Clinical trial NCT02115867: Effect of a Probiotic on Diverticular Symptoms
Official title: Assessment of the Probiotic Symprove as a Dietary Supplement in Patients With Symptomatic Diverticular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diverticular Disease
Keywords: diverticular disease
diverticulitis
diverticulosis
Lead sponsor: King's College Hospital NHS Trust
Sponsor class: OTHER
First posted: 2014-04-16
Enrollment: 143
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in symptoms assessment score
timeFrame: 90 days
Secondary outcomes:
measure: Change in faecal microbiota
timeFrame: 90 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
affiliation: King's College Hospital NHS Trust
name: Ingvar Bjarnason, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College Hospital NHS Trust
name: Savvas Papagrigoriadis, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: