Processes and Circuitry Underlying Threat Sensitivity as a Treatment Target for Co-morbid Anxiety and Depression

Processes and Circuitry Underlying Threat Sensitivity as a Treatment Target for Co-morbid Anxiety and Depression (NCT06004115) is a Phase 4 interventional studying Depression, Anxiety and Fear, sponsored by Laureate Institute for Brain Research, Inc.. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

This mechanistic study uses an anti anxiety drug and brain imaging to study the threat processing system and associated brain circuits in people with depression, anxiety disorders and comorbid depression and anxiety disorders. In a double blind, placebo controlled crossover design, up to 65 individuals will be recruited who will have a diagnosis of major depressive disorder (MDD) and at least one anxiety disorder (AD) (AD-MDD group), up to 65 participants will have a diagnosis of MDD and no diagnosis of an AD and up to 65 participants will have no diagnosis of MDD and a diagnosis of at least one AD will be enrolled to participate in an two session study to obtain 150 completers (50 per group). All participants will receive a single dose of Lorazepam and placebo (order randomized) taken orally. After the \~2.5 hr screening session, participants will complete two identical \~5 hr experimental sessions, each of which include a 30 min eyeblink startle session and a 1.5 hr functional magnetic resonance imaging (MRI) brain scan session. The total time involved in the study is approximately 10.5 hours. The main questions the study seeks to answer are: * are people with comorbid depression and anxiety different than those with depression alone in terms of their eyeblink startle response to threat? * are people with comorbid depression and anxiety different than those with depression alone in terms of their brain activation in response to threat? * are people with comorbid depression and anxiety different than those with depression alone in terms of their responses to anxiety drugs?

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 165 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Depression, Anxiety subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

An individual must meet the following criteria to be considered eligible to participate in the study: Who May Qualify: All subjects: - Female or male sex assigned at birth; - Age 18-65; - Normal or corrected to normal vision/hearing, as protocol elements may not be valid otherwise; - Fluent English speaker, capable of providing written willing to sign a consent form MDD and AD-MDD subjects: - Current major depressive episode assessed by clinician with guidance from the MINI; - Minimum score of 55 on PROMIS Depression scale AD and AD-MDD subjects: - Current anxiety disorder (generalized anxiety disorder, panic disorder, agoraphobia and social phobia) assessed by clinician with guidance from the MINI; - Minimum score of 55 on PROMIS Anxiety Scale Who Should NOT Join This Trial: All subjects: - Has uncontrolled, clinically significant neurologic (including seizure disorders): cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the subject to participate or potentially confound the study results; - Reported body mass index (BMI) \> 40; - History of moderate or severe traumatic brain injury, as assessed by a TBI questionnaire; - History of eating disorder or obsessive-compulsive disorder, schizophrenia, schizo-affective disorder, bipolar disorder or any sign of psychosis; - Current post-traumatic stress disorder (PTSD) diagnosis (although history of trauma is allowed); ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

An individual must meet the following criteria to be considered eligible to participate in the study: Inclusion Criteria: All subjects: * Female or male sex assigned at birth; * Age 18-65; * Normal or corrected to normal vision/hearing, as protocol elements may not be valid otherwise; * Fluent English speaker, capable of providing written informed consent MDD and AD-MDD subjects: * Current major depressive episode assessed by clinician with guidance from the MINI; * Minimum score of 55 on PROMIS Depression scale AD and AD-MDD subjects: * Current anxiety disorder (generalized anxiety disorder, panic disorder, agoraphobia and social phobia) assessed by clinician with guidance from the MINI; * Minimum score of 55 on PROMIS Anxiety Scale Exclusion Criteria: All subjects: * Has uncontrolled, clinically significant neurologic (including seizure disorders): cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the subject to participate or potentially confound the study results; * Reported body mass index (BMI) \> 40; * History of moderate or severe traumatic brain injury, as assessed by a TBI questionnaire; * History of eating disorder or obsessive-compulsive disorder, schizophrenia, schizo-affective disorder, bipolar disorder or any sign of psychosis; * Current post-traumatic stress disorder (PTSD) diagnosis (although history of trauma is allowed); * Current use of medications with major effects on brain function or the fMRI hemodynamic response (e.g., methylphenidate, acetazolamide, excessive caffeine intake \> 1000 mg/day) following an initial list compiled by LIBR but also assessed on a case-by-case basis. Individuals who are currently on medication (antidepressants such as SSRIs, TCAs, SNRIs, and Bupropion) and who have not undergone dose or medication changes over the past 6 weeks will be allowed to participate; * Current benzodiazepine or opiate use; * Moderate to severe current substance use disorder, defined as 5 or more symptoms of the criteria for Substance Use Disorder according to DSM 5; * Drug or alcohol intoxication (based on positive UTOX or breathalyzer test at screening or study session) or reported alcohol/drug withdrawal, last cannabis use must be \>48 hours prior to study session; * Has a risk of suicide according to the Investigator's clinical judgement or per Columbia-Suicide Severity Rating Scale (C-SSRS) or equivalent PhenX instrument, the subject scores "yes" on items 4 or 5 in the Suicidal Ideation section with referent to a 30-day period prior to Screening/Baseline or the subject has had one or more suicidal attempts with reference to a 2-year period prior to Screening; * MRI contraindications; * Is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during this time-period; * Any subject judged by the Investigator to be inappropriate for the study. MDD subjects: * Current (assessed by clinician with guidance from the MINI) anxiety disorder; * Score of \> 60 on PROMIS Anxiety Scale AD subjects: * Current or past recurrent major depressive episodes assessed by clinician with guidance from the MINI; * Score of \> 60 on PROMIS Depression scale

Treatments Being Tested

DRUG

Lorazepam

1mg of Lorazepam will be prepared by pharmacy (Barnes, Tulsa) in capsule form

OTHER

Placebo

placebo will be prepared by pharmacy (Barnes, Tulsa) in capsule form

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Laureate Institute for Brain Research

Tulsa, Oklahoma, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06004115), the sponsor (Laureate Institute for Brain Research, Inc.), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06004115 clinical trial studying?

Who can participate in NCT06004115?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06004115?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06004115. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06004115. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.