Focused stereotactic X-ray to the subgenual anterior cingulate for treatment‑resistant depression
The Efficacy and Safety of Stereotactic Radiotherapy for Treatment-Resistant Depression: An Open-Label Exploratory Study
This study will try using focused stereotactic X‑ray radiation (ZAP‑X) aimed at the subgenual anterior cingulate cortex to see if it reduces symptoms in adults (18–50) with treatment‑resistant major depression.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 9 (estimated) |
| Ages | 18 Years to 50 Years |
| Sex | All |
| Sponsor | Capital Medical University Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, radiation |
| Locations | 1 site (Beijing) |
| Trial ID | NCT07274917 on ClinicalTrials.gov |
What this trial studies
Participants with recurrent major depressive disorder who failed at least two adequate antidepressant trials and have a HAMD‑17 score ≥20 will receive focused stereotactic radiotherapy (ZAP‑X) targeted to the subgenual anterior cingulate cortex (sgACC). The treatment delivers highly localized radiation beams from multiple angles to modulate the target without surgical implantation. Investigators will monitor depressive symptoms, safety, and brain imaging biomarkers over follow‑up visits to detect clinical response and adverse effects. The approach is positioned as a non‑invasive alternative to invasive neurosurgical interventions for a narrowly defined TRD population.
Who should consider this trial
Good fit: Adults aged 18–50 with recurrent major depressive disorder without psychotic features, documented failure of at least two adequate antidepressant trials in the current episode, and a HAMD‑17 score of 20 or higher are the intended candidates.
Not a fit: People outside the 18–50 age range, those without documented treatment‑resistant depression, or patients with psychotic features or other major contraindications to brain radiation are unlikely to benefit from this intervention.
Why it matters
Potential benefit: If successful, this could offer a non‑invasive option to reduce depressive symptoms for patients who have not improved with multiple antidepressant medications.
How similar studies have performed: This is a novel psychiatric application of stereotactic radiotherapy with small preliminary reports showing metabolic changes in targeted brain regions but limited published evidence of consistent clinical benefit to date.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Outpatients or inpatients aged 18 to 50 years (inclusive), regardless of gender. * Meet the diagnostic criteria for Major Depressive Disorder (MDD), recurrent, without psychotic features, as defined by The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). * Documented treatment-resistant depression, defined as a lack of clinically meaningful response (less than 50% improvement in depressive symptoms) to at least two adequate antidepressant trials during the current episode, as recorded by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ). An adequate trial requires sufficient dosage (within the recommended therapeutic range) and duration (at least 6 weeks). The current episode must involve at least one treatment failure. * A Hamilton Depression Rating Scale 17-item (HAMD-17) total score of ≥ 20 at both the screening and baseline visits. * The subject agrees to maintain their existing baseline antidepressant therapy regimen unchanged throughout the study period. * The patient and their legal guardian understand and voluntarily agree to participate in this study, are capable of adhering to the treatment protocol, and provide written informed consent. Exclusion Criteria: * A current or prior diagnosis of any other DSM-5 mental disorder, including but not limited to: neurodevelopmental disorders, bipolar and related disorders, obsessive-compulsive and related disorders, schizophrenia spectrum and other psychotic disorders, substance-related and addictive disorders, or personality disorders. * A past medical history or current presence of clinically significant somatic diseases, such as severe or unstable cardiovascular, respiratory, digestive, endocrine, urinary, hematological, or nervous system diseases, or benign/malignant tumors; or any condition deemed by the investigator to pose a potential risk to patient safety or their ability to fully participate in the study. * Any severe neurological disease or impairment, including but not limited to: any condition potentially associated with increased intracranial pressure, space-occupying brain lesions, cerebral infarction, intracranial hemorrhage, history of epileptic seizures or family history of epilepsy (except for those induced by ECT), cerebral aneurysm, Parkinson's disease, Huntington's disease, multiple sclerosis, or a history of severe head trauma with loss of consciousness; or any condition deemed by the investigator to pose a potential risk to patient safety or their ability to fully participate in the study. * Assessed by the investigator as being at significant risk of suicide, evidenced by: a "Yes" response to Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) in the "Suicidal Ideation" section of the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past 6 months; OR a "Yes" response to any item in the "Suicidal Behavior" section of the C-SSRS (actual attempt, interrupted attempt, aborted attempt, preparatory acts or behavior) within the past 6 months; OR a score of ≥5 on Item 10 (Suicidal Thoughts) of the Montgomery-Åsberg Depression Rating Scale (MADRS). * Participation in other systematic neuromodulation therapies (e.g., MECT, rTMS, tDCS, VNS, DBS) within 3 months prior to screening, or participation in an interventional clinical trial within 1 month prior to screening. * Patients who have been non-responsive to a systematic course of MECT treatment. * Patients with a history of other psychosurgical procedures (including radiofrequency ablation, focused ultrasound, etc.). * A history of prior radiotherapy, chemotherapy, or immunotherapy, or a history of occupational exposure to radiation/toxic substances. * Contraindications to Magnetic Resonance Imaging (MRI), including but not limited to: intracranial or bodily metallic implants, implanted pacemakers or cochlear implants, or claustrophobia. * Pregnant or lactating women. * Subjects of either gender who plan to become pregnant within the next 6 months or are unwilling to use effective contraception. * Subjects with a body weight exceeding 150 kg. * Any other condition considered by the investigator to make the subject unsuitable for participation in this study.
Where this trial is running
Beijing
- Beijing Anding Hospital, Capital Medical University — Beijing, China (Recruiting)
Study contacts
- Principal investigator: Gang Wang, Medical Doctor — Beijing Anding Hospital, Capital Medical University
- Study coordinator: Aihong Yu, Prof., Medical Doctor
- Email: yuaihong@mail.ccmu.edu.cn
- Phone: +86 13811681390
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.