Biomarkers in the Retina for Prognosticating Mental Health Treatments (BRIGHT)

Electroretinogram (ERG) as a Potential Biomarker of Serotonin Selective Reuptake Inhibitor (SSRI)-Responsive Posttraumatic Stress Disorder (PTSD): A Pilot Study

Title: ERG as a potential biomarker of SSRI-responsive PTSD: A pilot study

Posttraumatic stress disorder (PTSD) affects many individuals who experience a traumatic event. Previous studies suggest that there is a connection between the brain and the retina, and that the electroretinogram (ERG) may be a valuable biomarker to tell us more about signals in the brain that are related to mental health disorders like PTSD. The goal of this observational study is to examine the ERG waveform in veterans with PTSD before and after a single dose of the selective serotonin reuptake inhibitor (SSRI), sertraline. Sertraline is one of two FDA-approved medications for the treatment of PTSD. The main questions this pilot study aims to answer are:

1. How does sertraline, an SSRI, influence the ERG waveform in veterans with PTSD?
2. Is there a significant correlation between baseline ERG signals and the change in ERG following SSRI treatment?

Participants will be asked to:

• Undergo ERG recordings before and after a single dose of sertraline.
• Provide relevant clinical information related to PTSD symptoms and treatment history.

Following the initial study visits, participants will enter an optional open label phase of the study in which qualifying participants who initiate antidepressant treatment through routine clinical care will be invited back for a follow-up ERG recording.

Study Overview

• Status: Recruiting
• Conditions: PTSD; Posttraumatic Stress Disorder
• Intervention / Treatment: Device: RETeval

Detailed Description

In this study, individuals will undergo an assessment that includes taking a history of their previous exposure to traumatic events, an assessment of current mental health symptoms including those associated with PTSD, and an assessment of physiologic measures, including ERG as well as vital sign measurements, blood draw, and saliva sampling. Participants will be given a single dose of sertraline (50mg), and a repeat ERG will be administered. An optional open label phase of the study will follow, in which participants who undergo treatment with an antidepressant will be invited back for a follow-up assessment with repeat ERG.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katharine J Liang, MD, PhD; Phone Number: (206) 277-6538; Email: katharine.liang@va.gov
• Study Contact Backup: Name: Rebecca C Hendrickson; Phone Number: 206-277-5054; Email: rebecca.hendrickson@va.gov

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98108
      • Recruiting
      • VA Puget Sound Health Care System
      • Contact: Rebecca C Hendrickson, MD, PhD; Phone Number: 206-277-5054; Email: rebecca.hendrickson@va.gov
      • Sub-Investigator: Katharine J Liang, MD, PHD
      • Principal Investigator: Rebecca C Hendrickson, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Veteran of the U.S. Armed Forces
• Current diagnosis of PTSD

Exclusion Criteria:

• Known diagnosis of a primary psychotic or major neurocognitive disorder
• Significant bilateral visual loss
• History of acute angle closure glaucoma
• Known inherited retinal disease
• Previous ERG deficits
• Known photosensitive epilepsy
• Known current pregnancy or lactation
• Allergy or previous adverse reaction to sertraline or SSRI
• Allergy to Sensor Strip gel
• Hepatic failure
• Damage to orbit structure or open lesion in soft tissue surrounding the eye
• Any use in the time period of at least 6 half-lives prior to baseline of sertraline or other drugs acting on serotonin and/or unwillingness to avoid these medications for the duration of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ERG, all participants; All participants undergo ERG recording before and after a single dose of sertraline 50 mg.	Device: RETeval; as previous; Other Names: electroretinogram; ERG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ERG b-wave amplitude response to SSRI	The change in b-wave amplitude following a single dose of sertraline compared to baseline b-wave amplitude will be calculated. The relationship between baseline b-wave amplitude and change in b-wave amplitude will be analyzed.	ERGs will be performed at the baseline visit prior to a single dose of sertraline, and again after sertraline the following day. ERG will also be performed at the follow up visit for a subset of participants who qualify, up to 1 year following baseline.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Clinician Administered PTSD Scale for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; CAPS-5) score	CAPS-5 administered at baseline	PTSD measures will be collected as a part of the baseline assessment. CAPS-5 will also be readministered at the follow up visit for a subset of participants who qualify, up to 1 year following baseline.
Total PTSD Checklist for DSM-5 (PCL-5)	Self report PTSD Checklist (PCL-5) administered at baseline	PTSD measures will be collected as a part of the baseline assessment. PCL-5 will also be repeated at the follow up visit for a subset of participants who qualify, up to 1 year following baseline.

Collaborators and Investigators

• Sponsor: VA Puget Sound Health Care System
• Investigators: Principal Investigator: Rebecca Hendrickson, MD, PhD, VA Puget Sound Health Care System

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: March 18, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: PTSD; SSRI; antidepressant; serotonin; posttraumatic stress disorder; electroretinogram; ERG
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: 1743326

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes