ERG Biomarkers for PTSD Treatment

(BRIGHT Trial)

Overseen By Rebecca C Hendrickson, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Puget Sound Health Care System

Must not be taking: Serotonin drugs

Disqualifiers: Psychotic disorder, Glaucoma, Retinal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You will need to stop taking sertraline or other drugs that affect serotonin for at least 6 half-lives before the study and avoid them during the study.

What data supports the effectiveness of the drug Zoloft for PTSD treatment?

Research shows that antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) like Zoloft, are effective in treating PTSD symptoms. Studies indicate that combining medication with psychotherapy can enhance treatment outcomes for PTSD. ^{1 2 3 4 5}

Is the treatment safe for humans?

The treatment, which includes medications like sertraline (also known as Zoloft), is generally considered safe for humans, as it is commonly used and well-tolerated in treating conditions like PTSD. However, more research is needed to confirm its safety specifically for the ERG Biomarkers for PTSD Treatment. ^{1 2 6 7 8}

How does the ERG Biomarkers treatment for PTSD differ from other treatments?

The ERG Biomarkers treatment for PTSD is unique because it uses electroretinography (ERG), a test that measures the electrical activity of the retina, as a potential biomarker to understand and diagnose psychiatric disorders. This approach is novel as it indirectly studies brain function through the retina, which is part of the central nervous system, offering a new way to explore the biological basis of PTSD compared to traditional methods. ^{9 10 11 12 13}

What is the purpose of this trial?

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.

Research Team

Rebecca Hendrickson, MD, PhD

Principal Investigator

VA Puget Sound Health Care System

Eligibility Criteria

This trial is for veterans with PTSD. Participants will have their eye's electrical activity (ERG) measured before and after taking sertraline, an approved medication for PTSD. They must be willing to share their PTSD symptoms and treatment history.

Inclusion Criteria

Veteran of the U.S. Armed Forces

I have been diagnosed with PTSD.

Exclusion Criteria

Known current pregnancy or lactation

I have had acute angle closure glaucoma.

Previous ERG deficits

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo ERG recordings, provide clinical information, and receive a single dose of sertraline

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in ERG waveform and PTSD symptoms after sertraline administration

1 day

1 visit (in-person)

Open-label Extension (optional)

Participants who initiate antidepressant treatment through routine clinical care are invited back for a follow-up ERG recording

Up to 1 year

Treatment Details

Interventions

• RETeval

Trial Overview The study is testing if the ERG, which measures retina signals, can predict how well veterans with PTSD respond to sertraline. It checks changes in the ERG waveform before and after a single dose of the medication.

Participant Groups

Group I: ERG, all participants Experimental Treatment 1 Intervention

All participants undergo ERG recording before and after a single dose of sertraline 50 mg.

Who Is Running the Clinical Trial?

VA Puget Sound Health Care System

Lead Sponsor

Trials

67

Recruited

225,000+

Findings from Research

The PROGrESS trial is a randomized controlled trial designed to compare the effectiveness of psychotherapy (Prolonged Exposure) and medication (Sertraline) for treating PTSD in veterans, utilizing innovative measures to assess treatment response and potential biomarkers.

This study will provide valuable insights into the mechanisms of treatment effectiveness and help guide clinical practices for PTSD by analyzing various outcomes, including genetic factors and brain activity through fMRI, across three treatment conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating biological treatment mechanisms into randomized clinical trials: Design of PROGrESS (PROlonGed ExpoSure and Sertraline Trial). Rauch, SAM., Simon, NM., Kim, HM., et al.[2019]

In a study of 88 PTSD patients, eye movement desensitization and reprocessing (EMDR) therapy was found to be more effective than the SSRI fluoxetine in achieving long-term reductions in PTSD and depression symptoms, especially for adults with trauma experienced in adulthood.

At the 6-month follow-up, 75% of adult-onset trauma patients receiving EMDR reached asymptomatic functioning, while none in the fluoxetine group did, highlighting EMDR's potential as a superior treatment for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance. van der Kolk, BA., Spinazzola, J., Blaustein, ME., et al.[2022]

Citalopram showed potential in alleviating PTSD symptoms in two case studies of Persian Gulf War veterans, indicating its possible efficacy for this condition.

The authors suggest that further controlled studies are needed to confirm citalopram's effectiveness as a treatment option for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical experience of citalopram in the treatment of post-traumatic stress disorder: a report of two Persian Gulf War veterans. Khouzam, HR., el-Gabalawi, F., Donnelly, NJ.[2017]

Tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) have been shown to specifically alleviate symptoms of posttraumatic stress disorder (PTSD), indicating their potential effectiveness as treatment options.

Despite historical recognition of drug and somatic treatments for PTSD, ongoing research is necessary to fully understand and optimize these therapies for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy in posttraumatic stress disorder: historical and clinical considerations and future directions. Davidson, JR., Nemeroff, CB.[2009]

Antidepressants, particularly tricyclics, MAOIs, and SSRIs, have shown significant efficacy in treating both core and secondary symptoms of PTSD, supported by data from double-blind, placebo-controlled trials.

Benzodiazepines have not been effective in controlled trials for PTSD and may cause rebound effects upon discontinuation, while anticonvulsants show moderate to good improvement in small studies, suggesting a need for careful selection of medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapies for posttraumatic stress disorder: an overview. Davidson, JR.[2022]

In an 8-week trial with 14 adult participants suffering from PTSD, citalopram significantly reduced core symptoms such as re-experiencing, hyperarousal, and avoidance, with 9 out of 11 completers classified as 'responders'.

