Estrogen Receptor Beta Agonists (Eviendep) and Polyp Recurrence
Condition: Adenocarcinoma of Colon Recurrent
MeSH terms: Adenocarcinoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The decreased Estrogen Receptor beta (ERβ) expression in the non adenomatous mucosa of
      ApcMin/+ mice favours intestinal neoproliferation. The dietary supplementation with a blend
      of ERβ agonists and lignin has been shown to recover ERβ to the healthy wild type levels, and
      a reduced polyp number and lower dysplasia was also observed in the adenomatous mucosa. In
      this randomised, double blind and placebo controlled study, we assessed if ERβ similarly
      guides the apoptotic control of cell proliferation in the non adenomatous colon mucosa of
      patients affected from sporadic adenopolyposis, prone to polyp recurrence. For 60 day in
      advance of the screening colonoscopy, patients were supplemented with a dietary blend of ERβ
      agonists and lignin (Eviendep, CM&D Pharma Limited, London, UK) on top their common diet
      (left unchanged during the study period), to study if the pro-proliferative behavior of the
      non adenomatous mucosa was effected. Sixty patients naïve from previous and concomitant
      hormonal or anti-inflammatory CRC chemoprevention were sequentially 1:1 randomised to active
      or placebo supplementation. ERα and ERβ (mRNA, Western Blotting, Elisa, immunostaining),
      TUNEL, caspase-3 and Ki-67 (immunostaining) were assessed in bioptic normal colon mucosa
      samples. Study power: 80%, type 1 error: .05 (two-tails). Statistics: Non parametric Wilcoxon
      test for efficacy. MANOVA for proliferative and apoptotic biomarkers relationships to the
      common diet and to the 60 day supplementation.
    

Detailed description: 
      Enrolled patients were actively ongoing the surveillance program for the follow up of polyp
      recurrence and progression to CRC. Eligible patients should have undergone a polypectomy
      since 2003, affected by multiple polyps < 10 mm or one-two adenomas < 10 mm and/or with a
      grade of dysplasia to make them classified at intermediate risk for CRC, and scheduled to
      screening colonoscopy each 3-5 years. Patients were sequentially 1:1 randomly allocated to
      placebo or Eviendep at baseline (T0). The dietary supplements were administered twice a day
      for 60 days in advance of the screening colonoscopy, thus covering approximately eight
      complete colon epithelial turnover to occur. Five days in advance of T60 colonoscopy,
      patients refrained from fresh and cooked fruit and vegetable intake. Bowel cleansing was
      achieved by PEG 4000 oral administration (1120 g/4 L water solution). N=8 biopsy
      samples/patient were collected from the non adenomatous mucosa in the sigmoidal colon. Small
      polyps (diameter less or equal 0.5 cm) were topically electrocoagulated, whereas villous and
      tubulovillous polyps (diameter equal or higher than 0.5 cm) were submitted to the
      histological assessment.
    

Intervention name(s): Eviendep (CM&D Pharma Limited, UK); Maltodextrins
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 175 mg milk thistle (fruit dry extract, 70% in silymarin)+ 20 mg flaxseed (dry extract, 40% in secoisolariciresinoldiglucoside)+750 mg non-starch, insoluble and indigestible fiber (6% in lignin). Provided in 5 g sachets, to be dissolved in half glass water, administered twice a day for 60 days on top of the common diet.; 900 mg maltodextrin+excipient as per the active comparator eviendep, up to 5 g/sachet
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Non adenomatous mucosa; Estrogen Receptor beta and apoptosis; Adenoma recurrence; Screening colonoscopy every 3-5 years; patients at intermediate risk for CRC