An interventional study of ZAP-X in Treatment-Resistant Depression and Depressive Disorder, sponsored by Capital Medical University. Completed at 1 site in China. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2026-08-10.
Sponsored by Capital Medical University · Not applicable, Interventional, and Treatment
This study is an clinical trial aimed at evaluating the effectiveness and safety of stereotactic radiotherapy for treatment-resistant depression
Treatment-Resistant Depression (TRD) generally refers to patients with depression who have received at least two antidepressants with different mechanisms of action, at adequate doses and for sufficient durations, but have shown poor or no response. TRD is difficult to treat and usually has a poor prognosis, seriously affecting the normal life of patients and their families. One of the imaging manifestations of TRD patients is abnormal functional activity of the subgenual anterior cingulate cortex (sgACC). The direct clinical intervention method for this area is to implant a deep brain stimulator through an invasive approach. However, this intervention method has a low risk-benefit ratio and is poorly accepted by patients.
Radiation is a widely used clinical intervention technique. By focusing rays from multiple angles, it can generate high-energy rays in a local area of the human brain for ablation. This technique is typically used for targeted ablation of tumors and has the advantage of high precision. Recently, breakthrough research has found that radiotherapy can be applied in the field of psychiatry. In experiments with doses of 10Gy and 20Gy, researchers observed an increase in the standard uptake value of the irradiated target area compared to the contralateral brain region in PET images of the subjects, suggesting that radiotherapy can up-regulate glucose metabolism levels without killing neurons at low doses. These clinical studies suggest that stereotactic radiotherapy can safely regulate brain function. Based on this, this project aims to explore the safety, efficacy, and biological mechanisms of low-dose radiotherapy targeting the sgACC in the treatment of TRD.
461 studies on the registry are indexed under Depressive Disorder, Treatment-Resistant; 148 are open to participants now.
This study's enrollment of 9 is below the median of 53 across 388 interventional studies indexed under Depressive Disorder, Treatment-Resistant.
Browse Depressive Disorder, Treatment-Resistant studies →Capital Medical University is the lead sponsor of 283 studies on the registry; 92 are open to participants now.
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Exclusion Criteria:
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
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
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
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.
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.
Time frame: Pre-treatment and 4 weeks post treatment
Change in the Montgomery Asberg Depression Rating Scale (MADRS)
A ten item diagnostic 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.
Time frame: 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
A suicidal ideation rating scale created by researchers at Columbia University. The score was calculated by summing the answers to 5 questions. Score range - 0 to 5. Higher score indicate higher suicidal ideation.
Time frame: Pre-treatment to post-treatment(week 1, week2, week4, week8, week12)
Change in Quick Inventory of Depressive Symptomatology (QIDS-SR-16) score post-treatment
The QIDS-SR16 consists of 16 items, with each item ranging between 0 and 3 points. The total score ranged from 0 to 27 with higher score implicated severe depressive symptoms.
Time frame: 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
The Clinical Global Impression - Severity (CGI-S) is a single-item, clinician-rated scale used to assess the overall severity of a patient's illness. The rating is based on the clinician's total experience with this patient population. It is scored on a 7-point scale, ranging from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients), with higher scores indicating greater illness severity.
Time frame: 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
The Clinical Global Impression - Improvement (CGI-I) is a single-item, clinician-rated scale used to assess how much a patient's illness has improved or worsened since the start of treatment. It is scored on a 7-point scale, ranging from 1 (Very much improved) to 7 (Very much worse), with a score of 4 representing "No change". The rating is based on the clinician's assessment of the patient's overall clinical state.
Time frame: Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)
Change in Instant Mood Scale-12 post-treatment
The Instant Mood Scale-12 (IMS-12) is a brief, 12-item self-report questionnaire designed to rapidly assess the current severity of depression and anxiety symptoms.Each item is rated on a 7-point Likert scale (0="Not at all" to 7="Extremely") based on the patient's feelings at the present moment. Total scores for each subscale range from 0 to 84, with higher scores indicating greater symptom severity.
Time frame: Pre-treatment to immediate during treatment(on day 1, day 2) and post-treatment(on day 3, week 1, week 2, week 4, week8, week12)
Change in Hamilton Anxiety Scale(HAMA) post-treatment
A 14-item, clinician-administered scale designed to assess the severity of a patient's anxiety. Scores range from 0-56, with higher scores reflecting greater anxiety severity.
Time frame: Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)
Change in Digital Span Test score post-treatment
A test of working memory and attention where participants repeat sequences of auditorily presented numbers, both in forward and backward order. The primary outcome is the longest sequence correctly recalled.
Time frame: Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)
Change in Digit Symbol Substitution Test post-treatment
The Digit Symbol Substitution Test (DSST) is a performance-based neuropsychological test that assesses processing speed, sustained attention, and visual-motor coordination. The test presents the participant with a key pairing nine numbers (1-9) with nine unique symbols. The main task requires the participant to fill in blank spaces with the corresponding symbol for a series of randomly ordered numbers as quickly and accurately as possible within 90 seconds. The primary score is the total number of correct symbol substitutions completed within the time allowed.
Time frame: Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)
Change in Perceived Deficits Questionnaire - Depression score post-treatment
The Perceived Deficits Questionnaire - Depression (PDQ-D) is a 20-item self-report scale designed to measure a patient's subjective experience of cognitive dysfunction. It assesses perceived difficulties in four key cognitive domains: attention/concentration (5 items), retrospective memory (5 items), prospective memory (5 items), and planning/organization (5 items). Patients rate the frequency of these cognitive problems over the past week on a 5-point scale from 0 ("Never") to 4 ("Almost always"). A total score is calculated (range 0-80), with higher scores indicating greater perceived cognitive deficits.
Time frame: Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)
Neuroimaging markers at 4/12 week post-treatment compared to baseline
Time frame: 4/12 week post-treatment
Magnetoencephalography (MEG) markers at 1/2/4/8/12week post-treatment compared to baseline
Time frame: Baseline, 1/2/4/8/12 week post-treatment
Digital phenotype post-treatment compared to baseline
Including Audio and video
Time frame: Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)
Plan to share: Undecided
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This study is completed, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Depressive Disorder, Treatment-Resistant→
Capital Medical University