Washed Microbiota Transplantation for Chronic Constipation in Adults

NCT06106685 | Recruiting Phase 1 DMC

• 1 other identifier: WMT-001-IIT-CC
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single-center, randomized, double-blind, placebo-controlled, dose-exploring clinical study to explore the safety and efficacy of washed microbiota transplantation (WMT) for patients with chronic constipation.

Conditions

Constipation

Keywords

washed microbiota transplantation; constipation; difficult defecation

Outcome Measures

Primary Outcomes (1)

• 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.).

  Two-week post-WMT

Secondary Outcomes (3)

• The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0

  Day 5，Four-week post-WMT，Eight-week post-WMT

• The clinical response rate after treatment

  One-week post-WMT，two-week post-WMT，Four-week post-WMT，Eight-week post-WMT

• The weekly usage rate of assisted defecation drugs.

  One-week post-WMT，Two-week post-WMT, Four-week post-WMT，Eight-week post-WMT

Study Arms (3)

High-dose group

EXPERIMENTAL

The participant will receive a high dose of the washed microbiota suspension, with a bacterial quantity that is 10 times higher than the conventional clinical treatment dose, once daily for a duration of 4 days.

Drug: High-dose washed microbiota suspension

Low-dose group

EXPERIMENTAL

The participant will receive a low-dose washed microbiota suspension, with a bacterial quantity equivalent to the conventional clinical treatment dose. The washed microbiota suspension will be administered once on the first day, followed by placebo of equal volume for the next 3 days.

Drug: Low-dose washed microbiota suspension

Control group

PLACEBO COMPARATOR

The patient will receive a placebo of equal volume once daily for a duration of 4 days.

Drug: Placebo

Interventions

High-dose washed microbiota suspension DRUG

The high-dose group will be administered a high dose of washed microbiota suspension。

Also known as: WMT-001

High-dose group

Low-dose washed microbiota suspension DRUG

The low-dose group will be administered a low dose of washed microbiota suspension.

Low-dose group

Placebo DRUG

The control group will be given equal volume placebo (120ml carrier solution matching the volume of WMT-001), which contains 10% sterile glycerol and saline injection. The drug was administered once a day for 4 days.

Control group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary sign informed consent, age 18-70 years old (including the threshold), male and female.
• For subjects diagnosed with chronic constipation, the duration of the disease is at least 6 months, and the following conditions are met:
• Frequency of spontaneous defecation \<3 times/week (spontaneous defecation refers to spontaneous defecation without the aid of remedial purgatives or manual assistance).
• Dry and hard stool: More than a quarter of the stool is type 1 or 2 on the Bristol Fecal Trait Scale.
• The subject or his/her legal representative has given informed consent, is fully aware of the purpose of the study, is able to communicate well with the investigator, and is able to understand and comply with the requirements of the study.

You may not qualify if:

• Outlet obstruction constipation, such as rectal mucosal prolapse.
• History of abdominal and pelvic surgery, except for no intestinal complications after cholecystectomy, caesarean section, appendectomy, and treatment of intestinal polyps.
• Combined with the colonoscopy results in the past 24 months, patients with intestinal stenosis caused by organic lesions of the digestive tract (such as tumor, inflammation, anal fissure, Crohn's disease, intestinal adhesion, ulcerative colitis, intestinal tuberculosis, etc.) and constipation.
• Other systemic diseases involving the digestive tract (such as neurological diseases (such as Parkinson's disease, spinal cord injury, multiple sclerosis, etc.), muscle diseases (such as amyloidosis, dermatomyositis, etc.), mental disorders (such as depression, etc.), metabolic endocrine disorders (such as diabetes, hypothyroidism, etc.), or constipation caused by opioids.
• Have a history of major surgery or severe trauma within 3 months and have not fully recovered.
• There are contraindications for endoscopic intestinal catheterization via colonic approach, such as severe intestinal stenosis, obstruction, deep ulcer, and high risk of perforation. There are serious ulcers or a large number of false polyps in the fixation area, which is not suitable for fixation. The subject's behavior is seriously out of control.
• Cardiac function and cardiac performance have any of the following abnormalities:
• According to the New York Heart Association (NYHA) heart function rating, the heart function rating is grade III and above.
• Subjects with new myocardial infarction or unstable angina pectoris within 6 months.
• Electrocardiogram indicated prolonged corrected QT interval (QTc) (male QTc≥450ms, female QTc≥470ms).
• Atrial arrhythmias that cannot be stably controlled by drugs and ventricular arrhythmias that require drug control (including grade 2 and above atrioventricular block).
• Poor lung function that the investigator assessed as having an impact on study treatment, such as in subjects with acute chronic obstructive pulmonary disease or long-term oral, intravenous hormone control (other than inhalant/spray hormone use).
• Uncontrolled immune disease and/or the need for long-term use of hormones (except for topical use).
• Subjects with poorly controlled metabolic disease (e.g., thyroid dysfunction) or metabolic disease with gastrointestinal complications (e.g., gastrointestinal autonomic dysfunction, diabetic gastroparesis, etc.);
• Patients with reproductive system diseases (including but not limited to ovarian cysts, endometriosis, primary dysmenorrhea, etc.) that are prone to abdominal pain.

Sponsors & Collaborators

• The Second Hospital of Nanjing Medical University: lead

Study Sites (2)

The second affiliated hospital of Nanjing Medical University

Nanjing, Jiangsu, 210011, China

RECRUITING

the Second Affiliated of Nanjing Medical University

Nanjing, Jiangsu, 210011, China

RECRUITING

Related Publications (13)

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• Zhao YF, Ma XQ, Wang R, Yan XY, Li ZS, Zou DW, He J. Epidemiology of functional constipation and comparison with constipation-predominant irritable bowel syndrome: the Systematic Investigation of Gastrointestinal Diseases in China (SILC). Aliment Pharmacol Ther. 2011 Oct;34(8):1020-9. doi: 10.1111/j.1365-2036.2011.04809.x. Epub 2011 Aug 17.

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• Fleming V, Wade WE. A review of laxative therapies for treatment of chronic constipation in older adults. Am J Geriatr Pharmacother. 2010 Dec;8(6):514-50. doi: 10.1016/S1543-5946(10)80003-0.

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• Gallegos-Orozco JF, Foxx-Orenstein AE, Sterler SM, Stoa JM. Chronic constipation in the elderly. Am J Gastroenterol. 2012 Jan;107(1):18-25; quiz 26. doi: 10.1038/ajg.2011.349. Epub 2011 Oct 11.

  PMID: 21989145 RESULT

• Vazquez Roque M, Bouras EP. Epidemiology and management of chronic constipation in elderly patients. Clin Interv Aging. 2015 Jun 2;10:919-30. doi: 10.2147/CIA.S54304. eCollection 2015.

  PMID: 26082622 RESULT

• Mohaghegh Shalmani H, Soori H, Khoshkrood Mansoori B, Vahedi M, Moghimi-Dehkordi B, Pourhoseingholi MA, Norouzinia M, Zali MR. Direct and indirect medical costs of functional constipation: a population-based study. Int J Colorectal Dis. 2011 Apr;26(4):515-22. doi: 10.1007/s00384-010-1077-4. Epub 2010 Oct 19.

  PMID: 20957375 RESULT

• Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus Polyethylene Glycol for Chronic Constipation. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007570. doi: 10.1002/14651858.CD007570.pub2.

  PMID: 20614462 RESULT

• Chang L, Lacy BE, Moshiree B, Kassebaum A, Abel JL, Hanlon J, Bartolini W, Boinpally R, Bochenek W, Fox SM, Mallick M, Tripp K, Omniewski N, Shea E, Borgstein N. Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System. Am J Gastroenterol. 2021 Sep 1;116(9):1929-1937. doi: 10.14309/ajg.0000000000001334.

  PMID: 34465695 RESULT

• Chey WD, Sayuk GS, Bartolini W, Reasner DS, Fox SM, Bochenek W, Boinpally R, Shea E, Tripp K, Borgstein N. Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation. Am J Gastroenterol. 2021 Feb 1;116(2):354-361. doi: 10.14309/ajg.0000000000000967.

  PMID: 33065589 RESULT

• 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.

  PMID: 31919742 RESULT

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  PMID: 22959620 RESULT

• Schoenfeld P, Lacy BE, Chey WD, Lembo AJ, Kurtz CB, Reasner DS, Bochenek W, Tripp K, Currie MG, Fox SM, Blakesley RE, O'Dea CR, Omniewski ND, Hall ML. Low-Dose Linaclotide (72 mug) for Chronic Idiopathic Constipation: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Am J Gastroenterol. 2018 Jan;113(1):105-114. doi: 10.1038/ajg.2017.230. Epub 2017 Aug 22.

  PMID: 29091082 RESULT

MeSH Terms

Conditions

Constipation

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Faming Zhang

  The Second Hospital of Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Faming Zhang, PhD

CONTACT

086-025-58509883; fzhang@njmu.edu.cn

Bota Cui

CONTACT

086-025-58509884; cuibota@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2023
• First Posted: October 30, 2023
• Study Start: July 24, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 30, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)