Cognitive Enhancement in Recurrent Depression (The COG-D-R Study)

NCT07527273 | Not Yet Recruiting FDA Device

• 1 other identifier: 251809
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if a combination of non-drug treatments works to benefit memory, thinking, and brain functioning in older individuals with recurrent depression. The non-drug approaches the investigators are studying include transcranial direct current stimulation (tDCS) and computerized cognitive training. tDCS uses small currents of electricity on the forehead to potentially stimulate your brain's ability to process and learn. Computerized cognitive training uses tablet games to improve memory and thinking. In this study, two different cognitive training programs are being investigated, both of which are stimulating and designed to engage brain activity. One that is believed to be a specific treatment for depression, while the other provides extra stimulation for the brain that is non-specific. Two different tDCS parameters - active stimulation and sham (or placebo) stimulation - are also being investigated. Participants will be randomized to one of three study groups:

• Does "depression cognitive training treatment with active brain stimulation" benefit thinking and memory more so than the other treatments?
• Does "depression cognitive training treatment with active brain stimulation" benefit brain functioning more so than the other treatments? Participants will:
• Complete several baseline and post-intervention visits at the research center for checkups and tests over the course of 3-4 months.
• Visit the research center daily for 4 weeks to complete their assigned treatment.

Conditions

Aging; Depression; Cognitive Symptoms

Keywords

geriatrics; aging; elderly; cognition; memory; thinking; depression; tDCS; cognitive training; cognitive remediation; digital therapeutics

Outcome Measures

Primary Outcomes (2)

• NIH Examiner

  This objective cognitive test battery assesses a range of executive functions (working memory, inhibition, set shifting, fluency, and planning). The investigators will examine intervention-related change its Executive Composite Score (primary outcome), and subcomposite (Cognitive Control, Working Memory, and Fluency; secondary outcomes) scores, where higher scores indicate better performance.

  Baseline, Following completion of the 4-week intervention, 3-month Post-Intervention

• Resting state fMRI functional connectivity

  Functional connectivity from resting state fMRI will be processed using the CONN toolbox for connectivity, incorporating the Shaeffer network atlases to improve peer-research supported network usage in addition to the standard CONN atlases. A priori ROI-to-ROI analyses will be used to determine whether average connectivity changes in the Executive Control Network differs by treatment group. Analyses will control for multiple comparisons at false discovery rate (FDR) \< 0.05.

  Baseline, Following completion of the 4-week intervention

Secondary Outcomes (1)

• Montgomery Asberg Depression Rating Scale

  Baseline and weekly thereafter, Following completion of the 4-week intervention, 3-Month Post-Intervention

Study Arms (3)

Depression Cognitive Training + Active Stimulation

EXPERIMENTAL

This arm receives the depression cognitive training combined with active tDCS.

Behavioral: Depression Cognitive Training; Device: tDCS (active stimulation)

Depression Cognitive Training + Sham Stimulation

EXPERIMENTAL

This arm receives the depression cognitive training combined with sham tDCS.

Behavioral: Depression Cognitive Training; Device: tDCS (sham stimulation)

Non-Specific Cognitive Training + Sham Stimulation

EXPERIMENTAL

This arm receives the non-specific cognitive training combined with sham tDCS.

Behavioral: Non-Specific Cognitive Training; Device: tDCS (sham stimulation)

Interventions

tDCS (active stimulation) DEVICE

A Soterix Clinical Trials Direct Current Stimulator will apply 20 minutes of 2.0 milliamps (mA) direct current through two bicarbon rubber electrodes encased in saline soaked 5 cm x 7 cm sponges (8 cc of 0.9% saline solution per sponge) placed over the frontal cortices at F3 and F4 (via 10-20 system).

Depression Cognitive Training + Active Stimulation

tDCS (sham stimulation) DEVICE

Sham stimulation will be performed with the same device and all procedures will be identical except for the duration of stimulation. Participants will receive 30 seconds of 2 mA of direct current stimulation at the beginning of the session. Participants habituate to the sensation of tDCS within 30-60 seconds of stimulation. This procedure provides the same sensation of tDCS without the full duration of stimulation, making it a highly effective sham procedure.

Depression Cognitive Training + Sham Stimulation; Non-Specific Cognitive Training + Sham Stimulation

Depression Cognitive Training BEHAVIORAL

Computerized cognitive training targeting the underlying cerebral networks associated with depression.

Depression Cognitive Training + Active Stimulation; Depression Cognitive Training + Sham Stimulation

Non-Specific Cognitive Training BEHAVIORAL

Computerized cognitive training that provides extra stimulation for the brain that is non-specific.

Non-Specific Cognitive Training + Sham Stimulation

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 60 years
• Evidence of executive dysfunction via SUBJECTIVE COMPLAINTS (At least one subdomain of the Behavior Rating Inventory of Executive Function in Adults (BRIEF-A) at T \> 65, or At least one average score of \> 1.5 on Planning, Organization, or Attention subdomains of the Everyday Cognition Scale (ECog)) or OBJECTIVE PERFORMANCE (At least one demographically adjusted z-score \> -1.0 SD below the mean on a measure of executive functioning (Digits backward, Trails B, or total Verbal Fluency) on the National Alzheimer's Coordinating Center (NACC) Uniform Data Set 3.0).
• DSM-5 diagnosis of a current or past (within last 3 years) depressive episode (e.g., Major Depressive Disorder (MDD), Persistent Depressive Disorder (PDD)) via the using the Structured Clinical Interview for DSM-5 Disorders (SCID-5).
• Presence of 2 or more lifetime depressive episodes to be considered "recurrent."
• Either stable antidepressant regimen for at least 6 weeks or no current antidepressant treatment (no plans to change treatment over course of study).
• Fluent in English

You may not qualify if:

• Other psychiatric conditions via the SCID-5 (including history of bipolar disorder and psychosis, excluding comorbid anxiety disorders)
• Severe depression (MADRS score \> 29)
• Acute suicidality on clinical evaluation by study clinician and via response on MADRS item 10 (score of 4 or more would require further assessment)
• Acute grief (occurring within past month)
• History of alcohol use disorder or substance use disorder of moderate or greater severity in the last 12 months
• Primary neurological disorder (e.g., epilepsy, brain tumor, Parkinson's disease, Alzheimer's disease, dementia diagnosis)
• Montreal Cognitive Assessment (MoCA) \< 23
• Primary amnestic cognitive profile (\>1.5 SD below demographically-adjusted mean on NACC memory measures in context otherwise normal cognitive profile, or per clinician judgement)
• Any physical or intellectual disability affecting ability to complete assessments
• Unstable medical illness needing urgent treatment
• MRI contraindications
• Electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) in last 2 months
• Current involvement in psychotherapy
• Current involvement in other research studies (including but not limited to: neuromodulation \[TMS or tDCS\] or investigational drug studies). Observational studies \[without intervention\] are acceptable.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

MeSH Terms

Conditions

Depression; Neurobehavioral Manifestations

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Central Study Contacts

Sarah Szymkowicz, PhD

CONTACT

615-875-0032; sarah.szymkowicz@vumc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Triple-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 23, 2026
• First Posted: April 14, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

US (1)