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

Overview

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.

Interventions

• Drug fecal microbiota transplantation
  Take fecal microbiota capsules.
• Drug Placebo
  Take placebo capsules.

Primary outcome measures

• 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. [Time frame: from baseline to week 24]
• Cognition: Comparison of the average change in Auditory Verbal Learning Test between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• 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. [Time frame: from baseline to week 24]
• Cognition: Comparison of the average change in Verbal Fluency Test between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• Cognition: Comparison of the average change in Boston Naming Test between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• Cognition: Comparison of the average change in Stroop Color- Word Association Test between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• Cognition: Comparison of the average change in Symbol Digit Modalities Test between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• Cognition: Comparison of the average change in Clock drawing test between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• Cognition: Comparison of the average change in MOCA between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• Cognition: Comparison of the average change in Subjective Cognitive Decline 9 between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]

Secondary outcome measures (12)

• Safety: Proportion of participants with treatment-related adverse events, serious adverse events, or adverse events of special interest. [Time frame: from baseline to week 24]
• macrovascular complications：Comparison of the average change in Carotid Intima-Media Thickness between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• macrovascular complications：Comparison of the average change in Arterial Pulse Wave Velocity between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• macrovascular complications：Comparison of the average change in Ankle-Brachial Index between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• microvascular complications：Comparison of the average change in Albumin-to-Creatinine Ratio between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• microvascular complications：Comparison of the average change in Estimated Glomerular Filtration Rate between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• 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. [Time frame: from baseline to week 24]
• 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. [Time frame: from baseline to week 24]
• Glycemic control：Comparison of the average change in Hemoglobin A1c between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• Glycemic control：Comparison of the average change in Time in Range between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• Glycemic control：Comparison of the average change in Time Above Range between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]
• Glycemic control：Comparison of the average change in Time Below Range between the experimental and control groups from baseline to week 24. [Time frame: from baseline to week 24]

Eligibility criteria

Inclusion criteria

• 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.
• Age between 18 and 60 years, with a diabetes duration of 10 years or more
• Glycated hemoglobin levels ranging from 6.5% to 9.0%.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South Universi — Changsha

Identifiers

NCT: NCT06496412 · T1D cognitive impairment FMT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