Washed Microbiota Transplantation for Type 1 Diabetes Mellitus

Type 1 Diabetes Clinical Trial

Official title:

Washed Microbiota Transplantation for Type 1 Diabetes Mellitus: a Real World Research

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06256614
• Other study ID #: WMT-RWS-T1DM
• Status: Recruiting
• Start date: March 1, 2024
• Est. completion date: July 2029

Study information

• Verified date: January 2024
• Source: The Second Hospital of Nanjing Medical University
• Contact: Faming Zhang, PhD
• Phone: 086-025-58509883
• Email: fzhang[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a real-world study to explore the safety and the efficacy of washed microbiota transplantation (WMT) for patients with Type 1 Diabetes Mellitus (T1DM).

Description:

At least 20 subjects who meet all the inclusion criteria but do not meet any exclusion criteria will be enrolled in this study. Data of demographic characteristics, blood glucose fluctuation and variability, daily insulin dosage and clinical outcomes will be collected. After treatment, they will enter the follow-up period for safety and efficacy evaluation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 2029
• Est. primary completion date: January 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 100 Years

Eligibility

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to enter the study:

1. At the time of informed consent, male or non-pregnant or non-lactating female.

2. The diagnostic criteria for T1DM are confirmed by previous medical record.

3. The subject or his/her legal representative gives informed consent, fully nderstands the purpose of the study, is able to communicate effectively with the investigator, and comprehends and complies with the requirements set forth in the study.

Exclusion Criteria:

Subjects meeting any of the following exclusion criteria must be excluded from the study:

1. Diagnosed as any type of diabetes other than type 1 diabetes mellitus;

2. Subjects with severe life-threatening complications diabetes (such as ketoacidosis, or acute coronary syndrome, etc.);

3. At the time of screening, the subject or his/her legal representative refuses to take effective contraception within 3 months after the last treatment.

4. According to the judgment of the investigator, the subjects are not suitable to participate in this clinical study, or participation in this clinical study cannot guarantee the rights and interests of the subjects.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Other:
• WMT
Washed microbiota transplantation refers to the infusion of washed microbiota from healthy donor into patients' gastrointestinal tract. Participants will receive three doses of WMT for T1DM.

Locations

Country	Name	City	State
China	Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Second Hospital of Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (18)

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Experts consensus on management of glycemic variability of diabetes mellitus. Chin J Endocrinol Metab. 2017;33(8):633-636.

Frost F, Kacprowski T, Ruhlemann M, Pietzner M, Bang C, Franke A, Nauck M, Volker U, Volzke H, Dorr M, Baumbach J, Sendler M, Schulz C, Mayerle J, Weiss FU, Homuth G, Lerch MM. Long-term instability of the intestinal microbiome is associated with metabolic liver disease, low microbiota diversity, diabetes mellitus and impaired exocrine pancreatic function. Gut. 2021 Mar;70(3):522-530. doi: 10.1136/gutjnl-2020-322753. Epub 2020 Nov 9. — View Citation

Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition)(Part 1). Chinese Journal of Practical Internal Medicine. 2020;41(8):668-695.

Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition)(Part 2). Chinese Journal of Practical Internal Medicine. 2020;41(9):757-784.

Hsu CR, Chen YT, Sheu WH. Glycemic variability and diabetes retinopathy: a missing link. J Diabetes Complications. 2015 Mar;29(2):302-6. doi: 10.1016/j.jdiacomp.2014.11.013. Epub 2014 Dec 3. — View Citation

Jin SM, Kim TH, Oh S, Baek J, Joung JY, Park SM, Cho YY, Sohn SY, Hur KY, Lee MS, Lee MK, Kim JH. Association between the extent of urinary albumin excretion and glycaemic variability indices measured by continuous glucose monitoring. Diabet Med. 2015 Feb;32(2):274-9. doi: 10.1111/dme.12607. Epub 2014 Oct 29. — View Citation

Li Y, Teng D, Shi X, Qin G, Qin Y, Quan H, Shi B, Sun H, Ba J, Chen B, Du J, He L, Lai X, Li Y, Chi H, Liao E, Liu C, Liu L, Tang X, Tong N, Wang G, Zhang JA, Wang Y, Xue Y, Yan L, Yang J, Yang L, Yao Y, Ye Z, Zhang Q, Zhang L, Zhu J, Zhu M, Ning G, Mu Y, Zhao J, Teng W, Shan Z. Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. BMJ. 2020 Apr 28;369:m997. doi: 10.1136/bmj.m997. — View Citation

Liu J, Liu M, Chai Z, Li C, Wang Y, Shen M, Zhuang G, Zhang L. Projected rapid growth in diabetes disease burden and economic burden in China: a spatio-temporal study from 2020 to 2030. Lancet Reg Health West Pac. 2023 Feb 3;33:100700. doi: 10.1016/j.lanwpc.2023.100700. eCollection 2023 Apr. — View Citation

