## Protocol Section
### Identification Module
**NCT ID:** NCT06419959

**Brief Title:** NightWare and Cardiovascular Health in Veterans With PTSD

**Official Title:** Improving Cardiovascular Health in Veterans With PTSD by Treating Trauma-Related Nightmares With NightWare

#### Organization Study ID Info
**ID:** CARB-005-23F
#### Organization
**Class:** FED
**Full Name:** VA Office of Research and Development
#### Secondary ID Infos
**Domain:** Veterans Affairs
**ID:** CX002762-01A1
**Type:** OTHER_GRANT
**Domain:** COMIRB
**ID:** 24-0284
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2026-09-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-09-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-10-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-03
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** FED

**Name:** VA Office of Research and Development

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Is US Export:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The purpose of this study is to learn more about the effectiveness of a prescription wrist-wearable device called NightWare (NW) on improving sleep in Veterans with nightmares related to posttraumatic stress disorder (PTSD). The investigators also want to learn whether it improves cardiovascular health among this population.

**Detailed Description:** Posttraumatic stress disorder (PTSD) is associated with profound health consequences in Veterans, including cardiovascular disease (CVD), the leading cause of death in adults in the United States. Trauma-related nightmares, a hallmark of PTSD, are a debilitating symptom that can lead to poor sleep quality and other health issues that ultimately cause clinically significant impairments in daily functioning. Recently, nightmares were reported to be an independent predictor of CVD in Veterans, for reasons that are unclear. Poor sleep is associated with increased CVD risk, possibly by impairing vascular health and nervous system function. Nightmare-related sleep disturbances are often resistant to first-line treatment (e.g., psychotherapy, medications) and even with improvements, residual nightmares and sleep disturbances often persist that still meet clinical significance. Moreover, significant barriers often exist including access to care and lack of trained providers, that prevent reaching and engagement of individuals to treatments, and there is poor adherence to interventions overall. As such, there is a need to implement interventions and/or complementary approaches that may appeal to Veterans experiencing PTSD-related nightmares who are looking for alternatives. In this regard, NightWare (NW) digital therapeutic is a novel smart watch application that was recently granted Breakthrough Device designation by the FDA for the treatment of nightmares in adults with PTSD. It uses the wearer's biometric data (i.e., heart rate, body movement and position) to distinguish normal and distressed sleep and interrupt nightmares. Preliminary evidence demonstrated an improvement in subjective sleep quality in Veterans after 30-days of NW compared with a sham condition. However, it is unknown whether NW improves sleep quality in Veterans with PTSD with co-morbid medical conditions such as obstructive sleep apnea (OSA) or in those using medications (e.g., prazosin) to treat nightmares related to PTSD. It is also unknown if the effects of NW on sleep are similar in male and female Veterans, or whether improvements in sleep with NW result in improvements in objective sleep (i.e., sleep physiology) or cardiovascular health. In this context, this study will determine if 8 weeks of NW improves subjective sleep in Veterans with PTSD-related nightmares, including those with OSA and/or taking medications to treat PTSD related nightmares (e.g., prazosin). The change in Pittsburgh Sleep Quality Index (PSQI) scores from baseline to 8 weeks will be measured. Additional goals will evaluate changes in cardiovascular health outcomes with NW use and if there are potential sex differences in the response to NW. The proposed research is a high priority topic of the Veterans Affairs, as PTSD affects 11-23% of Veterans in a given year. The research is highly innovative and if successful will lead to significant advances in the healthcare of Veterans, particularly as it relates to the treatment of PTSD-related nightmares.

### Conditions Module

**Conditions:**

- Post-traumatic Stress Disorder (PTSD)

- Cardiovascular Diseases

- Autonomic Dysfunction

- Vascular Stiffness

- Nightmare

- Endothelial Dysfunction

- Veteran

**Keywords:**

- Sleep

- Oxidative stress

- aging, inflammation

- sex/gender

- Veteran

- Trauma and Stressor Related Disorders

- Mental Disorders

- Nervous System Diseases

- Autonomic Nervous System Diseases

- Primary Dysautonomias

- Cardiovascular Diseases

- Stress Disorders, Post-Traumatic

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Randomized, double-blind, placebo (i.e., sham intervention) controlled parallel proof-of-concept study

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 125

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Intervention with NightWare Therapeutic System

**Intervention Names:**

- Device: NightWare

**Label:** NightWare active

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** NightWare app disabled; device will not deliver an intervention

**Intervention Names:**

- Device: NightWare

**Label:** NightWare Sham

**Type:** SHAM_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- NightWare Sham

- NightWare active

**Description:** Nightware intervention app (enabled) will attempt to detect when an individual is having a nightmare based on a Nightware proprietary algorithm and attempt to disrupt the nightmare without awakening. In the sham comparator group the NightWare app will be disabled and not deliver an intervention.

**Name:** NightWare

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Sleep questionnaire with a scale of 0 to 21 with a higher score indicating a significant sleep disturbance

**Measure:** Change in Pittsburgh Sleep Quality Index

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

#### Secondary Outcomes

**Description:** Total sleep duration (minutes) calculated through ambulatory electroencephalography.

**Measure:** Change in physiological sleep - total sleep time

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** Brachial artery flow mediated dilation (FMD) using ultrasound

**Measure:** Change in endothelial function

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** Cardiovagal baroreflex sensitivity (cBRS) measured using beat-to-beat time series of systolic blood pressures (finger photo-plethysmography) and R-R interval (three-lead electrocardiogram) will be recorded simultaneously at 1,000 Hz.

