Treatment-Resistant Depression
Conditions
Interventions
if more than one subject in this group experienced DLT, the trial would be terminated
if no DLT occurred, the dose could be increased to the next level. If two subjects in a certain dose group experienced DLT, the trial would be terminated, and the previous dose level's stimulus amount
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 aged 18 years or above, 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 the relevant examination requirements. 2. The subjects or their legal authorized representatives (applicable only to those with partial behavioral limitations due to illness but who can clearly express their willingness to participate) can fully cooperate with the researchers to complete the screening, treatment, regular follow-up, and all clinical evaluations, sample collection work throughout the entire process, without resistance or non-cooperation tendencies. 3. They must meet the DSM-5 criteria for depression diagnosis and not have psychotic features; and at the time of screening, they must be in a depressive episode and the current duration of the depressive episode must have lasted for at least 4 weeks. 4. At the screening and baseline, the total score of MADRS is 25 points and the CGI-S score of the clinical global impression scale is 4 points. 5. They meet the criteria for treatment-resistant depression: have used >= 2 different pharmacological mechanisms of antidepressants, completed sufficient treatment courses at the recommended doses, and have not achieved sufficient efficacy (the reduction rate of the Hamilton Depression Scale is < 50%). 6. Agree to take effective contraceptive measures throughout the entire study period and within 3 months after the last administration of the trial drug. 7. Currently, there is no organic mental disorder or secondary depression caused by mental active substances/non-addictive substances. 8. Currently or previously, there is no diagnosis of any type of mania, bipolar disorder, schizophrenia, affective disordered mental disorder, or treatment-resistant depression. 9. In the past 2 years, there is no diagnosis of panic disorder, accompanied or not by agoraphobia, obsessive-compulsive disorder, bulimia or anorexia nervosa, or post-traumatic stress disorder. 10. During the current depressive episode, they have not been hospitalized in a psychiatric hospital. 11. At the screening and baseline, the C-SSRS score is 3 or below and there is no clinically significant risk of suicide or self-harm or harm to others. 12. There is no history of epileptic seizures or conditions that increase the risk of epileptic seizures. 13. Vision and hearing must be sufficient to meet the test requirements. 14. The informed consent form must be signed by a subject with full civil capacity. 15. They can follow the requirements of this study, including relevant clinical examinations, etc. 16. For patients with treatment-resistant depression, through peripheral blood ELISA testing outside the baseline, the plasma TGF-ß1 level is lower than the baseline mean value of previous TRD patients in this center minus 1.0 SD (Mean - 1.0 SD), to enrich the TGF-ß1 low-expression subtype.
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. Serious dysfunction of vital organs (heart, lung, liver, kidney, etc.) : Severe cardiovascular disease (hospitalization or cardiac surgery due to myocardial infarction within 3 months, congestive heart failure or myocardial infarction, severe unstable arrhythmia, hypertrophic cardiomyopathy, severe aortic stenosis, aneurysm, etc.), severe pulmonary disease (severe pneumonia, respiratory failure, etc.), and hepatic insufficiency (transaminases exceeding the upper limit of the normal range).3 Times or more), renal insufficiency (creatinine and urea nitrogen more than 1.5 times the upper limit of normal), total bilirubin and/or direct bilirubin > 1.5 mg/dL, hemoglobin < 9mg/dL, HBV or HCV seropositive; An absolute neutrophil count of less than 1500 cells per cubic millimeter and a platelet count of less than 100,000 per cubic millimeter were deemed by the investigator to be ineligible for participation in the 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. Cerebral hydrocephalus, stroke, space-occupying lesions, brain infection or any other clinically significant central nervous system diseases with CT or MRI evidence; 5. Patients with hematological malignancies or solid tumors who are undergoing treatment, have completed treatment within the past 6 months or still 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 granulomas, 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. During the screening or within 30 days before or during the screening, there were clinically significant systemic diseases or severe infections; 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. Using any drugs that the investigator believes may cause cognitive impairment, expose the participant to a higher risk of adverse events (AE), or impair the participant's ability to perform cognitive tests or complete the research procedures; 14. Exclusions for the study procedures; 15. Exclusion of screening and baseline C-SSRS level of 3 or above with clinical significant suicide risk or self-harm or harm to others risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy assessment; | — |
Countries
China
Contacts
Public ContactXiangdong Tang
West China Hospital, Sichuan University
Outcome results
None listed