CARED : A Novel Rapid Treatment Paradigm for Depression

Summary

The purpose of this study is to primarily assess the feasibility and secondarily assess the efficacy of a single session intervention (SSI) that combines non-invasive brain stimulation and psychotherapy for Major Depressive Disorder (MDD). investigators will recruit 30 people with MDD, with at least mild to moderate symptoms, who are resistant to typical treatments for Major Depressive Disorder. In this trial, participants will receive psychotherapy, Intermittent Theta Burst Stimulation Transcranial Magnetic Stimulation (iTBS), and either active or sham (placebo) Transcranial Alternating Current Stimulation (tACS).

Conditions

• Major Depressive Disorder

Interventions

DEVICE

Intermittent Theta Burst Stimulation (iTBS)

The TMS stimulation will be delivered using the MagPro X100 system (MagVenture Inc., Alpharetta, Georgia, USA). Participants will receive theta-burst stimulation (iTBS) consisting of 1,800 biphasic pulses delivered in bursts of three pulses at 50 Hz, repeated at 5 Hz (2-s trains, 8-s inter-train interval, 30 trains total per block), at an intensity of 90 % of the resting motor threshold. TMS will be delivered before each tACS/therapy block (over the tACS electrodes), totaling 5 blocks of TMS throughout the single session intervention.

DEVICE

Transcranial Alternating Current Stimulation (tACS)

The alpha and -theta tACS stimulation will be delivered using the neuroConn DC Stimulator MC.The interventional tACS stimulation will be 120 minutes of tACS total; 60 minutes will be delivered during the second block of therapy and 60 minutes will be delivered during the third block of therapy.F3 and F4 will be stimulated 'in-phase', with 1 mA applied at each location, and Cz will be stimulated 'anti-phase' with 2mA applied (zero to peak). tACS will be delivered with a 20 second ramp up and ramp down, at the beginning and end of stimulation. The stimulation amplitude delivered is standard for tACS studies conducted in the Frohlich Lab.

BEHAVIORAL

Psychotherapy

The three, 1-hour psychotherapy blocks were designed to incorporate effective components from multiple psychotherapies, with an emphasis on functional analysis to define the presenting concern, followed by Behavioral Activation (BA) and Acceptance and Commitment Therapy modules to target low mood and psychological flexibility, respectively. The SSI was designed to incorporate ACT principles throughout the modules, guided by the tenets of psychological flexibility, as described by Hayes. Be present, open up, do what matters. The manual was created by a team of several advanced clinical trainees and two licensed clinical psychologists. The last 10 minutes of each session will be spent briefly reviewing the day's activities, what stood out for participants (negative or positive), and whether they had feedback for the clinician.

DEVICE

Sham (Placebo) Transcranial Alternating Current Stimulation (tACS)

Participants will be fitted with the same tACS setup and will receive sham tACS in which alpha-theta tACS is delivered for 40 seconds before ramping down to close to 0 mA of current (20 second ramp up and ramp down; total 80 seconds of stimulation). This active sham is designed to mimic the sensation of receiving stimulation without delivering a sufficient dose of tACS to influence the efficacy of the SSI.

Sponsors & Collaborators

• Foundation of Hope, North Carolina

  collaborator OTHER

• University of North Carolina, Chapel Hill

  lead OTHER

Principal Investigators

• Flavio Frohlich, PhD · University of North Carolina, Chapel Hill

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-14

Primary Completion

2028-07-01

Completion

2028-07-01

FDA Device

Yes

Countries

• United States

Study Locations