Lu G, Wang W, Li P, Wen Q, Cui B, Zhang F. Washed preparation of faecal microbiota changes the transplantation related safety, quantitative method and delivery. Microb Biotechnol. 2022 Sep;15(9):2439-2449. doi: 10.1111/1751-7915.14074. Epub 2022 May 16. — View Citation

Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. 2016 Dec 1;167(6):1469-1480.e12. doi: 10.1016/j.cell.2016.11.018. — View Citation

Su G, Mi S, Tao H, Li Z, Yang H, Zheng H, Zhou Y, Ma C. Association of glycemic variability and the presence and severity of coronary artery disease in patients with type 2 diabetes. Cardiovasc Diabetol. 2011 Feb 25;10:19. doi: 10.1186/1475-2840-10-19. — View Citation

Su G, Mi SH, Tao H, Li Z, Yang HX, Zheng H, Zhou Y, Tian L. Impact of admission glycemic variability, glucose, and glycosylated hemoglobin on major adverse cardiac events after acute myocardial infarction. Diabetes Care. 2013 Apr;36(4):1026-32. doi: 10.2337/dc12-0925. Epub 2013 Jan 24. — View Citation

Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013 Apr;108(4):478-98; quiz 499. doi: 10.1038/ajg.2013.4. Epub 2013 Feb 26. — View Citation

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Yang J, Yang X, Wu G, Huang F, Shi X, Wei W, Zhang Y, Zhang H, Cheng L, Yu L, Shang J, Lv Y, Wang X, Zhai R, Li P, Cui B, Fang Y, Deng X, Tang S, Wang L, Yuan Q, Zhao L, Zhang F, Zhang C, Yuan H. Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes. Cell Metab. 2023 Sep 5;35(9):1548-1562.e7. doi: 10.1016/j.cmet.2023.06.010. Epub 2023 Jul 13. — View Citation

Zhang T, Lu G, Zhao Z, Liu Y, Shen Q, Li P, Chen Y, Yin H, Wang H, Marcella C, Cui B, Cheng L, Ji G, Zhang F. Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening. Protein Cell. 2020 Apr;11(4):251-266. doi: 10.1007/s13238-019-00684-8. Epub 2020 Jan 9. — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The mean daily insulin dosage of participants	The mean daily insulin dosage of participants in past week	One-week, Two-week, Four-week post-WMT
Secondary	The Blood glucose of Time in Range (TIR, percent) of type 1 diabetes mellitus.	The proportion of time spent within the target blood sugar range (typically 3.9 to 10.0mmol/L) over a 24-hour period	One-week, Two-week, Four-week post-WMT
Secondary	The SD of blood glucose (SDBG, mmol/L) of type 1 diabetes mellitus.	The standard deviation of measured values during immediate blood glucose monitoring	One-week, Two-week, Four-week post-WMT
Secondary	The largest amplitude of glycemic excursions (LAGE, mmol/L) of type 1 diabetes mellitus.	The range of blood glucose values observed during immediate blood glucose monitoring	One-week, Two-week, Four-week post-WMT
Secondary	The mean amplitude of glycemic excursion (MAGE, mmol/L) of type 1 diabetes mellitus.	After filtering out blood glucose fluctuations below a certain threshold (usually 1 SD), the average fluctuation amplitude is calculated based on the direction of the first significant fluctuation	One-week, Two-week, Four-week post-WMT
Secondary	The mean of daily differences (MODD, mmol/L) of type 1 diabetes mellitus.	The average absolute difference between corresponding measured values over a continuous 48-hour period	One-week, Two-week, Four-week post-WMT
Secondary	The postprandial glucose excursions (PPGE, mmol/L) of type 1 diabetes mellitus.	The average absolute difference between post-meal blood glucose taken 2 hours after three meals and the corresponding pre-meal blood glucose.	One-week, Two-week, Four-week post-WMT
Secondary	The mean blood glucose (MBG, mmol/L) of type 1 diabetes mellitus.	Average values obtained from immediate blood glucose monitoring	One-week, Two-week, Four-week post-WMT
Secondary	The coefficient of variation (CV, percent) of type 1 diabetes mellitus.	CV=(SDBG÷MBG)×100%	One-week, Two-week, Four-week post-WMT
Secondary	The frequency of hypoglycemia or duration of hypoglycemic state in the last 1 week	Hypoglycemia is defined as blood glucose < 3.9 mmol/L	One-week, Two-week, Four-week post-WMT
Secondary	The islet ß-cell function after WMT compared with baseline	2-hour postprandial C-peptide release was used to reflect islet ß-cell function	Three-day, One-week, Two-week, Four-week post-WMT
Secondary	The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0	The severity of AE was graded as mild (grade 1), moderate (grade 2), severe/disabling (grade 3), life threatening (grade 4), and death (grade 5). All AE were divided in definitely, probably and possibly related to treatment. The treatment-related AE we focused on included microbiota-related AEs (e.g., infection, diarrhea, abdominal pain, etc.) and route of delivery related AEs (e.g., nausea, vomiting, etc.)	One-week, Two-week, Four-week post-WMT

External Links

•   Diabetes Facts and Figures. International Diabetes Federation.
•   The top 10 causes of death. World Health Organization.