Citalopram was well-tolerated with no dropouts due to adverse effects, suggesting it is a safe option for treating PTSD, although further confirmation through more rigorous trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open trial of citalopram in adults with post-traumatic stress disorder. Seedat, S., Stein, DJ., Emsley, RA.[2019]

Paroxetine is effective for the short-term treatment of PTSD, showing significantly better response and remission rates compared to placebo in three 12-week studies.

The medication improves sleep disturbances and reduces all symptom clusters of PTSD, demonstrating efficacy in both male and female patients, regardless of the presence of comorbid conditions like depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paroxetine in the treatment of post-traumatic stress disorder: pooled analysis of placebo-controlled studies. Stein, DJ., Davidson, J., Seedat, S., et al.[2022]

Antidepressants are generally safe and accessible treatments for PTSD, but there is limited evidence on their effectiveness in improving sleep disturbances associated with the condition, based on a review of 39 randomized controlled trials.

Some antidepressants, such as amitriptyline, nefazodone, paroxetine, and sertraline, may help improve sleep quality in PTSD patients, but more robust studies are needed to confirm these findings and better understand their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Antidepressants on Sleep in Post-traumatic Stress Disorder: An Overview of Reviews. Lappas, AS., Polyzopoulou, ZA., Christodoulou, N., et al.[2023]

Electroretinography (ERG) has shown potential as a diagnostic tool in psychiatry, revealing specific changes in retinal responses associated with conditions like cocaine withdrawal, major depressive disorder, and schizophrenia.

Despite promising findings, current research on ERG's diagnostic utility lacks specificity, indicating a need for further studies to better quantify the retinal anomalies linked to various psychiatric illnesses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electroretinography in psychiatry: A systematic literature review. Youssef, P., Nath, S., Chaimowitz, GA., et al.[2020]

The study identified specific contributions to the multifocal electroretinogram (ERG) from the inner retina in monkeys, using intravitreal injections of NMDLA and TTX to isolate these components.

Similar waveform components were observed in human multifocal ERG recordings at lower stimulus contrasts (50%), but were diminished or absent in patients with glaucoma and diabetes, indicating potential biomarkers for inner retinal dysfunction in these diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying inner retinal contributions to the human multifocal ERG. Hood, DC., Greenstein, V., Frishman, L., et al.[2022]

The flash electroretinogram (ERG) can be a useful tool for indirectly studying brain functions, as it measures retinal responses that may reflect central nervous system dysfunctions associated with psychiatric disorders.

Anomalies in flash ERG have been observed in various psychiatric conditions, including seasonal affective disorder, schizophrenia, autism spectrum disorder, and drug addiction, suggesting that retinal function changes could serve as potential biomarkers for these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The brain through the retina: the flash electroretinogram as a tool to investigate psychiatric disorders. Lavoie, J., Maziade, M., Hébert, M.[2015]

The RETeval™ device showed high intra-visit reliability for measuring 30-Hz flicker ERG amplitudes in children under 3 years old undergoing vigabatrin treatment, with ICC values of 0.81 and 0.86 for the right and left eyes, respectively.

RETeval™ ERG responses were positively associated with standard Espion ERG results, indicating that it can effectively monitor retinal health and potential toxicity in young patients receiving vigabatrin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hand-held, dilation-free, electroretinography in children under 3 years of age treated with vigabatrin. Ji, X., McFarlane, M., Liu, H., et al.[2020]

Chlorpromazine (CPZ), an antidopaminergic drug, significantly prolonged the latencies of mixed and cone electroretinograms (ERGs) and reduced the amplitudes of rod- and cone-dominated ERGs in a study involving 15 normal volunteers.

The study found that CPZ also delayed the peaks of pattern-reversal visual evoked potentials (P-VEP) and pattern ERGs (P-ERG), indicating that CPZ primarily affects retinal electrophysiology, while oxazepam (OZP) showed minimal effects compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of chlorpromazine on pattern and flash ERGs and VEPs compared to oxazepam and to placebo in normal subjects. Bartel, P., Blom, M., Robinson, E., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Integrating biological treatment mechanisms into randomized clinical trials: Design of PROGrESS (PROlonGed ExpoSure and Sertraline Trial). [2019]

2. United States pubmed.ncbi.nlm.nih.gov

A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The clinical experience of citalopram in the treatment of post-traumatic stress disorder: a report of two Persian Gulf War veterans. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Pharmacotherapy in posttraumatic stress disorder: historical and clinical considerations and future directions. [2009]

5. United States pubmed.ncbi.nlm.nih.gov

Biological therapies for posttraumatic stress disorder: an overview. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Open trial of citalopram in adults with post-traumatic stress disorder. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Paroxetine in the treatment of post-traumatic stress disorder: pooled analysis of placebo-controlled studies. [2022]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effects of Antidepressants on Sleep in Post-traumatic Stress Disorder: An Overview of Reviews. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Electroretinography in psychiatry: A systematic literature review. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Identifying inner retinal contributions to the human multifocal ERG. [2022]

11. England pubmed.ncbi.nlm.nih.gov

The brain through the retina: the flash electroretinogram as a tool to investigate psychiatric disorders. [2015]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Hand-held, dilation-free, electroretinography in children under 3 years of age treated with vigabatrin. [2020]

13. Ireland pubmed.ncbi.nlm.nih.gov

Effects of chlorpromazine on pattern and flash ERGs and VEPs compared to oxazepam and to placebo in normal subjects. [2019]