Clinical trial NCT06979440: Study on the Molecular Mechanism of Berberine to Improve Type 2 Diabetes Mellitus Complicated With Depression
Official title: Study on the Molecular Mechanism of Berberine Regulating the Gut Microbiota-derived Metabolites 5-AVAB to Improve Type 2 Diabetes Mellitus Complicated With Depression.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diabetes-Related Complications
Keywords: Type 2 diabetes mellitus
depression
Diabetes Complications
Lead sponsor: Affiliated Hospital of Nantong University
Sponsor class: OTHER
First posted: 2025-05-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The Con group was diagnosed with type 2 diabetes and had no history of mental disorders such as depression; The T2DD patient group was diagnosed with type 2 diabetes and depression, where the depression met the DSM-5 diagnostic criteria for recurrent depression without psychotic symptoms or single-episode MDD, and the total score of the HAMD-17 scale was ≥22 points;

Brief summary: The incidence of type 2 diabetes with comorbid depression (T2DD) is notably high, characterized by prolonged disease duration and susceptibility to recurrence. The preliminary experiments identified 5-AVAB, a gut microbiota-derived metabolite, as a potential novel biomarker for T2DD progression. Given the absence of existing research in this area, it warrants in-depth investigation.

The investigators plan to collect fecal and serum samples from participants with type 2 diabetes and those with T2DD to quantify 5-AVAB levels, as well as conduct in vitro gut microbiota culturing and sequencing studies.

Detailed description: This study will enroll two groups of participants: a control group (with type 2 diabetes) and a T2DD group (with type 2 diabetes with comorbid depression) (n=20 per group). From each participant, 5 mL of whole blood and 5 g of fresh stool will be collected. The whole blood samples will be processed for serum extraction. The 5-AVAB concentrations in all samples will be quantified using LC-MS/MS and compared between groups.

Anaerobic culture medium will be prepared, and the fresh stool samples will be homogenized with the medium at a ratio of 1 g:20 mL. After 20 minutes of pre-incubation at 37°C under anaerobic conditions, berberine will be added at concentrations of 10 μg/mL, 50 μg/mL, and 100 μg/mL, followed by incubation for 2, 6, 12, and 24 hours. The 5-AVAB levels in each group will then be measured using LC-MS/MS. The additional requirements are as follows:

1. Exit and termination criteria If the subject stops the study before sampling, it will be regarded as exit/termination of the study.
2. The time the participants participated in the study (each time and total time) The time from the start of the group to the completion of sampling is regarded as the time of participation in the study.
3. Recruitment process After review and approval by the Ethics Committee of the Affiliated Hospital of Nantong University, this study can start recruiting. It is planned to recruit in the Department of Endocrinology and Department of Neurology of this hospital, and it is expected to recruit 40 participants without any compensation.

Eligibility criteria: Inclusion Criteria:

1. Aged 18-65 years (including the critical value), regardless of gender;
2. The Con group was diagnosed with type 2 diabetes and had no history of mental disorders such as depression;
3. The T2DD patient group was diagnosed with type 2 diabetes and depression, where depression met the DSM-5 diagnostic criteria for recurrent depression without psychotic symptoms or single-episode MDD, and the total score of the HAMD-17 scale was ≥22 points;
4. The subjects read and fully understood the patient instructions and signed the informed consent form.

Exclusion Criteria:

1. Those who do not meet the inclusion criteria;
2. Those who have not used antibiotics, prebiotics, probiotics, enteral nutrition drugs, etc. within 3 months before diagnosis, and those who do not use antibiotics, prebiotics, probiotics, enteral nutrition drugs, etc. during treatment;
3. Those with progressive serious diseases (such as cancer);
4. Those with severe aphasia, agnosia, and apraxia;
5. Those who have used psychotropic drugs for a long time within 1 month before the study or have received new drug research in the past 3 months;
6. Pregnant or breastfeeding women;
7. Alcoholics or drug addicts;
8. Those with poor mental condition and unable to cooperate;
9. Those who are considered unsuitable for inclusion in the study.

Primary outcomes:
measure: The levels of 5-AVAB
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
Study officials:
affiliation: Affiliated Hospital of Nantong University
name: zhengwei zhang, PhD
role: PRINCIPAL_INVESTIGATOR
References: