CARED : A Novel Rapid Treatment Paradigm for Depression

Official title

The Carolina Recovery From Depression Protocol (CARED) : A Novel Rapid Treatment Paradigm for Depression

Overview

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).

Detailed description

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 interventions for Major Depressive Disorder. In this trial, participants will receive 3 interventions in a single session: psychotherapy, Intermittent Theta Burst Stimulation (iTBS), and participants will be randomized to receive either active or placebo Transcranial Alternating Current Stimulation (tACS). Additionally, Clinical assessments of depression symptoms are performed at Screening (for eligibility), Baseline (at start of day, prior to any intervention), Follow up 1 (FUP1); 2 weeks after SSI) and Follow up 2 (FUP2; 3 months after SSI). Additional assessments of anxiety symptoms, emotion regulation, clinical improvement and quality of life are included.

Primary Objective:

* Establish the safety, feasibility, and tolerability of the SSI

Second Objective:

* Establish the efficacy of the SSI for the treatment of depression symptoms by determining symptom reduction 2 weeks after completion of SSI. * Determine whether the combined effect of psychotherapy, TMS and tACS for treating depression reduces symptoms above and beyond TMS and therapy alone at FUP1. * Determine the longevity of intervention effectiveness (if effective) via follow up (FUP) timepoints for both groups and between groups by comparing scores at FUP1 to scores at FUP2

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 thr
• 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
• 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 pres
• 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.

Primary outcome measures

• Safety via the presence of any serious AEs [Time frame: Day 0 (Baseline) to Day 90 (Follow-up 2)]
• Feasibility of the Single Session Intervention [Time frame: Day 0 (Baseline)]

Secondary outcome measures (2)

• Change in Hamilton Depression Rating Scale-17 (HDRS-17) score following Single Session Intervention. [Time frame: 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. [Time frame: Day 14 (Follow Up 1) to Day 90 (Follow-up 2)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Carolina Center for Neurostimulation — Chapel Hill

Identifiers

NCT: NCT07507370 · 26-0141

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