Role Of Lactobacillus Reuteri DSM 17938 In The Non-Complicated Diverticular Disease (ReDiCo)

Phase 3 Study of Lactobacillus Reuterii in Patients With Symptomatic Non-complicated Diverticular Disease

The aim of this study is to evaluate the effectiveness and the tolerability of the Lactobacillus reuteri in the control of the diverticular disease symptoms and in the prevention of acute diverticulitis episodes.

Study Overview

• Status: Unknown
• Conditions: Diverticulitis; Diverticulosis
• Intervention / Treatment: Dietary supplement: placebo; Dietary supplement: Lactobacillus Reuterii

Detailed Description

The gastrointestinal apparatus hosts a bacterial population that quantifies to around 1011 microorganisms per gram of content with more than 400 different species. Its principal functions are: metabolic, trophic, and protective. The Lactobacillus reuteri (Reuterin®) is considered one of the few native species in the human intestinal tract. It is able to modulate the immune response CD4+ T-Helper to an ileum level. Lactobacillus reuteri isolated for the first time in 1980 is a heterofermantative species. Its probiotic activity is attributed to the ability to exercise an inhibitive effect on the pathogenic micro-organisms with a combination of mechanisms including the production of lactic acid, hydrogen peroxide, antimicrobic substances and bactericide. Moreover, Lactobacillus reuteri is in a position to produce various short chain-like fat acids such as the acetic acid from the fermentation of carbohydrates. At last, it is in a position to produce a powerful antimicrob substance known as Reuterina that is capable of inhibiting the growth of many bacterial species including Escherichia, Salmonella, Shigella, Proteus, Pseudomonas, Clostridium and Sfafilococcus as well as fungi and protozoa, many of which are pathogens for man.

Among pathologies in which it is hypothesized that probiotics could have a possible therapeutic role, there is the diverticulosis disease. Approximately 20% of patients with colonic diverticula have intestinal disturbances and a reduction of the quality of life. Moreover approximately 20% of the patients with diverticulosis in the colon have at least 1 acute diverticulitis attack, characterized by pain, fever, abdominal defence, increment of the VES and neutrophil leucocytosis. Usually the acute diverticulitis episode can be controlled by medical therapy, but repeated episodes in time often lead to greater complications in the perforation, from the abdominal abscesses, from the fistulas and from the stenosis. The prevention of acute diverticulitis episodes is therefore very important so as to prevent greater complications of such pathology.

Until now, the scientific evidences have suggested the use of fibre and non-absorbable antibiotics (such as rifaximine) for the treatment of a non-complicated diverticular disease and for the prophylaxis of the feared complications. The extended use of antibiotics exposes to the risk of selecting resistant strains and there are no long-term studies on the outcome of the patients suffering from diverticulosis in continuous therapy with rifaximine and fibres. The therapy with Lactobacillus reuteri could be effective in the control of symptoms of the diverticular disease through its trophic action on coloncytes (thanks to the SCFA production), both through the modulation of the activity of the immune system and on the intestinal permeability. Moreover the antibacterial activity of Lactobacillus reuteri against the pathogenic bacteria could be useful in the prevention and the treatment of acute diverticulitis episodes. Finally, thanks to its trophic role on the intestinal epithelium, Lactobacillus reuteri could help the mucosal cure of acute diverticulitis episodes.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Florence, Italy, 50141
    • Not yet recruiting
    • Careggi Hospital
    • Contact: Vito Annese, MD; Phone Number: 00390557946035; Email: annesev@aou-careggi.toscana.it
    • Principal Investigator: Vito Annese, MD
  • San Giovanni Rotondo, Italy, 71013
    • Recruiting
    • Casa Sollievo della Sofferenza Hospital - IRCCS
    • Contact: Fabrizio Bossa, MD; Phone Number: 00390882410235; Email: f.bossa@operapadrepio.it
    • Contact: Angelo Andriulli, MD; Phone Number: 00390882410263; Email: a.andriulli@operapadrepio.it
    • Sub-Investigator: Fabrizio Bossa, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients affected by symptomatic diverticulosis
• Informed consent obtained and signed.
• Expected compliance

Exclusion Criteria:

• Patients supplemented with other probiotics
• Patients treated with antibiotics
• Patients affected by hearth failure, renal failure, neoplasia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: placebo; placebo
Active Comparator: Lactobacillus Reuterii	Dietary supplement: Lactobacillus Reuterii; Lactobacillus Reuterii 10000000000 CFU per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of 50% of the score of activity of the diverticular disease	A validated questionnaire was used to investigate on intestinal symptoms. The following symptoms/signs will be investigated: Abdominal pain; Abdominal bloating; Urgency; Diarrhoea; Abdominal Tension Each factor previously listed will be graded according to the following scale of gravity: 0= no symptom; 1= light disturbance; 2= moderate disturbance; 3= serious disturbance The score of activities can range between 0 (asymptomatic patient) to 15 (serious disturbances with important impacts on the quality of life).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of 20% of acute diverticulitis episodes	To value the efficancy in reduction of acute diverticulitis, defined as episodes of abdominal pain associated with fever and/or abdominal resistance, increment of ESR and neutrophil leucocitosis and that demand a treatment of systemic antibiotics	1 year

Collaborators and Investigators

• Sponsor: Casa Sollievo della Sofferenza IRCCS
• Collaborators: Careggi Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: July 22, 2010
• First Submitted That Met QC Criteria: July 22, 2010
• First Posted (Estimate): July 23, 2010

Study Record Updates

• Last Update Posted (Estimate): June 28, 2011
• Last Update Submitted That Met QC Criteria: June 27, 2011
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: Probiotics; Diverticulitis; Diverticular disease; Diverticula
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Pathological Conditions, Anatomical; Diverticulitis; Diverticulum; Diverticular Diseases
• Other Study ID Numbers: ReDiCo