**Measure:** Change in Autonomic function - spontaneous baroreflex sensitivity (BRS)

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** Carotid-femoral pulse wave velocity (PWV)

**Measure:** Change in large elastic artery stiffness

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** Augmentation index and aortic blood pressure via pulse wave analysis

**Measure:** Change in large elastic artery stiffness

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** Heart rate variability

**Measure:** Change in autonomic function - heart rate variability (HRV)

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** Wake after sleep (minutes) calculated through ambulatory electroencephalography.

**Measure:** Change in physiological sleep - wake after sleep onset

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** Sleep efficiency (percentage) calculated through ambulatory electroencephalography.

**Measure:** Change in physiological sleep - sleep efficiency

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** REM sleep (minutes) calculated through ambulatory electroencephalography.

**Measure:** Change in physiological sleep - REM sleep

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** Deep sleep (minutes) calculated through ambulatory electroencephalography.

**Measure:** Change in physiological sleep - Deep sleep

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

**Description:** Light sleep (minutes) calculated through ambulatory electroencephalography.

**Measure:** Change in physiological sleep - Light sleep

**Time Frame:** Measured before and after 8 weeks of NightWare and sham conditions

### Eligibility Module

**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/dL;
6. Poor overall sleep quality as indicated by a Pittsburgh Sleep Quality Index (PSQI) score 6 or higher;
7. Epworth Sleepiness Scale (ESS): Question #8 score above "0" will prompt an additional question: Do you drive ("get behind the wheel") when you are drowsy? The answer must be "No" to be enrolled in the study due to safety concerns;
8. Wireless Internet and two power outlets in sleeping location;
9. 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. Unstable medical condition (e.g., uncontrolled hypertension or active CVD or cancer);
2. Active infection (note, anyone with an active infection would become eligible once the infection has ended);
3. 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;
4. Use of insulin or sulfonylureas
5. Pregnancy or currently breast feeding;
6. Current history (past 3 months) of substance (excluding marijuana) or alcohol abuse per the SCID-5. Adults with past substance or alcohol use disorders will be allowed to participate;
7. Participants will be excluded if they report elevated acute risk for suicidal self-directed violence warranting immediate hospitalization (e.g., suicidal ideation with intent, evaluated by the Columbia-Suicide Severity Rating Scale \[C-SSRS\]).
8. Shift workers (due to circadian rhythm disruption);
9. Diagnosis of active disorder of arousal from non-rapid eye movement sleep, rapid eye movement sleep behavior disorder, or narcolepsy;
10. Nocturia that causes awakening from sleep;
11. Known sleep walking or acting out dreams (contraindication to NW use);
12. Diagnosis or suspicion of dementia;
13. Seizure disorder
14. Participants experiencing severe cognitive impairment or current psychiatric symptoms of such severity that would preclude participation (e.g., active psychosis, imminently suicidal)

**Gender Based:** True

**Gender Description:** All genders

**Healthy Volunteers:** True

**Maximum Age:** 88 Years

**Minimum Age:** 22 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Kerrie.Moreau@va.gov

**Name:** Kerrie L Moreau, PhD

**Phone:** (720) 885-1950

**Role:** CONTACT

**Contact 2:**

**Email:** claire.cox@va.gov

**Name:** Claire Cox, BS

**Phone:** (303) 372-1396

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Aurora

**Contacts:**

***Contact 1:***

- **Email:** claire.cox@va.gov

- **Name:** Claire Cox, BS

- **Phone:** 303-372-1396

- **Role:** CONTACT

***Contact 2:***

- **Name:** Kerrie L Moreau, PhD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Rocky Mountain Regional VA Medical Center, Aurora, CO

**State:** Colorado

**Zip:** 80045

#### Overall Officials

**Official 1:**

**Affiliation:** Rocky Mountain Regional VA Medical Center, Aurora, CO

**Name:** Kerrie L Moreau, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000068099

- Term: Trauma and Stressor Related Disorders

- ID: D000001523

- Term: Mental Disorders

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC26

- Name: Wounds and Injuries

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: BC10

- Name: Nervous System Diseases

### Condition Browse Module - Browse Leaves

- ID: M17685

- Name: Wounds and Injuries

- Relevance: LOW

- As Found: Unknown

- ID: M10293

- Name: Inflammation

- Relevance: LOW

- As Found: Unknown

- ID: M24916

- Name: Stress Disorders, Traumatic

- Relevance: HIGH

- As Found: Traumatic Stress Disorder

- ID: M16103

- Name: Stress Disorders, Post-Traumatic

- Relevance: HIGH

- As Found: Post Traumatic Stress Disorder (PTSD)

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M222

- Name: Trauma and Stressor Related Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4643

- Name: Autonomic Nervous System Diseases

- Relevance: HIGH

- As Found: Autonomic Dysfunction

- ID: M27979

- Name: Primary Dysautonomias

- Relevance: HIGH

- As Found: Autonomic Dysfunction

### Condition Browse Module - Meshes

- ID: D000001342

- Term: Autonomic Nervous System Diseases

- ID: D000054969

- Term: Primary Dysautonomias

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000040921

- Term: Stress Disorders, Traumatic

- ID: D000013313

- Term: Stress Disorders, Post-Traumatic

### Misc Info Module

- Version Holder: 2024-05-31
