Clinical trial NCT05365607: NightWare and Cardiovascular Health in Adults With PTSD
Official title: NightWare Therapeutic Platform for Improving Cardiovascular Health in Adults With Nightmares Associated With PTSD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Posttraumatic Stress Disorder
Cardiovascular Diseases
Autonomic Dysfunction
Vascular Stiffness
Nightmare
Endothelial Dysfunction
Keywords: sleep
oxidative stress
aging
inflammation
sex/gender
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2022-05-09
Enrollment: 40
Sex: ALL
Minimum age (years): 22
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo (i.e., sham intervention) controlled parallel pilot study
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether NightWare therapeutic intervention improves biomarkers of vascular aging and autonomic function in adults with nightmares related to PTSD.

Detailed description: Posttraumatic stress disorder (PTSD) is linked to accelerated aging and is associated with increased risk of early-onset cardiovascular disease (CVD) in both men and women. The pathophysiological link between PTSD and CVD is complex and multi-factorial that likely involves premature vascular aging (i.e., large elastic arterial stiffening and vascular endothelial dysfunction) and autonomic dysfunction (e.g., reduced cardiovagal baroreflex sensitivity \[cBRS\] and heart rate variability \[HRV\]), along with other mechanisms. Vascular aging and autonomic dysfunction are key antecedents in the development of CVD and individuals with PTSD have greater arterial stiffening, endothelial dysfunction and reductions in cBRS and HRV compared to those without PTSD. The mechanisms by which PTSD contributes to greater vascular and autonomic dysfunction are not completely understood. Sleep is important for cellular and tissue repair, free radical detoxification and reducing oxidative stress and inflammation. Sleep disturbance is a hallmark symptom of PTSD and is associated with biomarkers of vascular aging, autonomic dysfunction and increased risk of CVD. Nightmares, a central feature of PTSD associated-sleep disturbance, are a debilitating symptom that can lead to insomnia or sleep deprivation, daytime sleepiness or fatigue, mood disturbances, cognitive impairments, behavioral problems, or other sequela, that ultimately causes clinically significant distress and impairment in social, occupational and physiological function, as well as increased CVD risk. As such, therapeutic strategies and interventions aimed at reducing nightmare-associated sleep disturbances in individuals with PTSD are clinically important for improving sleep quality, cardiovascular health and risk for future age-associated CVD.

Various psychotherapeutic (e.g., imagery rehearsal therapy \[IRT\]) and pharmacological (e.g., prazosin) interventions are available for treatment of nightmares associated with PTSD. However, the evidence for their efficacy for addressing sleep disturbances is inconsistent, particularly with pharmaceuticals, and implementation barriers and poor adherence exist with psychotherapy. As such, novel alternative approaches, including the use of digital medicine such as app-based and digital platforms are being developed to improve treatment delivery. NightWare™ digital therapeutic system is one such novel platform that was recently granted Breakthrough Device designation by the FDA for the treatment of nightmares in adults with PTSD. NightWare uses a proprietary application on the Apple Watch® to collect biometric data (i.e., heart rate \[HR\] and body movement) to learn sleep patterns to create a stress Index. When an individual exceeds this index due to entering a nightmare, NightWare intervenes by sending vibrotactile feedback to the Apple Watch, arousing the individual and interrupting the nightmare without waking or disrupting sleep. Through machine learning, NightWare continually refines its model and knowledge of the person's response, consequently leading to fewer nightmare associated awakenings. In unpublished preliminary studies, NightWare was shown to be safe (no change in suicide risk or daytime sleepiness) and a tendency to have greater improvement in objective measures of sleep quality (i.e., Pittsburgh Sleep Quality Index \[PSQI\] and amendment for PTSD \[PSQI-A\]) compared to sham (NightWare but intervention disabled, i.e., no vibration). Whether NightWare improves cardiovascular health in adults with PTSD-related nightmares has yet to be studied.

Accordingly, the investigators are proposing a randomized, double-blind, placebo (i.e., sham intervention) controlled parallel pilot study that will provide the first clinical evidence for the efficacy of the NightWare digital therapeutic system to improve cardiovascular health outcomes in adults with PTSD-related nightmares.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of PTSD via American Psychiatric Association PTSD diagnostic criteria in the fifth edition of its Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
2. Self-report having repetitive nightmares contributing to disrupted sleep
3. age \>22 years (rationale is because the device has only been used in adults in 22 years and older);
4. resting blood pressure (BP, \<160/100 mmHg);
5. fasted glucose \<126 mg/d;
6. non-smokers;
7. no use of vitamin supplements or anti-inflammatory medications, or willing to stop 1 month prior to the vascular visit;
8. Pittsburgh Sleep Quality Index (PSQI) score 6 or higher;
9. Epworth Sleepiness Scale (ESS): Question #8 score above "0" will prompt an additional question: Does individual drive ("get behind the wheel") when they are drowsy? The answer must be "No" to be enrolled in the study due to safety concerns;
10. Wireless Internet and two power outlets where they sleep;
11. Willingness not to use any other application which collects heart rate data on the phone and watch that is used for NightWare.

Exclusion Criteria:

1. uncontrolled hypertension;
2. current or preexisting CVD or cancers (with the exception of past skin cancers) or active infection;
3. diabetes;
4. thyroid dysfunction, defined as an ultrasensitive TSH \<0.5 or \>5.0 mU/L; volunteers with abnormal TSH values will be re-considered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement; or other problems that would interfere with participation in the study;
5. pregnancy or currently breast feeding;
6. current use (or within previous 6 months) of hormone therapy in postmenopausal women;
7. current substance (including marijuana) or alcohol use disorder (past 12 months) per the SCID-5 (see methods of Research Strategy). Adults with past substance or alcohol use disorders will be allowed to participate.
8. Prazosin use; however, participant may be included if tapered by prescribing provider. Taper must be completed and individual must be off prazosin for 2 days prior to enrollment;
9. Participants will be excluded if they report elevated acute risk for suicidal self-directed violence warranting immediate intervention (e.g., suicidal ideation with intent, evaluated by the Columbia-Suicide Severity Rating Scale \[C-SSRS\]).
10. Current use of varenicline, beta-blockers (unless ophthalmic solutions), or non-dihydropyridines;
11. Shift workers (due to circadian rhythm disruption);
12. Moderate or Severe obstructive sleep apnea (either diagnosed or determined during screening with the WatchPat \[AHI≥15\];
13. Diagnosis of narcolepsy;
14. Known sleepwalking;

16) Acting out of dreams prior to PTSD trauma; 17) Diagnosis or suspicion of dementia

Primary outcomes:
measure: Change in large elastic artery stiffness -carotid artery
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in endothelial function
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in 1utonomic function - BRS
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
Secondary outcomes:
measure: Change in large elastic artery stiffness
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in autonomic function - HRV
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
Other outcomes:
measure: Change in PSQI
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in PSQI-A
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in Epworth sleepiness scale (ESS)
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in CESD
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in SF-36
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in PCL-5
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in Nightmare disorder index
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in CSSR-S
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in Norepinephrine
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in Oxidized LDL
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in Total antioxidant status
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in Interleukin-6
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
measure: Change in C-Reactive Protein
timeFrame: Measured before and after 6 weeks of NightWare and sham conditions
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Denver
country: United States
facility: University of Colorado CCTSI CTRC
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Kerrie Moreau, PhD
role: PRINCIPAL_INVESTIGATOR
References: