Levofloxacin in the Treatment of Chronic Functional Constipation Associated With PIB(Peristaltic Contraction-Inhibiting Bacterium) Infection

Levofloxacin in the Treatment of Chronic Functional Constipation Associated With PIB Infection: A Multi-center, Exploratory Clinical Study

Constipation, a prevalent clinical condition, significantly impacts patients' quality of life, yet relevant clinical trial technical guidelines have yet to be issued domestically. This disease encompasses various classifications based on etiology, pathology, and pathophysiological characteristics. Slow transit constipation (STC), specifically, arises from colonic motility disorders and is recognized as a neuromuscular colonopathy. Currently, limited therapeutic options are available for patients with refractory STC, rendering it a common ailment associated with substantial disease burden and uncertain etiology. Consequently, identifying the cause and developing effective, targeted, and safe treatment strategies is of paramount importance.

Our research team has made a groundbreaking international discovery, revealing that STC is caused by infection with a novel Shigella-like bacterium, termed the peristaltic contraction-inhibiting bacterium (PIB), which secretes docosapentaenoic acid (DPA), an unsaturated fatty acid. The pathogenic mechanism involves inhibition of intestinal peristalsis, subsequently slowing colonic transit. Preliminary epidemiological studies confirm the exclusive presence of PIB in feces from patients with intractable constipation, whereas it is virtually absent in healthy individuals. Notably, consumption of high-dose DPA does not affect colonic transit or induce constipation; however, intracolonic administration does.

In response to PIB-induced STC, our team screened a range of antibiotics and identified two primary classes with potent antibacterial effects against PIB: fluoroquinolones and carbapenems. Both classes exhibit strong inhibitory activity against PIB, suggesting their potential use in chronic constipation treatment. Levofloxacin, a quinolone antibiotic, possesses broad-spectrum and potent antibacterial properties, effective in treating intestinal and urinary tract infections. Given that PIB has been confirmed as a novel Shigella-like species, and quinolones are established as the first-line antibiotics for Shigella infections, levofloxacin's efficacy against PIB was anticipated. Preliminary studies have validated levofloxacin's ability to inhibit PIB growth, thereby alleviating PIB-induced refractory constipation through sensitivity testing.

The primary objective of this study is to utilize levofloxacin to suppress PIB, thereby achieving the relief of chronic functional constipation.

Study Overview

• Status: Recruiting
• Conditions: Constipation
• Intervention / Treatment: Drug: Levofloxacin

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ji Xuan; Phone Number: 02580864222; Email: helio0009@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • Levofloxacin in the Treatment of Chronic Functional Constipation Associated With PIB Infection: A Multi-center, Exploratory Clinical Study
      • Contact: haifeng Lan; Phone Number: 15718548312; Email: 2410329972@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants must meet all of the following criteria to enter the trial.

1. Signed written informed consent;
2. Age 18-70;
3. Diagnosed chronic functional constipation according to Rome III or IV criteria, and infected with PIB;
4. Patients who have not taken other types of antibiotics in the past 1 month;
5. Bowel organic lesions (tumors and severe inflammatory lesions, etc.) were excluded by colonoscopy in the past 2 years.
6. The subjects could follow the follow-up plan, objectively describe the symptoms, and cooperate with the completion of the scale; 7）Agree to maintain similar diet and activity levels from the screening visit to the end of the study;

Exclusion Criteria:

Exclusion criteria: Subjects must exclude all of the following conditions to enter the study.

1. Pregnant and lactating women;
2. Patients with drug-induced constipation, including constipation induced by opioids and antidepressants;
3. During the study period, changes in lifestyle and dietary habits are not recommended in principle;
4. Patients with diseases that affect the conduct or results of the study, such as mental illness, serious cardiopulmonary, liver and kidney diseases, history of gastrointestinal surgery, epilepsy, etc.
5. Those who cannot take samples and complete inspection items as required;
6. Allergic to levofloxacin; 7）Other researchers found it inappropriate to participate in the project for clinical manifestations or diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levofloxacin; Levofloxacin: 0.5g(500mg)/day for 2 weeks	Drug: Levofloxacin; 0.5g/day for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total effective rate of levofloxacin in the treatment of chronic functional constipation.	Obvious effect: no defecation difficulty, the number of spontaneous defecation ≥3 times/week (no effort and time consuming when defecating, no feeling of inadequate defecation, normal stool characteristics, etc.); Effective: the difficulty of defecation is improved than before, and the number of autonomous defecation is not less than 3 times/week (one of the time-consuming and laborious defecation or improper defecation or abnormal stool characteristics occurs during defecation);Ineffective: The difficulty of defecation is no better than before, and the number of spontaneous defecation is less than 3 times/week.Total effective rate = (significant efficiency + effective rate) Number of cases/total number of cases ×100%.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PIB concentration (DPA content of docosapentaenoic acid)	PIB concentration ( DPA content in intestinal stool)	6 months
Proportion of patients with first defecation	Proportion of patients with complete spontaneous defecation within 24-48 hours after receiving the first dose	24-48 hours
Time of first defecation	The time of patients with complete spontaneous defecation within 24-48 hours after receiving the first dose.	24-48 hours
Number of frequency of use of rescue drugs and other Other defecation medications per week	Number of frequency of use of rescue drugs and other Other defecation medications per week	6 months
PAC-SYM	PAC-SYM（Patient Assessment of Constipation symptom）	6 months
PAC-QoL scale	PAC-Qol (Quality of life scale）	6 months
Bristol scale	Bristol (stool property)	6 months
The incidence of serious adverse events	intestinal obstruction, hematochezia, elevated indicators of serious infection, severe bloating, diarrhea, etc.	6 months
Patient satisfaction with treatment survey	Satisfaction degree of patients with levofloxacin treatment of constipation symptoms	6 months

Collaborators and Investigators

• Sponsor: Haifeng Lan

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 23, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: August 23, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Levofloxacin; constipation; PIB; Peristaltic Contraction-Inhibiting Bacterium
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Levofloxacin
• Other Study ID Numbers: DZQH-KYLL-24-20

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