Safety and Feasibility of Nasal Delivery of Human Dental Follicle Mesenchymal Stem Cell-Derived Exosomes for Negative Symptoms in Treatment-Resistant Schizophrenia: A Pilot Study

The goal of this clinical trial is to determine the safety and feasibility of nasal delivery of human dental follicle mesenchymal stem cell-derived exosomes in the treatment of negative symptoms of treatment-resistant schizophrenia. It will also learn about the preliminary efficacy of the exosomes. The main questions it aims to answer are:

Is the safety of the exosomes enough for participants? Is the feasibility of nasal delivery of exosomes for participants? Do the exosomes exert any benefits on the negative symptoms of treatment-resistant schizophrenia?

Participants will:

Take a nasal spray of exosomes twice weekly for 2 months Take vital sign checks every day, regular visits for an interview, and lab examinations

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia Negative Type
• Intervention / Treatment: Biological: hDFSCs-Exo

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Zigong Mental Health Center; Phone Number: +86 15881342476; Email: liubo2511@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1) Conforms to the ICD-10 diagnosis of schizophrenia; 2) age between 18 and 60 years old; 3) course of more than 5 years of long-term inpatients; 4) the last 6 months without acute aggravating period, and no change in recent two months regimen; 5) to including clozapine, two different antipsychotics enough poor foot therapy treatment response; 6) positive and negative symptoms scale - negative symptom factor (PANSS - FSNS) 24 or more; 7) three core of PANSS negative symptoms (N1, N4 interchange and N6) at least 2 or 4; 6) clinical overall impression scale - illness severity (-s) CGI score of 4 or more points; 7) signed a written informed consent.

Exclusion Criteria:

1) Has a history of severe allergies; 2) there is a clear brain organic disease; 3) with serious body disease (such as the instability of coronary artery disease, malignant arrhythmia, liver and kidney function is not complete, bronchial asthma, COPD acute aggravating period, autoimmune diseases, etc.); 4) there is accord with the ICD - 10 patients with other psychiatric diagnosis standard sample obstacles (such as schizoaffective disorder, schizophrenia, bipolar I disorder, bipolar type Ⅱ dysfunction, broad developmental disabilities, mental retardation, delirium, dementia, forgotten obstacles or other cognitive impairment, etc.); 5) condition fluctuation, the need to adjust the drug solution; 6) don't cooperate with treatment, 7) with severe rhinitis, nasal allergies; 8) for nearly three months has a history of MECT therapy; 9) suicide risk; 10) during pregnancy or lactation women, female or male subjects and spouse has pregnancy at the time of test plan or over 3 months to test is not willing to use effective contraception (effective contraceptive measures such as birth control pills and condoms or intrauterine device, etc.); 11) other unfavorable into groups.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hDFSCs-Exo	Biological: hDFSCs-Exo; Nasal delivery of exosomes derived from human dental follicle mesenchymal stem cells (1×10^9, 2×10^9, 4×10^9, 8×10^9, 16×10^9) twice weekly for eight weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence and severity of adverse events (AE) and serious adverse events (SAE).		week 0, 2, 4, 8, 12, 16, 20, and 24
Incidence of dose-limiting toxicity (DLT)	Specific toxic reactions related to the investigational drug that occur during the DLT observation period (within 28 days after a single administration)	The observation period for DLT is within 28 days after a single administration
The incidence rate of abnormal laboratory tests	Blood routine, liver and kidney function (elevated ALT/AST, elevated creatinine, etc.), myocardial enzyme spectrum, inflammatory factors, allergic indicators (IgE)	Week 0, 2, 4, 8, 12, 16, 20, and 24
The incidence of abnormal vital signs and electrocardiogram (ECG)		Week 0, 2, 4, 8, 12, 16, 20, and 24
Drug administration completion rate		week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in the total score and negative symptom factor score of the PANSS scale	week 0, 4, 8, 12, and 24
Changes in the total score and subscale scores of SANS (Negative Symptom Rating Scale)	week 0, 4, 8, 12, and 24
Changes in the Clinical General Impression Scale - Severity (CGI-S) score	Week 0, 4, 8, 12, 24
Changes in the Calgary Schizophrenia and Depression Scale (CDSS) score	Week 0, 4, 8, 12, 24
Changes in the Montreal Cognitive Assessment Scale (MoCA) score	week 0, 4, 8, 12, 24
Changes in the completion time of connection test A/B (TMT-A/B)	week 0, 4, 8, 12, 24
Score changes of the Digit Span Test	week 0, 4, 8, 12, 24
Changes in Language Learning and Memory Test (VLMT) scores	week 0, 4, 8, 12, 24

Other Outcome Measures

Outcome Measure	Time Frame
Changes in the functional connections of brain networks in MRI	week 0, 8
The change in the concentration of oxygenated hemoglobin (Oxy-Hb) in fNIRS	week 0, 8

Collaborators and Investigators

• Sponsor: Zigong Mental Health Center
• Collaborators: Chengdu Celincare Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 16, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 20260101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No