eight weeks)
measure: Change in sleep efficiency
timeFrame: Baseline and 6-month follow-up
Secondary outcomes:
measure: Change in subjective sleep quality
timeFrame: Baseline and 6-month follow-up
measure: Change in subjective sleep quality
timeFrame: Baseline and post-treatment (approximately eight weeks)
measure: Change in quality of life
timeFrame: Baseline and 6-month follow-up
measure: Change in quality of life
timeFrame: Baseline and post-treatment (approximately eight weeks)
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke Health
name: Jean C Beckham, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke Health
name: Andrew Sherwood, PhD
role: PRINCIPAL_INVESTIGATOR
References: