The BIomarker Guided Study for Depression

• Status: Not yet recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The diagnosis of major depression relies on patient reports, and two patients with the same diagnosis might share only one symptom. Thus, a single mechanism is unlikely to underlie a broad descriptive diagnosis such as major depression. Our approach is anchored by a neural circuit taxonomy that proposes distinct biotypes of depression derived from functional magnetic resonance imaging (fMRI) (Williams et al., 2016). In this study, we aim to target a putative type of major depression that arises from dysfunction in cognitive control neural circuitry with a drug called guanfacine.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stanford University
• Treatments: Guanfacine

Criteria

Inclusion Criteria:

• 18-65 years of age (inclusive)

• DLPFC activity in the upper or lower quartile as compared to a normative sample

• Working memory performance <= 1 SD below the mean of a normative sample on the Verbal Memory, Digit Span, or Maze tasks.

• Score > 14 on the Hamilton Depression Rating Scale 17

• Meet DSM-5 diagnostic criteria for current, past, or recurrent nonpsychotic major depressive disorder established by MINI Plus

• Medication naïve to guanfacine

• Fluent and literate in English, and show non-impaired intellectual abilities to ensure adequate comprehension of the task instructions

• Written, informed consent

• fMRI scanning eligibility, including no evidence of any form of metal embedded in the body (e.g., metal wires, nuts, bolts, screws, plates, sutures), as these produce artifacts when brain imaging. All potential subjects will need to successfully complete the screening forms at the Stanford Center for Cognitive and Neurobiological Imaging (CNI).

Exclusion Criteria:

• Presence of suicidal ideation representing imminent risk, defined by a score of > 8 on the MINI Plus International Neuropsychiatric Schedule, or by clinician judgement

• Lifetime history of medical illness or injury that may compromise cognitive functioning or interfere with assessments (including neurological disorders such as seizures or stroke, Parkinson's disease, dementia, mild traumatic brain injury)

• Severe impediment to vision, hearing and/or hand movement, likely to interfere with ability to complete the assessments, or are unable and/or unlikely to follow the study protocols

• Pregnant, breastfeeding or unwilling or unable to use adequate birth control throughout the study

• Any contraindication to being scanned in the 3.0T scanner at the CNI such as having a pacemaker or implanted device that has not been cleared for scanning at 3.0 Tesla

• History of DSM-5 bipolar disorder (I, II, not otherwise specified), eating disorder, ADHD, schizophrenia, schizoaffective disorder, or psychosis not other specified (current or lifetime)

• History of DSM-5 alcohol or substance use disorder criteria within the last 12 months

• Meeting criteria for current DSM-5 PTSD or OCD

• Concurrent participation in other intervention or treatment studies

• Current use of psychotropic medications. If their usual treating physician is supportive, participants who are currently on psychotropics that can be safely tapered may be tapered off to participate but participant must wait 5 half-lives of the prescribed drug prior to first scan.

• General medical condition, disease or neurological disorder that is deemed by the study physicians to be unsafe for GIR treatment (kidney or liver impairment, hypotension, bradycardia, history of syncope, or family history of cardiac events)

• Positive drug screen for any substance deemed by the study physician to be unsafe for use with GIR in combination with other information obtained during screening

• Current use of a strong CYP3A4 inhibitor or inducer