Effect of a Probiotic on Diverticular Symptoms
Effect of a Probiotic on Diverticular Symptoms
Diverticulitis is an extremely common digestive disease particularly found in the large
 intestine in elderly patients and develops from diverticulosis. Diverticulosis is
 characterized by the formation of pouches (diverticula) that bulge to the outside of the
 colon, through areas of weakness in the colonic wall. Inflammation (diverticulitis) results
 if one of these diverticula becomes infected and / or obstructed. It is commonly accompanied
 by obvious or microscopic perforation, ranging in severity from a single, mild, acute attack
 of diverticulitis to more severe attacks characterized by abscess formation, occasionally
 resulting in chronic complications such as obstruction and fistula formation. After an
 episode of diverticulitis many patients develop changes in bowel openings, from diarrhoea and
 constipation, and many patients have abdominal pain and a symptom complex that resembles
 Irritable Bowel Syndrome (IBS).

 According to available guidelines, treatment of symptomatic, but uncomplicated, diverticular
 disease aims to reduce the frequency and severity of diverticular related symptoms (abdominal
 pain, bloating, alterations in bowel habit) and to prevent complications. Different agents
 have been proposed, such as bulking agents, antispasmodics, and nonabsorbed topical
 antibiotics, 5amino acid preparations but these measures are unproven or controversial. It is
 thought that intestinal bacteria may play a significant role in the symptoms of
 post-diverticulitis.

 The investigators have recently shown that a probiotic (Symprove) reduced the symptoms of IBS
 significantly in comparison with a placebo in a double-blind randomized trial and without
 side effects (paper in preparation). Because the symptoms in IBS and post-diverticulitis are
 so similar the investigators propose a double-blind placebo controlled trial of Symprove in
 patients with problematic diverticulitis. Patients will be recruited from a dedicated
 diverticulitis clinic using standard exclusion criteria. This is a 90 day symptom based trial
 using accepted outcome measures. If successful the results will have widespread implications
 for treatment of diverticular disease.
The patients for this study will be recruited from the diverticular disease clinic at King's
 College Hospital. The clinic is the first and the largest specialist diverticular clinic in
 the UK and attracts referrals directly from GP's, internal referrals from gastroenterology,
 in and outpatients and increasingly from Gastroenterology and Colorectal Surgery clinics in
 the South East of England. Eligible patients who meet fulfill the entry criteria will be
 invited to participate. They will receive a patient information sheet, which they take home
 with them for reading. They will then be seen again (usually within 2 weeks, or after any
 confirmatory tests have been completed) to discuss any questions that they may have and for a
 decision for inclusion into the trial.

 Each will undergo a full blood count and conventional biochemistry and they will provide a
 stool sample for assessment of intestinal inflammation by a calprotectin estimation. They
 will also complete a baseline symptoms-based questionnaire. They will then be randomized to
 treatments A or B, both investigator and patient will be unaware of whether it is the active
 treatment (Symprove) or placebo. Each patient will complete the symptom-based questionnaire
 every 30 days while on on the 90 day treatment (Day 30, Day 60, and Day 90). The primary
 outcome measure will be a change in symptoms score from Day 0 to Day 90.

 Also every 30 days while on treatment, stool tests will be repeated for faecal calprotectin.
 An additional sample will be frozen for eventual microbiota assessment. The secondary outcome
 measure will be change in the faecal microbiota between Day 0 and Day 90.

 Patients will be seen in clinic 30 days after cessation of the trial (Day 120), at which time
 those patients on placebo will be offered a 90 day free treatment with the active ingredient
 if they so wish.
Inclusion Criteria:

 -  Have a documented episode of diverticulitis as assesses clinically, on CT scans and a
 raised serological markers of inflammation

 -  Have problematic symptoms associated with established diverticular disease, post a
 diverticulitis episode

 -  Aged over 20 years

 -  Are on no treatment or have been on stabile medication for at least 6 weeks for
 diverticular disease

 -  Willing and able to provide a written informed consent.

 Exclusion Criteria:

 -  Aged less than 20 years

 -  Severe disease (ongoing severe active diverticulitis) as defined by hemoglobin < 8.0
 g/dl, white blood cell count, >20,000 cells/mm3, temperature >38.5°C, serum albumin <
 25 g/dl

 -  Surgical diverticular complications such as rectovaginal or bladder fistula, abscess,
 etc.

 -  Severe respiratory, cardiovascular, neurological, psychiatric, rheumatological, other
 gastrointestinal, etc. diseases

 -  Undergone major intestinal resections

 -  Patients with malignancy

 -  On NSAIDs

 -  Pregnancy or actively seeking pregnancy

 -  History of intolerance or allergy to probiotics

 -  Current drug or alcohol dependence syndrome

 -  Patients unable to consent for themselves

 -  Patients with severe learning difficulties