REVEAL Study - Diagnostic Testing for PTSD Using the Senseye Diagnostic Tool

Diagnostic Testing of Post-Traumatic Stress Disorder (PTSD) Using the Senseye Diagnostic Tool in Adults : United States, Australia, and Decentralized Trial (DCT) Protocol

The goal of the REVEAL PTSD study is to test how well the Senseye DT works as a diagnostic test for Post-traumatic Stress Disorder (PTSD) in adults 18 and older who are experiencing one or more symptoms that might be related to PTSD.

The Senseye DT is software as a medical device (SaMD) and is an iPhone app that administers a series of simple tasks on the phone while recording video during the tasks through the front-facing camera. The videos are analyzed by a an Artificial Intelligence (AI) algorithm to identify physiologic signals that might be indicative of PTSD. Data collected in this study will be used to train and tune the AI algorithm, then test it for accuracy.

The main questions this study aims to answer are:

1. How accurate is the Senseye DT in detecting PTSD compared to structured clinical interviews, the current clinical standard for diagnostic testing?
2. How accurately does the Senseye DT predict PTSD severity?
3. How fast is the Senseye DT to use compared to structured clinical interviews?

Participants will attend a virtual screening visit via video call to determine eligibility and consent to participate. Once enrolled, participants will attend 2 or 3 additional study visits:

• Visit 1: A virtual visit where standard mental health assessments will be given by clinical raters trained in mental health and administering these structured clinical interviews. These assessments include the Structured Interview Guide for the Montgomery-Asburg Depression Rating Scale (SIGMA), the Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A), and the MINI International Neurodiagnostic Interview. The Clinician-Administered PTSD Scale for DSM-5 Revised Version (CAPS-5-R) may also be conducted, if randomly selected.
• Visit 2: A visit to use the Senseye DT. For participants near one of the study's physical site locations, this visit will be done in person at the site. For all others, this visit will be conducted virtually.
• Visit 3: For participants not randomly selected to have the CAPS-5-R administered at Visit 1, a third and final visit will be scheduled for this assessment. This visit will be conducted virtually.

The total expected participation time for enrolled participants is 6-7 hours over the course of 2-3 weeks.

Inclusion Criteria:

1. The participant is willing and able to read, understand, and sign the approved Informed Consent Form (ICF).

2. Age 18 years old or older.

3. In the past month, participant presents with at least one of the following:

   • nightmares or unwanted, intrusive thoughts
   • avoidance of specific thoughts or situations
   • feelings of being constantly on guard, watchful, or easily startled
   • feeling numb or detached from people, activities, or surroundings; and/or
   • persistent feelings of guilt or self blame for things that have happened.
   • excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance)
   • sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep)
   • depressed mood: most of the day, nearly every day, feeling sad, empty, or hopeless
   • markedly diminished interest or pleasure in activities: loss of interest or pleasure in most activities, nearly every day
   • self-report of significant weight loss or gain and/or changes in appetite
   • insomnia or hypersomnia: sleeping too little or too much
   • psychomotor agitation or retardation: observable restlessness or slowed movements
   • abnormal fatigue or loss of energy: feeling tired or lacking energy more than usual

4. Deemed likely to comply with the study protocol by the study team, including willing communication of adverse events (AEs), mental health history, current and past psychiatric medication & treatments, and ability to attend all study visits.

5. Participant agrees to provide emergency contact information at Screening Visit and their physical location at each visit (if they are joining the visit remotely).

6. Participant is psychologically stable as determined by the investigator or delegate.

7. Participant has access to the following:

   • a device with stable internet and Wi-Fi connection capable of supporting video calls (e.g., tablet, computer with webcam, etc.)
   • a second smart device that must be an iPhone 13 or newer (Not inclusive of the iPhone13 Mini)

8. Participant home/environment meets criteria for Senseye DT setup (remote visits only)

Exclusion Criteria:

1. Current diagnosis of epilepsy and/or other seizure disorders.

2. A history of at Screening OR positive at Visit 1 for bipolar I or II, mania, or one or more schizophrenia-spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, delusional disorder, psychotic depression, and psychosis.

3. Compromised facial neuro-ophthalmic integrity (e.g., due to stroke, MS, ALS, or other neurological conditions).

4. Current diagnosis of dementia, delirium, amnestic disorders, autism, hydrocephalus, posterior cortical atrophy, aphasia, multiple sclerosis, or stroke-related cognitive dysfunction.

