Completed

NCT Number: NCT01402648

Estrogen Receptor Beta Agonists (Eviendep) and Polyp Recurrence

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Adenocarcinoma of Colon Recurrent

Age range

50 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Ospedale Policlinico Consorziale - Gastroenterology Unit

Bari, 70124, Italy

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

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.

Maltodextrins

Dietary Supplement

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

Primary outcomes

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

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

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.

Secondary outcomes

Safety assessed by unchanged hematochemistry

Time frame: 30 and 60 days following dietary oral supplementation

Hemoglobin ≥ 12.0 g/dL; platelets ≥ 120,000/mm3; INR ≤ 1.5; AST or ALT ≤ 1.5 times the upper limit of normal values (ULN); Alkaline Phosphatase ≤ 1.5 times ULN; Bilirubin ≤ 1.5 times ULN; BUN ≤ 40 mg/dL; normal blood pressure or controlled hypertension
Urinary lignans

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

To verify comparability of phytoestrogens contributed from the common diet in the two arms at baseline, and to assess compliance to the active comparator during the study period.

Sponsors and collaborators

Lead sponsor

CM&D Pharma Limited

Industry

Registry information

Official study title

Effects of the Dietary Supplementation With a Blend of ER Beta Agonists on the Expression of ER Beta and Related Biomarkers of Cell Proliferation and Apoptosis, in Sporadic Colon Adenopolyposis

Acronym: CRC

Important dates

Study start: 2009
Primary completion: 2011
Study completion: 2011
First posted: Jul 26, 2011
Registry last updated: Jul 26, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.