Novel and Conventional Interventions for Cognitive and Emotional Flexibility in Patient Trauma
NOCICEPT
2 other identifiers
interventional
75
1 country
1
Brief Summary
This study is testing whether combining a rapid form of transcranial magnetic stimulation (TMS), an oral medication called d-cycloserine (DCS), and therapy can improve brain flexibility and emotional control in adults experiencing moderate-to-severe depression, anxiety, or trauma symptoms. TMS is a non-invasive treatment that uses gentle magnetic pulses to stimulate specific areas of the brain. In this phase of the study, all participants receive active accelerated TMS (delivering multiple brief sessions in a single day) along with DCS, a medication that helps enhance brain learning and plasticity. Participants will be randomly assigned to have TMS directed at one of two brain targets: a region called the precuneus (identified using personalized brain scans) or the dorsolateral prefrontal cortex (a standard area for mood treatment). Afterward, participants are randomly assigned to complete three weeks of either therapist-led talk therapy (a modified Unified Protocol) or self-guided educational videos and readings. The main goals are to determine which brain stimulation target works best and to see whether therapist-led therapy leads to more lasting symptom relief and brain changes compared to self-guided education.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 depression
Started Jun 2025
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2025
CompletedFirst Submitted
Initial submission to the registry
October 5, 2026
CompletedFirst Posted
Study publicly available on registry
October 9, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2027
October 9, 2026
June 1, 2026
1.5 years
October 5, 2026
October 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Patient Health Questionnaire 9 (PHQ-9)
The PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The PHQ-9 test evaluates several factors that revolve around the criteria used to professionally diagnose depression under the current DSM-5. The total score is calculated and can range from zero to 27, with 27 being the highest and indicative of the worst outcome/severity. A score of 20 or higher indicates that severe major depression Scoring between 15 and 19 suggests that there is possibly moderately severe major depression Scoring between 10 and 14 means that you may have a moderate severity depression A score between 5 and 9 reveals that mild symptoms of depression appear to exist
At each study visit, measured at Baseline, and 1-week, 1-month, and 3-months after treatment
Generalized Anxiety Disorder-7 (GAD-7)
The Generalized Anxiety Disorder - 7 Item Scale (GAD-7) is a self-administered questionnaire designed for screening and measuring the severity of generalized anxiety disorder (GAD). The GAD-7 consists of seven items that respondents rate based on their experiences over the past two weeks, with each item scored from 0 (not at all) to 3 (nearly every day). The cumulative score, ranging from 0 to 21, indicates the severity of GAD symptoms, with higher scores corresponding to greater anxiety levels. This simplicity in administration and interpretation makes the GAD-7 a practical tool for healthcare providers to quickly assess anxiety levels and monitor changes over time.
At each study visit, measured at baseline, 1-week, 1-month, and 3 months after treatment
Montgomery-Åsberg Depression Rating Scale (MADRS)
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated interview designed to assess the severity of depressive symptoms and detect change resulting from treatment. It consists of 10 items evaluating core symptoms of depression: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is rated on a 7-point scale ranging from 0 (symptom absent/normal) to 6 (severe/most abnormal). Individual item scores are summed to yield a total score ranging from 0 to 60. Higher total scores reflect greater depression severity (typically classified as 0-6: normal/absent; 7-19: mild; 20-34: moderate; 35-60: severe). Outcome values represent the change in total score from baseline, where negative change values indicate clinical improvement in depressive symptoms.
At each study visit, measured at baseline and 1-week, 1-month, and 3-months after treatment
Study Arms (4)
Precuneus + Unified Protocol
EXPERIMENTALTMS targeted to the precuneus followed by Unified Protocol (therapy) administered by a therapist
Precuneus + Psychoeducation
EXPERIMENTALTMS targeted to the precuneus followed by self-led psychoeducation
DLPFC + Unified Protocol
EXPERIMENTALTMS targeted to the DLPFC followed by Unified Protocol (therapy) administered by a therapist
DLPFC + Psychoeducation
EXPERIMENTALTMS targeted to the DLPFC followed by self-led psychoeducation
Interventions
Single dose of 125 mg of D-cycloserine
TMS delivered to either the DLPFC or the precuneus
Cognitive Behavioral Therapy delivered in an abbreviated schedule by a licensed therapist
Self-lead psychoeducation
Eligibility Criteria
You may qualify if:
- Can safely receive TMS and study drugs
- Stable medication regimen for one month prior to study participation, and for the duration of the study
- Not currently receiving TMS, ECT, or ketamine
- No active safety concerns related to suicidality
- Moderate to severe Major Depressive Disorder as indicated by the Patient Health Questionnaire or Quick Inventory of Depressive Symptomatology
You may not qualify if:
- History of seizures or epilepsy
- History of intracranial pathology or lesions from any etiology
- History of traumatic brain injury including prolonged loss of consciousness more than 15 min
- Signs of increased intracranial pressure
- Any major neurological conditions (ex: recent stroke, tumor, neurodegenerative disorders, etc.)
- Major medical conditions that may cause a medical emergency in case of a - provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
- Severe migraines that may result in treatment intolerance.
- Inability to tolerate MRI.
- Pregnancy
- Known allergy to D-cycloserine
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mclean Hospitallead
Study Sites (1)
McLean Hospital
Belmont, Massachusetts, 02478, United States
Related Publications (2)
Donald A. Vaughn, Brooke Marino, Alex Engelbertson, Aleksandra Dojnov, Lena Johnson, Madison Stine, Fidel Vila-Rodriguez, Nicholas Weiss, Georgine Nanos, Jonathan Downar, Real-world effectiveness of a single-day regimen for transcranial magnetic stimulation using Optimized, Neuroplasticity-Enhanced techniques in Depression (ONE-D): An open-label case series, Transcranial Magnetic Stimulation, Volume 5, 2025, 100200, ISSN 3050-5291, https://doi.org/10.1016/j.transm.2025.100200.
BACKGROUNDRossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.
PMID: 33243615BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Medical Director
Study Record Dates
First Submitted
October 5, 2026
First Posted
October 9, 2026
Study Start
June 1, 2025
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
March 1, 2027
Last Updated
October 9, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will not share