Investigating brain responses to threats in anxiety and depression

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

This study is testing how an anti-anxiety medication affects the brain's response to threats in people with anxiety, depression, or both to better understand their differences and improve treatments.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 165 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Laureate Institute for Brain Research, Inc. (Academic / other)
• Locations: 1 site (Tulsa, Oklahoma)
• Trial ID: NCT06004115 on ClinicalTrials.gov

What this trial studies

This study examines how the brain processes threats in individuals with anxiety and depression by using an anti-anxiety medication, Lorazepam, and advanced brain imaging techniques. Participants will be divided into three groups based on their mental health diagnoses: those with both major depressive disorder and anxiety, those with only major depressive disorder, and those with only anxiety disorders. Each participant will undergo two experimental sessions involving a startle response task and functional MRI scans to assess their brain activity in response to threats. The goal is to understand the differences in threat sensitivity and brain circuitry among these groups, potentially leading to targeted treatments.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-65 with a diagnosis of major depressive disorder and at least one anxiety disorder.

Not a fit: Patients with uncontrolled significant neurological or medical conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for individuals suffering from co-morbid anxiety and depression.

How similar studies have performed: Previous studies have shown promising results in understanding threat processing in anxiety and depression, making this approach both relevant and potentially impactful.

Eligibility criteria

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

Where this trial is running

Tulsa, Oklahoma

• Laureate Institute for Brain Research — Tulsa, Oklahoma, United States (Recruiting)

Study contacts

• Principal investigator: Maria Ironside, DPhil — Laureate Institute for Brain Research
• Study coordinator: Maria Ironside, DPhil

Conditions Depression, Anxiety; Fear; Depression; Anxiety and Fear; Anxiety Disorders; Anxious Depression; depression; anxiety