Estrogen Receptor Beta Agonists (Eviendep) and Polyp Recurrence

NCT01402648 | Completed Phase 1

• 1 other identifier: CMD-CRC09(2)
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adenocarcinoma of Colon Recurrent

Keywords

Non adenomatous mucosa; Estrogen Receptor beta and apoptosis; Adenoma recurrence; Screening colonoscopy every 3-5 years; patients at intermediate risk for CRC

Outcome Measures

Primary Outcomes (1)

• Expression of ERβ, ERα, TUNEL, Caspase-3, Ki-67 in bioptic samples of non adenomatous mucosa in sporadic adenopolyposis

  ERβ and ERα protein content (Elisa), mRNA and immunohistochemically stained cells (% over the total number of cells/field,ICH); TUNEL (%,ICH); caspase-3 (%,ICH), Ki-67 (%ICH), and comparison (mean, median, %ICH) between study groups. Safety assessed by no induction of ERα expression.

  60 days following dietary oral supplementation, in advance of the screening colonoscopy as per the planning of the surveillance program

Secondary Outcomes (2)

• Safety assessed by unchanged hematochemistry

  30 and 60 days following dietary oral supplementation

• Urinary lignans

  baseline (T0, 30 (T30) and 60 (T60) days during the study period

Study Arms (2)

Dietary supplement

PLACEBO COMPARATOR

900 mg Maltodextrins

Dietary Supplement: Maltodextrins

Eviendep (CM&D Pharma Limited, UK)

ACTIVE COMPARATOR

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).

Dietary Supplement: Eviendep (CM&D Pharma Limited, UK)

Interventions

Eviendep (CM&D Pharma Limited, UK) DIETARY_SUPPLEMENT

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.

Eviendep (CM&D Pharma Limited, UK)

Maltodextrins DIETARY_SUPPLEMENT

900 mg maltodextrin+excipient as per the active comparator eviendep, up to 5 g/sachet

Dietary supplement

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, age: 50-70 years
• Menopausal women since at least 2 years
• Diagnosed since 2003 for adenomas, underwent polypectomy and histological assessment
• Regularly inscribed and actively ongoing the surveillance program for the follow-up of adenoma recurrence and progression to advanced adenomas
• Screening colonoscopy every 3-5 years
• No previous or concomitant administration of ASA and NSAIDs
• No previous or concomitant administration of Hormonal Replacement Therapy (HRT)
• No previous or concomitant administration of other phytoestrogens

You may not qualify if:

• Chronic inflammatory intestinal disease
• Intestinal and/or extraintestinal malignant neoplasms
• Acute or chronic renal disease
• Anemia
• Coagulation disorders,
• BMI \> 30
• Systemic corticosteroids
• Anticoagulants or platelet antiaggregants
• Antibiotics within 30 days from enrollment

Sponsors & Collaborators

• CM&D Pharma Limited: lead

Study Sites (1)

Ospedale Policlinico Consorziale - Gastroenterology Unit

Bari, Bari, 70124, Italy

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 25, 2011
• First Posted: July 26, 2011
• Study Start: October 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: April 1, 2011
• Last Updated: July 26, 2011

Record last verified: 2011-07

Locations

IT (1)