Treatment-Resistant Depression
Conditions
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. The subjects must be at least 18 years old, possess full capacity for civil conduct, be able to fully understand the purpose, process, potential benefits, risks, and adverse reactions of the clinical trial, voluntarily sign a written informed consent form, and agree to strictly abide by all the regulations of the clinical trial protocol, the follow-up plan, and all the inspection requirements. 2. The subjects or their legally authorized representatives (only applicable to those who have partial behavioral limitations due to illness but can clearly express their willingness to participate) may cooperate with the researchers throughout the screening, treatment, regular follow-up, and various clinical evaluations and sample collection work, without any resistance or non cooperation tendency. 3. Meets the DSM-5 criteria for depression diagnosis, without psychotic features; and is currently experiencing a depressive episode with a current depressive episode duration of at least 4 weeks at the time of screening; 4. At the screening and baseline stages, the total score of MADRS is 25 and the CGI-S score for the overall clinical impression is 4; 5. Meets the diagnosis of refractory depression: has used = 2 different pharmacological mechanisms of antidepressants, and after completing an adequate treatment course at the recommended dosage, has not achieved sufficient efficacy (the reduction rate of the Hamilton Depression Scale is < 50%). 6. Agrees to take effective contraceptive measures throughout the study period and within 3 months after the last administration of the trial drug; 7. Currently has no organic mental disorder or secondary depression caused by psychoactive substances/non-addictive substances; 8. Currently or previously has no any type of mania, bipolar disorder, schizophrenia, affective disintegrative mental disorder or other mental disorders and refractory depression; 9. In the past 2 years, has no diagnosis of panic disorder, with or without agoraphobia, obsessive-compulsive disorder, bulimia or anorexia nervosa, post-traumatic stress disorder; 10. During the current depressive episode, has not been hospitalized in a psychiatric hospital; 11. At the screening and baseline stages, the Columbia Suicide Scale (C-SSRS) is at level 3 or below, and there is no clinically significant risk of suicide or self-harm or harming others; 12. Has no history of epileptic seizures or conditions that increase the risk of epileptic seizures; 13. Vision and hearing are sufficient to meet the test requirements; 14. The informed consent form must be signed by a fully competent subject; 15. Can follow the requirements of this study, including relevant clinical examinations, etc.; 16. For patients with refractory depression, through peripheral blood ELISA detection at the baseline, the plasma levels of NRF2 and/or HO-1 are lower than those of the previous TRD patients at baseline in this center.
Exclusion criteria
Exclusion criteria: 1. There are cognitive impairments caused by conditions such as frontotemporal degeneration, vascular dementia (excluding mild vascular cognitive impairment related to risk factors), normal pressure hydrocephalus, and other diseases (such as brain trauma or surgery, infection, immunity, tumor, poisoning and metabolic disorders, etc.); 2. There is severe dysfunction of important organs (such as the heart, lungs, liver, kidneys, etc.): such as severe cardiovascular diseases (hospitalization due to myocardial infarction within 3 months or heart surgery, congestive heart failure or myocardial infarction, severe unstable arrhythmia) (1) Abnormal or hypertrophic cardiomyopathy, severe aortic stenosis, aneurysm, etc.), severe pulmonary diseases (severe pneumonia, respiratory failure, etc.), liver dysfunction (transaminase levels exceeding the upper limit of normal by more than 3 times), renal dysfunction (creatinine and urea nitrogen levels exceeding the upper limit of normal by more than 1.5 times), total bilirubin and/or direct bilirubin > 1.5 mg/dL, hemoglobin < 9 mg/dL, positive serological tests for HBV or HCV; absolute neutrophil count < 1,500 cells/mm3 and platelet count < 100,000/mm3, etc., as determined by the investigator to be unsuitable for participating in this clinical trial; 3. Existing or previously diagnosed with Parkinson's disease or mental disorders, such as schizophrenia, bipolar affective disorder, affective disintegrative mental disorder or other mental disorders; 4. CT or MRI evidence of hydrocephalus, stroke, space-occupying lesion, brain infection or any other clinically significant central nervous system disease; 5. Patients with hematological malignancies or solid tumors who are undergoing treatment, have completed treatment within the past 6 months or have evidence of active disease; 6. Current drug or alcohol dependence, including nicotine addiction (smokers); 7. Subjects with acute sinusitis, acute rhinitis, or chronic sinusitis with acute attack symptoms; 8. Abnormalities in the nasal cavity such as nasal granuloma, nasal septum deviation, nasal polyps, etc., judged by the clinical doctor to potentially affect drug administration; 9. Received any nasal drug treatment or nasal surgery treatment before the treatment; 10. Controlled or poorly managed hypertension; 11. Clinical significance of systemic diseases or severe infections within 30 days before screening or during screening; 12. Participants who were involved in other clinical trials within 3 months before the trial enrollment or are currently participating in other clinical trials, and have a history of any type of gene transfer product; 13. Any drugs used by the investigator that may cause cognitive impairment, increase the risk of adverse events (AE) for the participants, or impair the participants' ability to perform cognitive tests or complete the research procedures; 14. Exclusions for the study procedures. 15. Excluding those with a score of grade 3 or above on the Columbia Suicide Scale (C-SSRS) at screening and baseline, or having a clinically significant risk of suicide or self-harm or harming others.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety;Montgomery-?sberg Depression Rating Scale, MADRS;Toxicity indicators; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pittsburgh Sleep Quality Index, PSQI;Generalized Anxiety Disorder 7-item scale, GAD-7; | — |
Countries
China
Contacts
Public ContactXiangdong Tang/ Xiawei Wei
West China Hospital, Sichuan University
Outcome results
None listed