Stereotactic Radiotherapy Treatment for Treatment-resistant Depression

Official title

The Efficacy and Safety of Stereotactic Radiotherapy for Treatment-Resistant Depression: An Open-Label Exploratory Study

Overview

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

Detailed description

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.

Interventions

• 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.

Primary outcome measures

• Change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score at 4 weeks post-treatment compared to baseline [Time frame: Pre-treatment and 4 weeks post treatment]

Secondary outcome measures (10)

• Change in the Montgomery Asberg Depression Rating Scale (MADRS) [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 [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 [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 [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 [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 [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 [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 [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 [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 [Time frame: Pre-treatment to post-treatment(on day 3, week 1, week 2, week 4, week8, week12)]

Eligibility 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.

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

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Anding Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT07274917 · 2025(60)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