CARED : A Novel Rapid Treatment Paradigm for Depression
CARED
The Carolina Recovery From Depression Protocol (CARED) : A Novel Rapid Treatment Paradigm for Depression
1 other identifier
interventional
30
1 country
1
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable major-depressive-disorder
Started Apr 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 27, 2026
CompletedFirst Posted
Study publicly available on registry
April 2, 2026
CompletedStudy Start
First participant enrolled
April 14, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2028
May 8, 2026
March 1, 2026
2.2 years
March 27, 2026
May 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Safety via the presence of any serious AEs
The number of serious adverse events (SAEs) determined to be related to intervention in both experimental and sham arms.
Day 0 (Baseline) to Day 90 (Follow-up 2)
Feasibility of the Single Session Intervention
Number of enrolled participants who successfully complete the intervention session.
Day 0 (Baseline)
Secondary Outcomes (2)
Change in Hamilton Depression Rating Scale-17 (HDRS-17) score following Single Session Intervention.
Day 1 (Baseline) to Day 14 (Follow-up 1)
Duration of change in Hamilton Depression Rating Scale-17 (HDRS-17) score following Single Session Intervention.
Day 14 (Follow Up 1) to Day 90 (Follow-up 2)
Study Arms (2)
Inactive Sham (Placebo)
ACTIVE COMPARATORParticipants will receive psychotherapy, active iTBS, and sham tACS in which alpha-theta tACS is delivered for 40 seconds before ramping down to close to 0 mA of current. The sham is designed to mimic the sensation of receiving Alpha and Theta tACS without delivering a sufficient dose.
Active tACS: Experimental Arm
EXPERIMENTALParticipants will receive psychotherapy, active iTBS, and active tACS in which alpha-theta tACS will be delivered with a 20 second ramp up and ramp down, at the beginning and end of stimulation followed by 2 mA between the stimulation sites. The stimulation amplitude delivered is standard for tACS studies conducted in the Frohlich Lab
Interventions
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- Any gender, aged 18 - 70
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- DSM-5 diagnosis of unipolar, non-psychotic MDD as evidenced by the Diagnostic Interview for Anxiety, Mood, and Obsessive-Compulsive and Related Neuropsychiatric Disorders (DIAMOND)
- HDRS-17 score ≥14
- Low suicide risk (defined for this study as no active suicidal ideation in the past month and no suicide attempts, preparatory actions, or significant non-suicidal self-harm in the previous 2 years). Risk will be assessed utilizing the Columbia-Suicide Severity Rating Scale (C-SSRS) screen and triage version with further exploration of positive responses.
- Capacity to understand all relevant risks and potential benefits of the study (informed consent).
- For people of childbearing potential: use of highly effective contraception as determined by the Investigator for at least 1 month prior to screening and agreement to use such a method during study participation
- History of treatment resistance as indicated by previously or currently not achieving clinically significant symptom reduction on at least one antidepressant medication. This will be evaluated using the Maudsley Treatment Inventory (MTI). Participants with scores greater than or equal to 3 on the MTI will be included.
You may not qualify if:
- DSM-5 diagnosis of severe alcohol use disorder (AUD) within the last 12 months, as evidenced by the DIAMOND
- DSM-5 diagnosis of moderate to severe substance use disorder (excluding tobacco) within the last 12 months, as evidenced by the DIAMOND
- Lifetime history of bipolar disorder, as evidenced by DIAMOND
- Schizophrenia spectrum and other psychotic disorders, as evidenced by DIAMOND
- History of autism spectrum disorder (self-reported by participants)
- Initiated any new psychotropic medication in the 6 weeks prior to screening or had a dose change in the preceding 6 weeks
- Initiated a new course of psychotherapy in the 6 weeks preceding screening
- Received any neurostimulation treatment in the 6 weeks preceding screening
- History of seizures (excluding febrile seizures in childhood or Electroconvulsive Therapy (ECT) induced seizures)
- Neurological disorders that would increase risk of participation or present a significant confounder in the opinion of the investigator (for example, dementia, history of stroke, Parkinson's disease, multiple sclerosis, history of traumatic brain injury with prolonged loss of consciousness, ruptured cerebral aneurysm, previous CNS radiation)
- Previously failed to respond to ECT or transcranial magnetic stimulation (TMS)
- Prior brain surgery and/or brain implants
- Personal or familia history of epilepsy
- Previous fainting spells or syncope
- Metal in the brain, skull or elsewhere in the body
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Carolina Center for Neurostimulation
Chapel Hill, North Carolina, 27516, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Flavio Frohlich, PhD
University of North Carolina, Chapel Hill
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Participants, research staff, and outcome assessors will all be blind to participant allocation.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 27, 2026
First Posted
April 2, 2026
Study Start
April 14, 2026
Primary Completion (Estimated)
July 1, 2028
Study Completion (Estimated)
July 1, 2028
Last Updated
May 8, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share
Individual participant data will not be shared in this study due to the small sample size, which may cause participants to become identifiable