Mechanistic Randomized Controlled Trial (RCT) of Mesalazine in Symptomatic Diverticular Disease
Condition: Diverticulosis, Colonic
MeSH terms: Diverticular Diseases; Diverticulum; Diverticulosis, Colonic
Study type: Interventional

Summary: 
      Diverticulosis (bulges in the bowel wall) affects two third of the elderly population in the
      UK. Diverticular disease and its complications are responsible for 68000 hospital admissions
      and 2000 deaths per year. It commonly produces recurrent short lived abdominal pain, changes
      in bowel habit and incontinence. The causes of symptoms are not known and the treatments
      unsatisfactory. Recent studies have found an association between inflammation, alteration of
      bowel nerves and symptoms. Mesalazine is an anti-inflammatory drug used in inflammatory bowel
      conditions, such as ulcerative colitis and crohn's disease. We plan to perform a randomized
      double blind (neither the patients or the doctors known which treatment the patient is
      taking) placebo (sham medication) controlled trial of mesalazine in symptomatic diverticular
      disease patients. We anticipate a reduction in the amount of inflammation, bowel nerve
      changes and symptoms in patients taking mesalazine compare to those taking the placebo.
    

Detailed description: 
      Diverticular disease affects two thirds of the elderly population in the United Kingdom. Only
      a small fraction of individuals with diverticulosis develop symptoms, perhaps 1 in 10, for
      reasons which are not well understood. The symptoms however are quite disabling as we found
      in a recent survey which indicated that around 36% suffered recurrent abdominal pain.
      Surprisingly, given the severity of the disability there has been very little research into
      the factors predicting the development of painful diverticular disease. Recent studies have
      indicated however that there may be an inflammatory component since the best predictor of
      recurrent abdominal pain is a previous episode of acute diverticulitis.

      Just what initiates an attack of acute diverticulitis is poorly understood but may include
      the inspissation of fecal material in the diverticulum which then leads to pressure on the
      lining epithelium and a break down of barrier function. This allows colonic bacteria to enter
      the lamina propria where they cause acute inflammation, attracting pus cells from the
      circulating blood and creating micro-abscesses. The resolution of this involves fibrosis and
      scaring together with muscular hypertrophy which may well lead to secondary motor
      abnormalities. Patients with symptomatic diverticular disease are known to have higher
      intraluminal pressures, both at baseline and in response to stimuli such as a meal or
      prostigmine.

      A recent report in which patients admitted with acute diverticulitis were followed for two
      years found that a very high proportion of such individuals subsequently develop recurrent
      chronic abdominal pain. Recent work has indicated that this leaves a permanent change in
      mucosal innervation. Markers of nerve injury including galanin and substance P are
      upregulated in patients with symptoms as opposed to those without. This is the first time
      that an objective marker has been shown to distinguish patients on the basis of symptoms.

      While acute diverticulitis may be the initiating insult, a chronic low level inflammation may
      also be required to maintain visceral hypersensitivity. Where detailed quantitative histology
      has been performed in diverticular disease, some individuals have been identified with a
      lymphocytic infiltration. In other circumstances, chronic inflammation sensitises mucosal
      nerves and is associated with visceral hypersensitivity, something which has also been noted
      in symptomatic diverticular disease.

      Whether anti-inflammatory agents could reverse this process is as yet unknown but there are
      currently available safe and effective treatments for inflammatory bowel disease such as 5
      amino-salicylic acid or budesonide which might well be effective and allow further evaluation
      of the role of low grade inflammation in symptomatic diverticular disease.

      This study aims to investigate the inflammatory, neurological and symptomatic effects of
      mesalazine in diverticular disease.
    

Intervention name(s): Mesalazine; Placebo
Intervention type(s): Device; Drug
Intervention description(s): 3 grams daily for 3 months; 3 grams daily for 3 months
Other intervention name(s): Salofalk®; 5 ASA; Sham medication
Intervention MeSH terms: Mesalamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Diverticular disease; Inflammation; Mesalazine