Effect of Antibiotic Pretreatment on the Efficacy of WMT in the Treatment of Chronic Constipation

Effect of Antibiotic Pretreatment on the Efficacy of WMT in the Treatment of Chronic Constipation in Adults: a Multi-center, Randomized, Placebo-controlled Clinical Study

This is a randomized controlled trial to explore the efficacy of antibiotic pretreatment on the efficacy of WMT in the treatment of chronic constipation in adults: a multi-center, randomized, placebo-controlled clinical study

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Constipation
• Intervention / Treatment: Drug: Ornidazole; Drug: Placebo

Detailed Description

All included in the standard but do not accord with standard of any rule out subjects will be included in this study. Demographic characteristics, complete spontaneous bowel movements（CSBM), Constipation assessment scale (CAS), Patient-Assessment of Constipation Quality Of Life（PAC-QOL) and clinical outcomes were collected. After the treatment, the efficacy and safety were evaluated during the follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Faming Zhang, PhD; Phone Number: 086-025-58509883; Email: fzhang@njmu.edu.cn
• Study Contact Backup: Name: Bota Cui; Phone Number: 086-025-58509884; Email: cuibota@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

1. Male and female, aged ≥18 years old, provided written informed consent;
2. Subjects diagnosed with chronic constipation, with a duration of at least 6 months, and with the following conditions:

1) spontaneous bowel movement frequency <3 times/week (spontaneous bowel movement was defined as spontaneous bowel movement without rescue laxatives or manual assistance); 2) waste hard: at least 25% of defecation in Bristol stool traits scale type 1 or 2.

3. The subjects or their legal representatives gave informed consent, fully understood the purpose of the study, were able to communicate well with the researchers, and understood and complied with the requirements of the study.

Exclusion Criteria:

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

1. Presence of outlet obstruction and constipation, such as rectal mucosal prolapse
2. Combined with the results of colonoscopy in the past 24 months, those with intestinal stenosis caused by organic lesions of the digestive tract (such as tumor, inflammation, anal fissure, Crohn's disease, ulcerative colitis, intestinal adhesion, intestinal tuberculosis, etc.) and constipation;
3. Constipation caused by other systemic diseases involving the digestive tract, such as nervous system 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 and endocrine disorders (such as diabetes, hypothyroidism, etc.) or opioids, etc.
4. Has a history of abdominal pelvic surgery, but after cystic resection, cesarean section, does not appear after appendectomy postoperative intestinal complications, and intestinal polyps except after treatment;
5. Has a history of major surgery within 3 months or a history of severe trauma, and recovery is not completely;
6. There are contraindications to colonic transendoscopic intestinal tube implantation, such as severe intestinal stenosis, obstruction, deep ulcer, and high risk of operation perforation; Severe ulcers or a large number of pseudopolyps exist in the fixed area of titanium clips, which are not suitable for fixation. The subjects' behavior was seriously uncontrolled.

7. Any of the following abnormalities in cardiac function and performance:

   1. According to the New York Heart Association (NYHA) cardiac function classification, cardiac function grade Ⅲ or above;
   2. new onset myocardial infarction or unstable angina pectoris within 6 months;
   3. ECG showed QTc prolongation (QTc≥ 450ms in men and ≥470ms in women);
   4. Drug-refractory atrial arrhythmias and drug-refractory ventricular arrhythmias (including grade 2 or higher atrioventricular block).
8. Patients with poor lung function that is considered by the investigator to have an impact on the study treatment, such as patients with acute exacerbation of COPD or patients requiring long-term use of oral or intravenous steroids for control (except inhalers/sprays);
9. No control autoimmune disease and/or need long-term use of hormone (except local external use sex);
10. Patients with metabolic diseases and poorly controlled by drugs (such as thyroid dysfunction), or patients with metabolic diseases accompanied by gastrointestinal function complications (such as gastrointestinal autonomic nerve dysfunction, diabetic gastroparesis, etc.);
11. Suffering from reproductive system diseases (including but not limited to ovarian cysts, endometriosis, primary dysmenorrhea, etc.) that may lead to abdominal pain;

12. Significant laboratory abnormalities that, in the judgment of the investigator, may affect the safety of the subjects or the completion of the clinical study, including:

    A) the hemoglobin < 100 g/L; B) Serum creatinine ≥1.5 times the upper limit of normal (ULN) C) abnormal liver function, defined as AST>1.5×ULN and/or ALT>1.5×ULN and/or total bilirubin >1.5×ULN; D) blood clotting function: PLT acuities were 80 x 109 / L, APTT > 1.5 x ULN, PT > 1.5 x ULN, INR > 1.5 x ULN; E) abnormal results or defecate occult blood stool and has prompted the clinical significance of the gastrointestinal tract.

13. Have active hepatitis (requiring or taking long-term treatment), HIV, or active tuberculosis;
14. A history of drug or alcohol abuse (i.e., drinking more than 14 servings per week of beer, 45 mL of 40% spirits, or 150 mL of wine) or substance abuse;
15. The known allergic to research similar drugs, drugs or accessories;
16. Use of anti-infective drugs (antibiotics, antifungal, antiviral) within 14 days before enrollment, or need anti-infective treatment at enrollment evaluation;
17. Drugs and supplements that affect gastrointestinal motility and function cannot be stopped during the study, including but not limited to: antibiotics such as erythromycin; Drugs that modulate the intestinal microecology, such as probiotics such as Bifidobacterium; The parasympathetic nerve inhibitors, some scopolamine and atropine, belladonna, etc; Muscle relaxants, such as succinylcholine; Antidiarrheal agents such as loperamide, smecta; Opioid preparations; Drugs that inhibit gastric acid secretion;
18. Pregnant or lactating women, or refusing to use an effective contraceptive method within 3 months after the last dose of treatment;
19. 3 months prior to dosing involved in drug interventional clinical trials;
20. Suffering from malignant tumors;
21. There were other circumstances that the investigator considered inappropriate for participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Patients will receive three enemas of ornidazole 0.5g+50ml saline through the TET tube, followed by WMT once daily for a duration of 3 days.	Drug: Ornidazole; Patients will receive three consecutive enemas of ornidazole 0.5g+50ml saline through the TET tube, followed by WMT treatment once daily for a duration of 3 days; Other Names: washed microbiota transplantation
Placebo Comparator: Control; Patients will receive three enemas of a placebo of equal volume through the TET tube, followed by WMT once daily for a duration of 3 days.	Drug: Placebo; Patients will receive three consecutive enemas of placebo of equal volume through the TET tube, followed by WMT treatment once daily for a duration of 3 days; Other Names: washed microbiota transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate of complete spontaneous bowel movements（CSBM）	Overall CSBM respondents defined in the study of drug treatment in patients with the number of weeks of at least 50% of the time meet the CSBM weeks response week (4/8). Response was defined as a CSBM of at least three times in the week and an increase of at least one CSBM from baseline. CSBM was defined as the number of voluntary bowel movements with complete defecation sensation without taking remedial laxatives or manual assistance.	One-week, Four-week and Eight-week post-WMT
The extent of change observed in Constipation assessment scale (CAS) of participants	The CAS consisted of 8 items, including abdominal distension, changes in exhaust volume, decreased frequency of defecation, watery stool, rectal obstruction or pressure, rectal pain during defecation, thinness of stool, and unsuccessful defecation. Each item was scored from 0 to 2 according to the severity of symptoms. Each item score was summed, with 0 as no constipation and 16 as the most severe constipation.	One-week, Four-week and Eight-week post-WMT
The extent of change observed in Patient-Assessment of Constipation Quality Of Life（PAC-QOL）of participants	The Constipation Quality of Life Scale (PAC-QOL) contains 28 items, including physical discomfort, anxiety, psychosocial discomfort, and satisfaction. It reflects the impact of constipation on daily life in the past two weeks.	One-week, Four-week and Eight-week post-WMT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The extent of change observed in stool properties of participants	Bristol stool form scale(BSFS) was used, which can be divided into seven types.	One-week post-WMT
Rate of Adverse Events	The rate of adverse events after antibiotic pretreatment	One-week, Four-week and Eight-week post-WMT

Collaborators and Investigators

• Sponsor: Faming Zhang
• Investigators: Principal Investigator: Faming Zhang, PhD, The Second Hospital of Nanjing Medical University

Publications and helpful links

General Publications

• Keshteli AH, Millan B, Madsen KL. Pretreatment with antibiotics may enhance the efficacy of fecal microbiota transplantation in ulcerative colitis: a meta-analysis. Mucosal Immunol. 2017 Mar;10(2):565-566. doi: 10.1038/mi.2016.123. Epub 2016 Dec 21. No abstract available.
• Singh P, Alm EJ, Kelley JM, Cheng V, Smith M, Kassam Z, Nee J, Iturrino J, Lembo A. Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D. Gut Microbes. 2022 Jan-Dec;14(1):2020067. doi: 10.1080/19490976.2021.2020067.
• Khalif IL, Quigley EM, Konovitch EA, Maximova ID. Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation. Dig Liver Dis. 2005 Nov;37(11):838-49. doi: 10.1016/j.dld.2005.06.008. Epub 2005 Oct 5.
• Bazzocchi G, Giovannini T, Giussani C, Brigidi P, Turroni S. Effect of a new synbiotic supplement on symptoms, stool consistency, intestinal transit time and gut microbiota in patients with severe functional constipation: a pilot randomized double-blind, controlled trial. Tech Coloproctol. 2014 Oct;18(10):945-53. doi: 10.1007/s10151-014-1201-5. Epub 2014 Aug 5.
• Xu J, Xu H, Guo X, Zhao H, Wang J, Li J, He J, Huang H, Huang C, Zhao C, Li Y, Zhou Y, Peng Y, Nie Y. Pretreatment with an antibiotics cocktail enhances the protective effect of probiotics by regulating SCFA metabolism and Th1/Th2/Th17 cell immune responses. BMC Microbiol. 2024 Mar 18;24(1):91. doi: 10.1186/s12866-024-03251-2.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: May 20, 2024
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 24, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: randomized controlled trial; chronic constipation; washed microbiota transplantation; transendoscopic enteral tube; antibiotic pretreatment
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Antitrichomonal Agents; Ornidazole
• Other Study ID Numbers: WMT-Anti-CC-202405

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No