DepressionPhase 2ACE-DNCT06408246
ACE-D Aim 3 Clinical Cognitive Trial to Enhance Translation in Depression
A Phase 2 study testing Guanfacine and Sertraline in people with Depression, run by Stanford University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Depression
- What is being tested?
- Guanfacine and Sertraline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 162 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Mar 2026to 1 Feb 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 10Show fewer
- 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:
- 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.
Who cannot join
- 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)
Show all 35Show fewer
- 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)
- 3.0T MRI scanner contraindications (e.g., metal in the body, claustrophobia)
- Concurrent participation in other intervention studies
- Current use of psychotropic medications contraindicated by guanfacine or sertraline
- General medical condition or disorder that is deemed by study physicians to be unsafe for GIR as reported by patient or found on medical screening. This may include:
- Cardiac-related exclusions:
- Resting heart rate (HR) < 55 beats per minute (bradycardia)
- Systolic blood pressure (SBP) < 90 mmHg or diastolic blood pressure (DBP) < 60 mmHg (hypotension)
- Current symptoms suggestive of cardiac dysfunction based on clinician assessment (e.g., persistent chest pain, palpitations, dizziness, fainting)
- Renal-related exclusions:
- eGFR < 60 mL/min/1.73 m²
- Current symptoms suggestive of kidney dysfunction based on clinician assessment
- Hepatic-related exclusions:
- ALT > 2× ULN
- AST > 2× ULN
- Current symptoms suggestive of liver dysfunction based on clinician assessment
- Thyroid-related exclusions:
- TSH outside normal laboratory reference range
- Current symptoms suggestive of thyroid dysfunction based on clinician assessment
- Use of substance deemed by the study physician to be unsafe for use with guanfacine
- Current use of a strong CYP3A4 inhibitor (e.g., ketoconazole) or inducer (e.g., carbamazepine) that, in the judgment of the study clinician, may alter guanfacine plasma concentrations and cannot be safely discontinued for the duration of the study.
- Unwillingness to verify biotype classification via fMRI
- Unwillingness or inability to use a computer or access a computer for assessments.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Illinois at Chicago
Chicago, Illinois, 60607
Jun Ma, PhD
Jun Ma, PhD
- Recruiting
Stanford Psychiatry and Behavioral Sciences Department
Palo Alto, California, 94305
About this study
Official title: Accelerating Cognition-guided Signatures to Enhance Translation in Depression Aim 3: Clinical Cognitive Trial
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.
Read the detailed description
The investigators will conduct a parallel-group, double-blind randomized trial at Stanford Bay Area and Chicago sites, identifying 162 participants across Stanford University and the University of Illinois Chicago with a prominent clinical cognitive signature (C+) and relative absence of the signature (C-).
If you are eligible and choose to participate based off of your answers on the screening survey, the investigators will call you on the number you have provided to verify participants' responses and answer any additional questions you may have about the study.
The first screening visit will consist of obtaining participants' informed consent to participate in the study, completing cognitive testing, answering questions about participants' thoughts and feelings, and providing information about participants' medical and psychiatric history.
If participants are deemed eligible at this phase, the investigators will ask participants to come in for an in-person medical screening (up to 2 hours). This in-person medical screen visit will consist of getting your vitals taken (heart rate/blood pressure), undergoing a blood draw, and providing a urine sample. Additionally, people who are or suspect they may become pregnant throughout the course of the study will be given a pregnancy test.
If a participant is deemed eligible after the medical screen, the investigators will ask participants to come in for another in-person visit (2 hours) that would involve a non-invasive brain scan. Participants will then be randomized to receive guanfacine plus sertraline or placebo plus sertraline for an 8 week treatment phase.
Starting week 1 and for every week during the 8-week treatment phase, participants will complete nightly medication log surveys, passive sampling with the BiAffect application, and conduct cognitive testing. Additionally, starting week 1 and every week thereafter, participants will attend a virtual physician visit. At the end of week 8, the investigators will conduct an MRI visit that resembles the initial MRI visit. Participants will be unblinded over weeks 9-10 to arrange for the participants' transition out of the trial.
