Clinical trial NCT03656328: Supplementation With Lacobacillus Reuteri ATCC PTA 4659 in Patients Affected by Acute Uncomplicated Diverticulitis
Official title: Supplementation With Lacobacillus Reuteri ATCC PTA 4659 in Patients Affected by Acute Uncomplicated Diverticulitis : a Randomized Double-blind Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Diverticulitis
Keywords: probiotics
inflammation markers
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2018-09-04
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind
Primary purpose: TREATMENT

Brief summary: Acute Uncomplicated Diverticulitis (AUD) is defined as inflammation of the colon diverticulum, often involving the colic wall and pericolic fat. In a double-blind RCT study, the investigators tested the efficacy of Lactobacillus reuteri ATCC PTA 4659 (L. reuteri), a specific strain with anti-inflammatory effect in association with conventional antibiotics, in treating AUD, compared with conventional antibiotic therapy plus placebo. A primary outcome was reduced abdominal pain and inflammatory markers (C-RP) in the group treated with L. reuteri compared with the placebo. A secondary outcome was reduced hours of hospitalization in the L. reuteri group.

A double-blind, placebo RCT was conducted with 90 consecutive patients with a diagnosis of AUD treated at the Emergency Department of Foundation Poli-clinico A. Gemelli Hospital. Following a routine blood test and determination of C-reactive protein (C-RP) value, all patients were admitted to the Brief Observation Unit (BOU) and randomly as-signed to two groups:

* Group A : Treated with ciprofloxacin 400 mg twice a day and metronidazole 500 mg three times a day for one week, plus supplementation with L. reuteri twice a day for 10 days.
* Group B : Treated with the same antibiotic therapy as Group A for one week, plus placebo twice a day for 10 days.

All patients completed a daily Visual Analog Scale (VAS) for abdominal pain, with a range from 0 (asymptomatic) to 10. C-RP value was determined again at 72 hours.

Detailed description: Patients are evaluated in a clinical setting by a physician at enrolment in the study, every day during hospitalization, and at the end of therapy. At enrolment, a medical history review (including drugs taken), physical examination, laboratory tests (blood cell count, hepatic and renal function, electrolytes, C-RP) and abdominal CT scan were performed.

All patients presented with AUD (Hinchey classification grade 0). All patients were given a Visual Analog Scale (VAS) ranging from 0 to 10, where 0 is asymptomatic and 10 is the worst pain they could have, to complete during the 10 days of the study.

Patients were also asked to complete a diary, in order to record any 'adverse experience' (causing discomfort and/or interrupting the subject's usual activity) during the treatment periods, and to record every time they did not consume the prescribed doses. The diary was analyzed by physicians.

The patients are randomly assigned into two groups, according to an automatically generated randomization list in a 1:1 ratio, using statistical software:

Group A received standard antibiotic therapy, consisting of ciprofloxacin 400 mg twice a day and metronidazole 500 mg three times a day for seven days, with supplementation with the probiotic L. reuteri 4659 twice a day for 10 days.

Group B received the same standard antibiotic therapy as group A and a matching placebo for the same periods.

Patients were informed by an investigator (blind) that such a supplement could help in improving the inflammation associated with diverticulitis. Boxes containing placebo had the same shape dimensions, and trade mark indication and contained the same amount of capsules as L. reuteri boxes, and they were provided by the same probiotic producer.

The supplement of L. reuteri 4659 was administered in a dose of 108 colony-forming units (CFU), in capsules 30 minutes after food. During the study period, patients were instructed to store the product according to the recommended temperature. In particular, the capsules could be stored at room temperature (25°C). Because L. reuteri is a living organism, over long storage periods it is preferable not to freeze the capsules, but to refrigerate them at 2-8°C.

Eligibility criteria: Inclusion Criteria:

* Age \>18 years
* No reported allergies to contrast agents or antibiotics
* Informed consent
* Diagnosis of AUD confirmed by abdomen CT scan

Exclusion Criteria:

* \<18 years
* Pregnancy or breastfeeding
* Concomitant or recent (7-10 days) participation in another clinical trial
* Concomitant or recent (7-15 days) intake of probiotics or antibiotics
* Major concurrent diseases (hepatological, renal, tumor)
* Inflammatory bowel disease (Crohn's disease, ulcerative colitis) or other organic gastrointestinal disease
* Allergies to contrast agents or antibiotics
* Mental illness or inability to adhere to protocols.

Primary outcomes:
measure: reduction of abdominal pain
timeFrame: 10 days
Secondary outcomes:
measure: reduction of inflammatory markers
timeFrame: 72 hours
measure: comparisons of hours of hospitalization
timeFrame: 5 days
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Policlinico universitario agostino gemelli
Study officials:
affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Veronica Ojetti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Petruzziello C, Migneco A, Cardone S, Covino M, Saviano A, Franceschi F, Ojetti V. Supplementation with Lactobacillus reuteri ATCC PTA 4659 in patients affected by acute uncomplicated diverticulitis: a randomized double-blind placebo controlled trial. Int J Colorectal Dis. 2019 Jun;34(6):1087-1094. doi: 10.1007/s00384-019-03295-1. Epub 2019 Apr 22.