Lactobacillus Rhamnosus GG (ATCC 53103) in Mild-moderately Active UC Patients
Condition: Ulcerative Colitis Chronic Mild; Ulcerative Colitis Chronic Moderate
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study is a randomized double-blind clinical trial that intends to evaluate the efficacy
      and safety of LGG administration at two different doses, for 1 month, in ulcerative colitis
      (UC) patients with mild-moderate disease activity in therapy with oral mesalamine. Efficacy
      of therapy will be evaluated by clinical (Clinical Mayo score, quality of life assessment),
      endoscopic (Endoscopic Mayo score), histological, biochemical (white cell count, C-reactive
      protein), and molecular (mucosal colonization of the bacteria, pro- and anti-inflammatory
      cytokines measurement) parameters. UC patients with mild-moderately active disease despite
      oral treatment with mesalamine will be assessed at baseline for clinical, endoscopic,
      histologic inflammatory activity. After a wash-out period of 4 weeks of mesalamine, patients
      will be randomized to assume a regular (LGG 1.2 × 10^10 Colony Forming Units (CFU)/day, 2
      capsules a day) or a double (LGG 2.4 × 10^10 CFU/day, 4 capsules a day) dose of LGG for 1
      month. At the end of the treatment, clinical, endoscopic, and histologic inflammatory
      activity will be evaluated and compared to pre-treatment data. Adhesion and molecular effect
      of LGG will be also evaluated. Safety will be assessed by weekly phone calls and with direct
      physical examination at the end of the study period.
    

Detailed description: 
      Probiotic bacteria have been proposed as therapeutic option in several pathologic conditions,
      but their utilization is often not evidence-based driven. In inflammatory bowel disease
      (IBD), consistent heterogenity exists among published clinical studies. Aim of the present
      clinical study is to evaluate the effect of Lactobacillus rhamnosus GG (LGG), the probiotic
      bacteria most extensively investigated, with solid safety data and proven anti-inflammatory
      effect in experimental models, in ulcerative colitis (UC) patients, with a rigorous
      methodology, a well defined protocol, and with relevant outcomes clearly set.

      This study is a randomized double-blind clinical trial that intends to evaluate the efficacy
      and safety of LGG administration at two different doses, for 1 month, in UC patients with
      mild-moderate disease activity in therapy with oral mesalamine.The eligible patients will be
      identified by a screening visit (T-1), with consideration of inclusion and exclusion
      criteria, and informed consent will be signed. Then the patients will have a 4 weeks wash-out
      period, when oral mesalamine will be suspended, and biochemical tests [total blood count,
      C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum protein
      electrophoresis], and endoscopic examination with biopsies will be performed. The patients
      will be then evaluated again prior to the randomization to regular or double dose group (T0),
      and clinical activity and quality of life will be assessed. Patients will be randomized to
      assume a regular (LGG 1.2 × 10^10 CFU/day, 2 capsules a day) or a double (LGG 2.4 × 10^10
      CFU/day, 4 capsules a day) dose of LGG for 1 month. After 4 weeks of treatment, patients will
      be re-evaluated (T1), with physical examination and interview, and rectum-sigmoidoscopy with
      biopsies will be performed. The patients will then be allowed to assume the therapy they were
      taking at T-1 visit (mesalamine), and will be assessed for the last time after 4 weeks after
      treatment completition (T2), with physical examination and interview. Efficacy of therapy
      will be evaluated by comparison of clinical, endoscopic, histological, biochemical and
      molecular data, pre- and post-treatment (T1 vs. T0). Randomization of patients in the groups
      will be performed by a computer-generated randomization list, in a double blind fashion.
      Clinical activity will be evaluated by Clinical Mayo Score calculation. Quality of life will
      be evaluated by specific validated tests. Endoscopic activity will be evaluated by Endoscopic
      Mayo Score calculation, by an endoscopist blinded to clinical data of patients. Histologic
      activity will be evaluated by expert anatomopathologists, by means of Geboes score. Molecular
      activity of LGG will be evaluated by assessment of bacteria adhesion to the colonic mucosa,
      measured by real-time(RT)-Polymerase Chain Reaction (PCR) with specific primers on total DNA
      extracted by bioptic samples (as already described), and by quantification of expression of
      pro- and anti-inflammatory cytokines, before and after probiotic treatment, by means of
      RT-PCR on total RNA extracted from bioptic samples (as already described).

      Safety of LGG treatment will be assessed by weekly phone calls to the patients, in order to
      investigate the unexpected occurence of side-effects, and with direct physical examination
      and biochemical tests at the end of the study period (T1). Possible LGG translocation will be
      evaluated by RT-PCR with specific primers on total DNA extracted from peripheral blood
      collected from patients at the end of treatment (T1).
    

Intervention name(s): Lactobacillus rhamnosus GG ATCC 53103
Intervention type(s): Dietary Supplement
Intervention description(s): probiotic administration at two different doses for 1 month
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: probiotic; Lactobacillus rhamnosus GG; ATCC 53103; cytokines; adhesion