5. Current eye disorders which prevent the patient from using the Senseye DT:

   • Vision impairment preventing ability to read with correction (including corneal disease, dense cataract, diabetic retinopathy, macular degeneration, glaucoma, etc.).
   • Use of corrective lenses including glasses and contacts is permitted. Colored contacts and cosmetic lenses that obscure or enhance the pupil are not permitted.
   • Significant eye lid droop blocking the pupil.
   • Persistent blurry vision, headaches, and/or light sensitivity resulting from conditions including abnormal pupil dilation or reactivity (e.g, mydriasis).
   • Recent eye surgeries (within 2 weeks) or planned eye surgeries within the study duration.
   • Intraocular inflammation, including iritis and anterior uveitis.
   • Ocular trauma resulting in uncorrected or permanent bilateral damage.

6. Active suicidal and/or homicidal intent or other self-injurious behavior which may put the participant and/or others at risk per the investigator's clinical judgement, or has suicidal ideation of level 4 or 5 as determined by the C-SSRS.

7. Suicidal behavior within the last year as determined by the C-SSRS at the time of screening.

8. Significant suicidal ideation within the last 6 months as determined by ideation of level 4 or 5 by the C-SSRS at the time of screening.

9. Current reported usage (within 2 weeks of Screening Visit and/or planned ongoing usage during the study) of psychotropic drugs and/or non-psychotropic drugs or medication which may affect use of the Senseye DT:

   • Narcotics/opioids (e.g., Heroin, Vicodin, oxycodone, codeine, Tramadol, etc.).
   • Tricyclic antidepressants (TCAs) (e.g., Tofranil, Pamelor, amitriptyline, doxeprin, etc.).
   • Monoamine Oxidase Inhibitors (MAOIs) (e.g., Emsam, Parnate, Nardil, Marplan, etc.).
   • Select antihypertensive medications (alpha-2 receptor agonists, clonidine, peripheral adrenergic inhibitors, Alpha & Beta blockers, and Rauwolfia alkaloids). Note: If Prazosin can be abstained from for > 24 hours prior to the Senseye DT visit, the exclusion does not apply for that medication.

   Stimulants (e.g., Amphetamines, Ritalin, Focalin, pseudoephedrine/Sudafed, ecstasy, cocaine, methamphetamines, cathinones, etc.). Note: Caffeine or nicotine use is not exclusionary. Note: that if Sudafed, pseudoephedrine, and stimulants commonly used to treat ADHD (e.g., Ritalin, Focalin, Adderall, etc. can be abstained from for > 24 hours prior to the Senseye DT visit, the exclusion does not apply for those medications.

   • Psychedelics/psychotomimetics (Lysergic acid, psilocybin, mescaline, phencyclidine, methoxetamine, etc.).
   • Cholinergic or anticholinergic agents (e.g., Urecholine, Pilocar, Aricept, Miostat, Evoxac, ipratropium/Atrovent, oxybutynin/Ditropan, scopolamine, etc.), except antihistamines other than Benadryl or diphenhydramine. Note: If Benadryl/diphenhydramine can be abstained from for > 24 hours prior to the Senseye DT visit, the exclusion does not apply.
   • Spravato or Ketamine.
   • Eye drops unless the participant is able to abstain from use for > 72 hours prior to the Senseye DT visit. Note: Artificial tears can be used if needed during the Senseye DT use.
   • Central Nervous System (CNS) depressants (Benzodiazepines and Barbiturates)

10. Current reported usage (within 2 weeks of Screening Visit and/or planned ongoing usage during the study) of vagal nerve stimulation, deep brain stimulation, transcranial magnetic stimulation, or other stimulation or energy-based therapies.

11. Any condition which precludes the ability for patients to safely and accurately complete clinical assessments, questionnaires, or to follow instructions necessary to administer the Senseye DT (e.g., significant developmental disabilities, language disorders, cognitive deficiencies, or other neurodevelopmental disorders).

12. Medical diagnosis of Traumatic Brain Injury (TBI) within the last 12 months based on participant self-report.

13. Lifetime history of any of the following: surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's Disease, Parkinson's Disease), or any other disease/procedure/accident/intervention that, according to the clinician, is deemed associated with significant injury to, or malfunction of, the CNS.

14. Involved in active litigation related to the participant's psychiatric symptoms

15. Pregnancy as determined by self-report.

16. Currently incarcerated.

17. Participant requires a legal authorized representative to consent.

18. Prior enrollment in this study or in other Senseye Machine Learning (ML) studies within the last 12 months.

19. Unwilling or unable to comply with all study related procedures, in the opinion of the investigator, including medical and non-medical procedures.