Sertraline + Guanfacine for Depression

(ACE-D Trial)

Not yet recruiting at 1 trial location

Overseen By Leyla Boyar, BA

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Psychotropics, Sertraline, CYP3A4 inhibitors

Disqualifiers: Bipolar, Psychosis, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how guanfacine (a medication typically used for high blood pressure and ADHD) works with sertraline to improve brain function and thinking skills in people with depression. Researchers aim to determine if this combination alleviates cognitive issues, such as memory and focus problems, often found in depression. Participants will receive either guanfacine and sertraline or a placebo and sertraline to compare effects. This trial targets individuals diagnosed with depression who experience noticeable thinking difficulties. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial may require you to stop taking your current psychotropic medications if they can be safely tapered off. You must wait at least 5 half-lives (time it takes for the drug's concentration to reduce by half) of the medication before the first scan.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sertraline, a common antidepressant, is usually safe and easy to handle. It often causes fewer side effects, such as sleepiness and dizziness, compared to some other antidepressants. However, these side effects may increase with alcohol consumption.

Guanfacine is considered safe for other uses, such as treating attention and behavior issues, and has been studied in various contexts. Although limited information exists on using sertraline and guanfacine together, each is known to be safe individually. The trial is in its early stages, so safety isn't fully confirmed yet, but it shows enough promise to continue. Participants should consult their doctor about any concerns before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for depression, like SSRIs such as sertraline, work by increasing serotonin levels in the brain. But the combination of sertraline with guanfacine is different because guanfacine targets cognitive control deficits, which are often overlooked in standard depression treatments. Researchers are excited about this combination because guanfacine, typically used for ADHD, may enhance cognitive functions and improve overall treatment outcomes for depression. This novel approach could offer a more comprehensive treatment by addressing both mood and cognitive symptoms of depression.

What evidence suggests that this trial's treatments could be effective for depression?

This trial will compare the effects of sertraline combined with guanfacine to sertraline with a placebo. Research has shown that combining sertraline with guanfacine might aid in treating depression, particularly for those with concentration difficulties. In one study, adding guanfacine improved attention and focus. Guanfacine enhances the brain's ability to manage thinking tasks. Another study suggested this combination could alter brain network function, potentially alleviating depression symptoms. Overall, early results appear promising for individuals facing focus and mood challenges. ^{1 2 6 7 8}

Who Is on the Research Team?

Leanne Williams, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for individuals experiencing symptoms of depression. Specific eligibility criteria are not provided, but typically participants must meet diagnostic criteria for the condition being studied and may need to pass certain health assessments to qualify.

Inclusion Criteria

Written informed consent

Meets criteria for cognitive impairment (<=-.5 standard deviation below healthy norms) or intact cognition (within healthy range) subgroups based on a computerized behavioral tests of cognitive control performance (WebNeuro) relative to healthy norms

Fluent and literate in English

Exclusion Criteria

Suicidal ideations representing imminent risk, defined by a score of ≥ 8 on the MINI Plus, or by clinician judgement

History of a DSM-5 bipolar disorder (I, II, not otherwise specified) or psychosis (current or lifetime) established via the participant's medical record and confirmed using the MINI Plus as necessary

History of DSM-5 alcohol or substance use disorder in the last 6 months established via the participant's medical record and confirmed using the MINI Plus as necessary

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive guanfacine plus sertraline or placebo plus sertraline for 8 weeks

8 weeks

4 visits (in-person), 4 visits (virtual)

Unblinding and Transition

Participants are unblinded and arrangements are made for their transition out of the trial

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Guanfacine

Trial Overview

The study investigates how guanfacine, a psychotropic medication, affects brain network functioning in people with depressive symptoms. It also examines the interaction between this drug's effects on brain function and cognitive impairments associated with depression.

How Is the Trial Designed?

Group I: Sertraline + Placebo Experimental Treatment 1 Intervention

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.

Group II: Sertraline + Guanfacine Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

In a long-term study of 240 children aged 6-17 with ADHD, guanfacine extended release (GXR) was found to be generally safe and effective over a treatment period of up to 2 years, with significant improvements in ADHD symptoms as measured by the ADHD Rating Scale.

The most common side effects included somnolence (30.4%) and headache (26.3%), but these were mostly transient, and serious cardiovascular issues were rare, indicating a favorable safety profile for GXR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD. Biederman, J., Melmed, RD., Patel, A., et al.[2022]

Citalopram, a selective serotonin reuptake inhibitor (SSRI), is considered safe for treating depression in adults, including the elderly and those with mild to moderate kidney and liver issues, based on data from clinical trials and published studies.

Common side effects like nausea and dry mouth are mostly mild and transient, and citalopram does not significantly increase the risk of serious issues such as suicide or heart problems, making it comparable in safety to other SSRIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the safety of citalopram. Nemeroff, CB.[2022]

In a long-term study of 191 adults with ADHD, guanfacine extended-release (GXR) was found to be safe, with most treatment-emergent adverse events (TEAEs) being mild to moderate, and only 19.9% of patients discontinuing due to TEAEs.

Significant improvements in ADHD symptoms, quality of life, and executive functioning were observed after 50 weeks of GXR treatment, indicating its efficacy as a long-term management option for adults with ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of guanfacine extended-release in adults with attention-deficit/hyperactivity disorder: an open-label, long-term, phase 3 extension study. Iwanami, A., Saito, K., Fujiwara, M., et al.[2022]

Sertraline hydrochloride effectively blocks the reuptake of serotonin in the brain, making it a promising treatment for depression and obsessive-compulsive disorder, with a recommended daily dose of 50 to 200 mg.

The medication has a favorable safety profile compared to tricyclic antidepressants, although it can cause gastrointestinal side effects like nausea and diarrhea, similar to those seen with fluoxetine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sertraline: a new specific serotonin reuptake blocker. Guthrie, SK.[2019]

In a 9-week study involving 461 children and adolescents with ADHD, guanfacine extended release (GXR) significantly improved ADHD symptoms when added to a stable dose of psychostimulants, outperforming placebo.

GXR treatment did not introduce new safety concerns, with most adverse events being mild to moderate, and showed only small decreases in blood pressure and pulse, indicating it is a safe adjunctive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. Wilens, TE., Bukstein, O., Brams, M., et al.[2022]

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