Stereotactic Radiotherapy Treatment for Treatment-resistant Depression

NCT07274917 | Recruiting FDA Device

• 1 other identifier: 2025(60)
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an clinical trial aimed at evaluating the effectiveness and safety of stereotactic radiotherapy for treatment-resistant depression

Conditions

Treatment-Resistant Depression; Depressive Disorder

Keywords

Treatment-Resistant depression; X-ray; subgenual anterior cingulate cortex; ZAP-X; stereotactic radiotherapy

Outcome Measures

Primary Outcomes (1)

• Change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score at 4 weeks post-treatment compared to baseline

  A ten item questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.

  Pre-treatment and 4 weeks post treatment

Secondary Outcomes (10)

• Change in the Montgomery Asberg Depression Rating Scale (MADRS)

  Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)

• Change in Columbia Suicide Severity Rating Scale (C-SSRS) score post-treatment

  Pre-treatment to post-treatment(week 1, week2, week4, week8, week12)

• Change in Quick Inventory of Depressive Symptomatology (QIDS-SR-16) score post-treatment

  Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week 8, week12)

• Change in clinical global impression-severity(CGI-S) post-treatment

  Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)

• Change in clinical global impression-improvement(CGI-I) post-treatment

  Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)

Other Outcomes (3)

• Neuroimaging markers at 4/12 week post-treatment compared to baseline

  4/12 week post-treatment

• Magnetoencephalography (MEG) markers at 1/2/4/8/12week post-treatment compared to baseline

  Baseline, 1/2/4/8/12 week post-treatment

• Digital phenotype post-treatment compared to baseline

  Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)

Study Arms (3)

Intervention Group: 15Gy

EXPERIMENTAL

All patients will then undergo 3 (minimum)-7 (maximum) MRI scans during baseline preparation period, with intervals of more than 24 hours between scans. Based on the axial enhanced 3D T1-weighted MRI image, the anterior commissure (AC) and posterior commissure (PC) are determined. Select the sagittal T1 image and identify the cingulate sulcus below the genu of the corpus callosum. Draw a line from the genu of the corpus callosum to the anterior commissure and take the midpoint. Then, on the coronal T1 image, locate the coronal section corresponding to this midpoint as the target point. The target point will be adjusted manually to avoid overlapping with brain blood vessels, The treatment schedule was as follows: each patient received unilateral irradiation per day at a dose of 15 Gy, with each session lasting approximately 20 minutes. The entire treatment was completed over two days, and the isodose lines were set at 80%

Device: ZAP-X

Intervention Group: 20Gy

EXPERIMENTAL

All patients will then undergo 3 (minimum)-7 (maximum) MRI scans during baseline preparation period, with intervals of more than 24 hours between scans. Based on the axial enhanced 3D T1-weighted MRI image, the anterior commissure (AC) and posterior commissure (PC) are determined. Select the sagittal T1 image and identify the cingulate sulcus below the genu of the corpus callosum. Draw a line from the genu of the corpus callosum to the anterior commissure and take the midpoint. Then, on the coronal T1 image, locate the coronal section corresponding to this midpoint as the target point. The target point will be adjusted manually to avoid overlapping with brain blood vessels, The treatment schedule was as follows: each patient received unilateral irradiation per day at a dose of 20 Gy, with each session lasting approximately 20 minutes. The entire treatment was completed over two days, and the isodose lines were set at 80%

Device: ZAP-X

Intervention Group: 25 Gy

EXPERIMENTAL

All patients will then undergo 3 (minimum)-7 (maximum) MRI scans during baseline preparation period, with intervals of more than 24 hours between scans. Based on the axial enhanced 3D T1-weighted MRI image, the anterior commissure (AC) and posterior commissure (PC) are determined. Select the sagittal T1 image and identify the cingulate sulcus below the genu of the corpus callosum. Draw a line from the genu of the corpus callosum to the anterior commissure and take the midpoint. Then, on the coronal T1 image, locate the coronal section corresponding to this midpoint as the target point. The target point will be adjusted manually to avoid overlapping with brain blood vessels, The treatment schedule was as follows: each patient received unilateral irradiation per day at a dose of 25 Gy, with each session lasting approximately 20 minutes. The entire treatment was completed over two days, and the isodose lines were set at 80%

Device: ZAP-X

Interventions

ZAP-X DEVICE

The individualized bilateral sgACC template will be imported into the ZAP-X treatment planning system. For left and right sgACC targets, the treatment plan will be automatically generated with the following set-up. The treatment will be carried out on two consecutive days.

Intervention Group: 15Gy; Intervention Group: 20Gy; Intervention Group: 25 Gy

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Capital Medical University: lead
• Chinese PLA General Hospital: collaborator

Study Sites (1)

Beijing Anding Hospital, Capital Medical University

Beijing, China

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Study Officials

• Gang Wang, Medical Doctor

  Beijing Anding Hospital, Capital Medical University

  PRINCIPAL INVESTIGATOR

• Longsheng Pan, Medical Doctor

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aihong Yu, Prof., Medical Doctor

CONTACT

+86 13811681390; yuaihong@mail.ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dean of Beijing Anding Hospital

Study Record Dates

• First Submitted: November 28, 2025
• First Posted: December 10, 2025
• Study Start: January 26, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

CN (1)