- Conditions
- Depression
- Being tested
- Guanfacine, Sertraline
- Keywords
- Precision Psychiatry, Depression, Cognitive Symptoms
- Medical subject headings
- Depression, Neurobehavioral Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GuanfacineDrug
Guanfacine immediate release is an established and safe FDA-approved treatment that acts directly by stimulating α2A adrenoceptors.
SertralineDrug
Sertraline is a well-tolerated FDA-approved antidepressant that is among the most widely prescribed medications for depression.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Sertraline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission of depressive symptoms
A score of <=5 on the PHQ-9
Measured: 8 weeks
Secondary outcomes (2)
Change in disability
Score on the Sheehan Disability Scale which ranges from 0 to 30
Measured: 8 weeks
Change in quality of Life
Score on the Short Form 8 Health Survey (SF-8) which ranges from 0 to 100
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2024
- Study start3 Mar 2026
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants in C+ and C- subgroups will be randomized to one of two treatment arms
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 162 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Leanne Williams, Stanford University
- Investigators
- Leanne Williams, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06408246
- Sponsor's protocol ID
- 2025-1145
- Acronym
- ACE-D
- Status last verified
- Mar 2026
- First submitted
- 6 May 2024
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Accelerating Cognition-guided Signatures to Enhance Translation in Depression Aim 3: Clinical Cognitive Trial
- ClinicalTrials.gov ID
- NCT06408246
- Acronym / sponsor ID
- ACE-D / 2025-1145
- Conditions
- Depression
- Keywords
- Precision Psychiatry, Depression, Cognitive Symptoms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 162 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 3 Mar 2026 (actual)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Feb 2029 (estimated)
- First posted
- 10 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The investigators will conduct a parallel-group, double-blind randomized trial at Stanford Bay Area and Chicago sites, identifying 162 participants across Stanford University and the University of Illinois Chicago with a prominent clinical cognitive signature (C+) and relative absence of the signature (C-).
If you are eligible and choose to participate based off of your answers on the screening survey, the investigators will call you on the number you have provided to verify participants' responses and answer any additional questions you may have about the study.
The first screening visit will consist of obtaining participants' informed consent to participate in the study, completing cognitive testing, answering questions about participants' thoughts and feelings, and providing information about participants' medical and psychiatric history.
If participants are deemed eligible at this phase, the investigators will ask participants to come in for an in-person medical screening (up to 2 hours). This in-person medical screen visit will consist of getting your vitals taken (heart rate/blood pressure), undergoing a blood draw, and providing a urine sample. Additionally, people who are or suspect they may become pregnant throughout the course of the study will be given a pregnancy test.
If a participant is deemed eligible after the medical screen, the investigators will ask participants to come in for another in-person visit (2 hours) that would involve a non-invasive brain scan. Participants will then be randomized to receive guanfacine plus sertraline or placebo plus sertraline for an 8 week treatment phase.
Starting week 1 and for every week during the 8-week treatment phase, participants will complete nightly medication log surveys, passive sampling with the BiAffect application, and conduct cognitive testing. Additionally, starting week 1 and every week thereafter, participants will attend a virtual physician visit. At the end of week 8, the investigators will conduct an MRI visit that resembles the initial MRI visit. Participants will be unblinded over weeks 9-10 to arrange for the participants' transition out of the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participants in C+ and C- subgroups will be randomized to one of two treatment arms
| Arm | Type | Receives |
|---|---|---|
| Sertraline + Guanfacine | Experimental | Drug: GuanfacineWe 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. |
| Sertraline + Placebo | Experimental | Drug: SertralineWe 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (35 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GuanfacineGuanfacine immediate release is an established and safe FDA-approved treatment that acts directly by stimulating α2A adrenoceptors. | Drug | Sertraline + Guanfacine |
| SertralineSertraline is a well-tolerated FDA-approved antidepressant that is among the most widely prescribed medications for depression. | Drug | Sertraline + Placebo |
Primary outcome
Remission of depressive symptoms
Time frame: 8 weeks
A score of <=5 on the PHQ-9
2 secondary outcomes
Change in disability
Time frame: 8 weeks
Change in quality of Life
Time frame: 8 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Leanne Williams, PhD principal investigator
Stanford University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Guanfacine and Sertraline in people with Depression, run by Stanford University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Leyla Boyar, BA (6504989326, ljboyar@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Remission of depressive symptoms (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.