ACE-D Aim 3 Clinical Cognitive Trial to Enhance Translation in Depression

NCT06408246 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2025-1145
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to understand how a psychotropic medication called guanfacine affects brain network functioning in humans, and how this function interacts with cognitive impairments in people experiencing depressive symptoms.

Conditions

Depression

Keywords

Precision Psychiatry; Depression; Cognitive Symptoms

Outcome Measures

Primary Outcomes (1)

• Remission of depressive symptoms

  A score of \<=5 on the PHQ-9

  8 weeks

Secondary Outcomes (2)

• Change in disability

  8 weeks

• Change in quality of Life

  8 weeks

Study Arms (2)

Sertraline + Guanfacine

EXPERIMENTAL

We will conduct a parallel-group, double-blind randomized trial at Stanford Bay Area and Chicago sites, identifying 160 participants with a prominent clinical cognitive signature (C+) and relative absence of the signature (C-). We will enrich for C+, the signature of interest, at a 2:1 ratio. Participants will be randomly assigned to receive guanfacine (shown to ameliorate cognitive control deficits in our preliminary data) plus sertraline or placebo plus sertraline.

Drug: Guanfacine

Sertraline + Placebo

EXPERIMENTAL

We will conduct a parallel-group, double-blind randomized trial at Stanford Bay Area and Chicago sites, identifying 160 participants with a prominent clinical cognitive signature (C+) and relative absence of the signature (C-). We will enrich for C+, the signature of interest, at a 2:1 ratio. Participants will be randomly assigned to receive guanfacine (shown to ameliorate cognitive control deficits in our preliminary data) plus sertraline or placebo plus sertraline.

Drug: Sertraline

Interventions

Guanfacine DRUG

Guanfacine immediate release is an established and safe FDA-approved treatment that acts directly by stimulating α2A adrenoceptors.

Sertraline + Guanfacine

Sertraline DRUG

Sertraline is a well-tolerated FDA-approved antidepressant that is among the most widely prescribed medications for depression.

Sertraline + Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and lifestyle considerations (see Section 5.3) and availability for the duration of the study
• Male or female
• Age 18-60 years
• Fluent and literate in English
• Meets DSM-5-TR diagnostic criteria for MDE (major depressive episode), and criteria for current or recurrent nonpsychotic MDD using the Mini International Neuropsychiatric Interview (MINI Plus)79
• A total score of 10 or higher on the PHQ-8 at initial screening, including:
• a. Endorsement of anhedonia, as indexed by a response of "more than half the days" or "nearly every day" to Item 1 ("Little interest or pleasure in doing things") or endorsement of persistent negative mood, as indexed by a response of "more than half the days" or "nearly every day" to Item 2 ("Feeling down, depressed, or hopeless")
• Meets criteria for cognitive dysfunction (C+ subgroup) or absence of cognitive dysfunction (C- subgroup) based on results from computerized behavioral testing of cognitive control performance (WebNeuro) and from fMRI scanning using the Go/No-Go task.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Presence of one or more of the following conditions established via the participant's medical record and confirmed using the MINI Plus:
• bipolar disorder (I, II, not otherwise specified, current or lifetime)
• psychosis (current or lifetime)
• moderate to severe alcohol or substance use disorders (current)
• post-traumatic stress disorder (PTSD; current)
• obsessive compulsive disorder (OCD; current or lifetime)
• attention deficit hyperactivity disorder (ADHD; current or lifetime)
• eating disorders (ED; current)
• Suicidality with active plan
• Severe impediment to vision, hearing, and/or hand movement
• Current or lifetime history of medical illness or brain injury that may interfere with assessments
• Pregnant, breastfeeding, or unwilling or unable to use adequate birth control throughout the study (females of child-bearing potential only)
• T MRI scanner contraindications (e.g., metal in the body, claustrophobia)
• Concurrent participation in other intervention studies

Sponsors & Collaborators

• Stanford University: lead

Study Sites (2)

Stanford Psychiatry and Behavioral Sciences Department

Palo Alto, California, 94305, United States

RECRUITING

University of Illinois at Chicago

Chicago, Illinois, 60607, United States

RECRUITING

MeSH Terms

Conditions

Depression; Neurobehavioral Manifestations

Interventions

Guanfacine; Sertraline

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; 1-Naphthylamine; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Leanne Williams, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leyla Boyar, BA

CONTACT

6504989326; ljboyar@stanford.edu

Isabelle Wydler Clinical Research Coordinator, BA

CONTACT

6507364393; iwydler@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants in C+ and C- subgroups will be randomized to one of two treatment arms

Study Record Dates

• First Submitted: May 6, 2024
• First Posted: May 10, 2024
• Study Start: March 3, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (2)