CARED: Rapid single-session combination of brain stimulation and therapy for depression

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This interventional trial will recruit 30 adults with DSM-5 unipolar, non-psychotic major depressive disorder and at least mild-to-moderate symptoms who have shown resistance to typical treatments. Participants receive three interventions in one visit: psychotherapy, intermittent theta-burst transcranial magnetic stimulation (iTBS), and randomized active or sham transcranial alternating current stimulation (tACS). The primary goals are to establish safety, feasibility, and tolerability of the single-session intervention, with secondary measurement of symptom change at 2 weeks and durability at 3 months. Clinical assessments (depression, anxiety, emotion regulation, quality of life) occur at screening, baseline, 2-week follow-up, and 3-month follow-up.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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
* Implanted medical device that uses electricity and any implanted devices in other areas of the head or neck, or implants located \< 30cm from the position of the TMS coil
* Current pregnancy or lactation
* Currently enrolled in another clinical trial for depression
* Unstable medical disorder or anything that would place the participant at increased risk or preclude the participant's full compliance with or completion of the study, in the opinion of the Investigator
* Non-English speaking individuals are excluded because the ability to accurately and completely communicate study information, answer questions about the study, and obtain consent in the English language are necessary, and due to resource constraints it is not feasible to engage an interpreter for language services.

Where it's running

• Carolina Center for Neurostimulation
  Chapel Hill, North Carolina, United States Recruiting

Study contacts

• Principal investigator: Flavio Frohlich, PhD — University of North Carolina, Chapel Hill
• Study coordinator: Flavio Frohlich, PhD
• Email: flavio_frohlich@med.unc.edu
• Phone: 919-966-9929

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.