Clinical trial NCT06496412: Safety and Efficacy of Fecal Microbiota Transplantation on Cognitive Function in T1DM
Official title: Safety and Efficacy of Fecal Microbiota Transplantation on Cognitive Function in T1DM: a Randomized Controlled, Triple-blind Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 1 Diabetes
Keywords: type 1 diabetes
fecal microbiota transplantation
cognitive impairment
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2024-07-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a prospective, single-center, parallel-design,1:1 randomized controlled trial with triple blinding. It aims to investigate the effects of fecal microbiota transplantation (FMT) on cognitive function in patients with long-term type 1 diabetes (T1D), as well as its effects on other complications, glycemic control, insulin dosage, insulin resistance, peripheral blood immune cells, serum metabolites, and safety. This study is divided into two phases for recruiting participants. The first phase recruits 10 individuals (experimental group: 5, control group: 5), while the second phase recruits 30 individuals (experimental group: 15, control group: 15).The main research objectives are as follows:

1. To observe the difference in cognitive function between the FMT group and the placebo group, with the indicators including cognitive scale scores, changes in brain MRI imaging indicators and brain age at week 24 compared to baseline.
2. To observe the difference in other complications between the FMT group and the placebo group, with the indicators including changes in urinary albumin/creatinine ratio, fundus photography, carotid intima-media thickness, and arterial pulse wave velocity at week 24 compared to baseline.
3. To observe the difference in glycemic control, insulin dosage, insulin resistance, peripheral blood immune cells, gut microbiota, and serum metabolites between the FMT group and the placebo group.
4. To evaluate the safety of FMT.


Eligibility criteria: Inclusion Criteria:

1. According to the definition of type 1 diabetes mellitus (T1DM) by the World Health Organization (WHO), the diagnostic criteria are as follows: (i) clinically diagnosed as T1D by endocrinologists; (ii) insulin dependence from disease onset and diabetic ketoacidosis (DKA)/diabetic ketosis (DK) at diagnosis; (iii) positive for at least one of islet autoantibodies for glutamic acid decarboxylase antibody \[GADA\], insulinoma-associated protein 2 antibody \[IA-2A\], and zinc transporter 8 antibody \[ZnT8A\]; or negative for all three islet autoantibodies, but diagnosed before age 30.
2. Age between 18 and 60 years, with a diabetes duration of 10 years or more
3. Glycated hemoglobin levels ranging from 6.5% to 9.0%.

Exclusion Criteria:

1. Use of any hypoglycemic medication other than insulin in the two months prior to randomization.
2. Participation in other clinical trials within the two months prior to randomization.
3. Use of antimicrobial drugs, probiotics, intestinal microbiota regulators, and other drugs with significant impact on gut microbiota within the two months prior to randomization.
4. Gastrointestinal diseases: celiac disease, irritable bowel syndrome, Crohn's disease, etc.
5. Severe infections, severe heart, liver, kidney diseases, tumors, and other inflammatory or autoimmune diseases.
6. Pregnant or lactating women, or women planning pregnancy during the study period.
7. Severe mental health disorders such as schizophrenia, major depression, bipolar disorder, alcohol or substance abuse, etc.
8. Neurological disorders such as Parkinson's disease, progressive supranuclear palsy, epilepsy, multiple sclerosis, traumatic brain injury, stroke, etc.
9. Post-implantation of metal materials or contraindications for other MRI examinations.
10. Severe episodes of unconscious hypoglycemia within the past two months.

Primary outcomes:
measure: Cognition:Comparison of the average change in Z-scores for memory and executive domain-related assessments between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in Auditory Verbal Learning Test between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in Trail Making Test Part A and Part B between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in Verbal Fluency Test between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in Boston Naming Test between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in Stroop Color- Word Association Test between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in Symbol Digit Modalities Test between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in Clock drawing test between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in MOCA between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in Subjective Cognitive Decline 9 between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Cognition: Comparison of the average change in Brain MRI between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
Secondary outcomes:
measure: Safety: Proportion of participants with treatment-related adverse events, serious adverse events, or adverse events of special interest.
timeFrame: from baseline to week 24
measure: macrovascular complications：Comparison of the average change in Carotid Intima-Media Thickness between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: macrovascular complications：Comparison of the average change in Arterial Pulse Wave Velocity between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: macrovascular complications：Comparison of the average change in Ankle-Brachial Index between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: microvascular complications：Comparison of the average change in Albumin-to-Creatinine Ratio between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: microvascular complications：Comparison of the average change in Estimated Glomerular Filtration Rate between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: microvascular complications：Compare the differences in the proportion of abnormal fundus photography and the severity of progression between the experimental and control groups during the follow-up period.
timeFrame: from baseline to week 24
measure: microvascular complications：Comparison of the average change in Neuropathy lmpairment Score in the Lower Limbs between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Glycemic control：Comparison of the average change in Hemoglobin A1c between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Glycemic control：Comparison of the average change in Time in Range between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Glycemic control：Comparison of the average change in Time Above Range between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Glycemic control：Comparison of the average change in Time Below Range between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Glycemic control：Comparison of the average change in Glucose Management Indicato between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Glycemic control：Comparison of the average change in Glycemia risk index between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Glycemic control：Comparison of the average change in Coefficient of Variation between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Glycemic control：Comparison of the average change in Mean Amplitude of Glycemic Excursions between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Blood lipid：Comparison of the average change in triglycerides between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Blood lipid：Comparison of the average change in total cholesterol between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Blood lipid：Comparison of the average change in high-density lipoprotein cholesterol between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Blood lipid：Comparison of the average change in low-density lipoprotein cholesterol between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Blood pressure：Comparison of the average change in blood pressure between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Body Mass Index：Comparison of the average change in body mass index between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Insulin resistance: Comparison of the average change in estimated Glucose Disposal Rate between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Insulin dose: Comparison of the average change in insulin dose between the experimental and control groups from baseline to week 24.
timeFrame: from baseline to week 24
measure: Change in gut composition: Engraftment of fecal microbial transplant as assessed by 16S rRNA sequencing of recipient stool sample
timeFrame: from baseline to week 24
measure: Changes in peripheral blood mononuclear cells: Assessing the effects of fecal microbial transplant on peripheral blood mononuclear cells by flow cytometry.
timeFrame: from baseline to week 24
measure: Changes in peripheral blood metabolites: Assessing the impact of fecal microbiota transplantation on peripheral blood metabolites using metabolomics.
timeFrame: from baseline to week 24
Other outcomes:
Locations:
city: Changsha
country: China
facility: Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
state: Hunan
Study officials:
affiliation: The Second Xiangya Hospital, Central South University
name: Xia Li, MD/PHD
role: PRINCIPAL_INVESTIGATOR
References: