Washed Microbiota Transplantation for Diabetic Gastroparesis

Official title

The Efficacy and Safety of WMT in the Treatment of Diabetic Gastroparesis: A Multicenter, Randomized, Double-blind, Placebo-controlled Study

Overview

This is a randomized controlled trial to explore the efficacy and safety of washed microbiota transplantation (WMT) for diabetic gastroparesis (DGP) patients.

Detailed description

At least 44 subjects who meet all the inclusion criteria but do not meet any exclusion criteria will be enrolled in this study. Data of demographic characteristics, Gastroparesis Cardinal Symptom Index (GCSI), Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), Gastroparesis Core Symptom Daily Diary (GCS-DD), Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QoL), and clinical outcomes will be collected. After treatment, they will enter the follow-up period for efficacy and safety evaluation.

Interventions

• Other washed microbiota transplantation
  Washed microbiota transplantation refers to the infusion of washed microbiota from healthy donor into patients' gastrointestinal tract. Participants will receive two doses of WMT for DGP.
• Other placebo
  A carrier fluid with matching volume and consistent appearance to the infusion of washed microbiota.

Primary outcome measures

• Response rate of DGP after WMT [Time frame: Four-week post-WMT]

Secondary outcome measures (9)

• The extent of change observed in GCSI of participants; [Time frame: One-week, Two-week and Eight-week post-WMT]
• The extent of change observed in Gastroparesis Core Symptom Daily Diary (GCS-DD) of participants; [Time frame: One-week, Two-week, Four-week and Eight-week post-WMT]
• The extent of change observed in Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) of participants; [Time frame: One-week, Two-week, Four-week and Eight-week post-WMT]
• The extent of change observed in Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QoL) of participants; [Time frame: One-week, Two-week, Four-week and Eight-week post-WMT]
• The extent of change observed in electrogastrogram (EGG) of participants; [Time frame: One-week, Two-week, Four-week and Eight-week post-WMT]
• The extent of change observed in electrogastrogram (EGG) of participants; [Time frame: One-week, Two-week, Four-week and Eight-week post-WMT]
• The extent of change observed in gastrointestinal ultrasound (GIUS) of participants; [Time frame: One-week, Two-week, Four-week and Eight-week post-WMT]
• The incidence rate of adverse events; [Time frame: One-week, Two-week, Four-week and Eight-week post-WMT]
• The changes in gut microbiota composition and metabolites before and after treatment. [Time frame: One-week, Two-week, Four-week and Eight-week post-WMT]

Eligibility criteria

Inclusion criteria

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

• Diagnosed with diabetes for over 1 year;
• Accompanied by symptoms such as abdominal bloating, early satiety, persisting for at least 3 months, with a GCSI Total Score greater than/equal to 2.3;
• Objective evidence of delayed gastric emptying within the past 3 months, including but not limited to scintigraphic gastric emptying or gastric ultrasound;
• Upper gastrointestinal obstructive lesions were ruled out by imaging or endoscopic examination within the past 3 months;
• Males and nonpregnant, non-breastfeeding females who are aged more than 18 years and sign the informed consent form;
• The subject or his/her legal representative gives informed consent, fully understands 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:

Subjects who:

• Have any upper gastrointestinal pathology other than diabetic gastroparesis that would require therapy other than that provided in this trial;
• Have a prior history of gastric surgery, including but not limited to gastric bypass, gastrectomy, gastric banding, pyloroplasty, fundoplication, or vagotomy in past 1 year;
• Have any organic/neurological disease that is suspected to be causing gastroparesis, other than diabetes;
• Have been using medications affecting gastrointestinal motility, such as GLP-1 agonists;
• Have contraindications for intestinal tubing;
• Have a history of medication that regulate intestinal microbiome in last 48 hours;
• Have serious diabetic complications need immediately be dealt, such as diabetic ketoacidosis
• Have poor lung function and those deemed by the investigator to be affected by the study treatment, such as during COPD exacerbations;
• Have any of the following abnormalities in cardiac function and cardiac performance:

• Cardiac function rating≥Ⅲ according to New York Heart Association (NYHA);
• New myocardial infarction or unstable angina pectoris within 6 months;
• Electrocardiogram indicated prolonged QTc interval (male QTc≥450ms, female QTc≥470ms);
• requiring drug intervention (more than Ⅱ atrioventricular block).
• Have preexisting hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points);
• Kidney disease with KDIGO stage 3b (GFR<45 ml/min/1.73m2) or above;
• Have infectious diseases such as active hepatitis (requiring long-term use of drugs), HIV or active tuberculosis;
• Have a history of drug abuse, alcoholism (defined as consuming more than 14 units per week, with 1 unit equivalent to 360 mL of beer, 45 mL of 40% alcohol, or 150 mL of wine), or substance misuse;
• Other significant systemic illnesses, such as malignant tumors;
• Have other situations in which the investigator deems it inappropriate to participate in this study.

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

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affi — Nanjing

Publications

• Shin AS, Camilleri M. Diagnostic assessment of diabetic gastroparesis. Diabetes. 2013 Aug;62(8):2667-73. doi: 10.2337/db12-1706. No abstract available. PMID 23881199
• Ye Y, Jiang B, Manne S, Moses PL, Almansa C, Bennett D, Dolin P, Ford AC. Epidemiology and outcomes of gastroparesis, as documented in general practice records, in the United Kingdom. Gut. 2021 Apr;70(4):644-653. doi: 10.1136/gutjnl-2020-321277. Epub 2020 Jun 3. PMID 32493829
• Aswath GS, Foris LA, Ashwath AK, Patel K. Diabetic Gastroparesis(Archived). 2023 Mar 27. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK430794/ PMID 28613545
• 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. PMID 36817869
• Camilleri M, Kuo B, Nguyen L, Vaughn VM, Petrey J, Greer K, Yadlapati R, Abell TL. ACG Clinical Guideline: Gastroparesis. Am J Gastroenterol. 2022 Aug 1;117(8):1197-1220. doi: 10.14309/ajg.0000000000001874. Epub 2022 Jun 3. PMID 35926490
• Vosoughi K, Ichkhanian Y, Benias P, Miller L, Aadam AA, Triggs JR, Law R, Hasler W, Bowers N, Chaves D, Ponte-Neto AM, Draganov P, Yang D, El Halabi M, Sanaei O, Brewer Gutierrez OI, Bulat RS, Pandolfino J, Khashab M. Gastric per-oral endoscopic myotomy (G-POEM) for refractory gastroparesis: results from an international prospective trial. Gut. 2022 Jan;71(1):25-33. doi: 10.1136/gutjnl-2020-322756 PMID 33741641
• Ragi O, Jacques J, Branche J, Leblanc S, Vanbiervliet G, Legros R, Pioche M, Rivory J, Chaussade S, Barret M, Wallenhorst T, Barthet M, Kerever S, Gonzalez JM. One-year results of gastric peroral endoscopic myotomy for refractory gastroparesis: a French multicenter study. Endoscopy. 2021 May;53(5):480-490. doi: 10.1055/a-1205-5686. Epub 2020 Jul 21. PMID 32575130
• Martinek J, Hustak R, Mares J, Vackova Z, Spicak J, Kieslichova E, Buncova M, Pohl D, Amin S, Tack J. Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: a pilot, randomised, sham-controlled trial. Gut. 2022 Nov;71(11):2170-2178. doi: 10.1136/gutjnl-2022-326904. Epub 2022 Apr 25. PMID 35470243

Identifiers

NCT: NCT06340217 · WMT-GDP-RCT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