Levofloxacin in the Treatment of Chronic Functional Constipation Associated With PIB(Peristaltic Contraction-Inhibiting Bacterium) Infection
NCT Number: NCT06571097
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Constipation
Interventions: DRUG: Levoﬂoxacin
Sponsor: Haifeng Lan
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 50
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-01
Completion Date: 2025-06
Locations: Levofloxacin in the Treatment of Chronic Functional Constipation Associated With PIB Infection: A Multi-center, Exploratory Clinical Study, Nanjing, Jiangsu, 210000, China

Summary:
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.

Primary Outcome Measures: 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: 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