Effect of the Nutraceutical "MICODIGEST 2.0" on the Complications After Surgery for Colorectal Cancer

Double-blind Randomized Clinical Trial to Evaluate the Effect of the Nutraceutical "MICODIGEST 2.0" on the Complications After Surgery With Curative Intent for Colorectal Cancer

Most of Colorectal cancer (CRC) diagnosed are candidates for surgical resection with curative intent, although colorectal surgery is associated with some complications that could be life-threatening. Antibiotic prophylaxis is commonly used prior to the admission for the prevention of postoperative complications. However, this intervention can change the composition of intestinal microbiota and promote adverse inflammatory outcomes in CRC patients after surgery.

It seems the combination of different fungal extracts could be beneficial because of their role in gut microbiota modulation and their anti-inflammatory activity. Therefore, the fungal extract nutraceutical MICODIGEST 2.0 could be used to reduced the complications after CRC surgery.

Based on this hypothesis, we have designed a double-bind randomized clinical trial to evaluate the effect of MICODIGEST 2.0 on the complications after surgery with curative intent for CRC.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Surgery--Complications
• Intervention / Treatment: Dietary supplement: MICODIGEST 2.0 supplement; Dietary supplement: Placebo supplement

Detailed Description

Colorectal cancer (CRC) is one of the most common malignancies in western countries. Most of the CRC diagnosed are candidates for surgical resection with curative intent. Cure rates after surgery vary between 92 % and 67 % depending on the tumor stage. However, colorectal surgery is associated with some complications that could be life-threatening.

Antibiotic prophylaxis is commonly used prior to the admission for the prevention of this postoperative complications. Several studies have shown that antibiotic administration reduces the risk of infections associated with surgery. Nevertheless, this intervention does not modify the mortality and severity of other complications detected. Further, antibiotic prophylaxis could change the intestinal microbiota and promote adverse inflammatory outcomes in CRC patients after surgery.

Fungal polysaccharides have attracted attention because of their role in gut microbiota modulation. It seems that this type of polysaccharides could reduce pathogen levels and stimulate the growth of beneficial microorganism. Anti-inflammatory activity has also been described for these fungal polysaccharides. It seems the combination of different fungal extracts would send multiple stimuli to the immune system increasing intracellular reactions and interactions. Thus, the fungal extract nutraceutical MICODIGEST 2.0 could be used to reduced the complications after CRC surgery. MICODIGEST 2.0 is available since 2016 without any adverse effect reported.

For all these reasons we have designed a double-bind randomized clinical trial to evaluate the effect of MICODEGIST 2.0 on the complications after surgery with curative intent for CRC.

Apart from this purpose, we have also set the following secondary objectives:

• To evaluate the safety of MICODIGEST 2.0 in CRC patients.
• To evaluate the effect of MICODIGEST 2.0 on feal microbiome composition and diversity.
• To evaluate the effect of MICODIGEST 2.0 on inflammatory pattern, dietary pattern and quality of life.
• To analyze the effect of microbiome, inflammatory and dietary pattern on complications after surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joaquín Cubiella, MD PhD; Phone Number: 0034988385824; Email: joaquin.cubiella.fernandez@sergas.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. CRC patients who are candidates for surgical treatment with curative intent (risk I-III).
2. American Society of Anesthesiologists' Physical Status Classification (ASA) <3.
3. Patients aged between 18 and 85 years.
4. Eastern Cooperative Oncology Group (ECOG) scale between 0-2.
5. Patients with preserved cognitive function.
6. Patient's authorization after reading the study information sheet.

Exclusion Criteria:

1. Candidates for neoadjuvant therapy.
2. Patients with concomitant carcinoma.
3. Allergy to the supplied nutraceutical or presence of malabsorption syndrome.
4. Presence of mental disorders
5. Patient with active infection or antibiotic therapy in the last month.
6. Previous colorectal surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MICODIGEST 2.0 supplement; Treatment with MICODIGEST 2.0 will initiate with 10mL/day (before breakfast or before lunch) for 7 days, and rise to 20mL/day (10mL before breakfast and 10 mL before dinner) for 4-6 weeks.	Dietary supplement: MICODIGEST 2.0 supplement; MICODIGEST is a nutraceutical which contains 9 different fungal extracts: Ganoderma lucidum, Agaricus blazei, Grifola frondosa, Hericium erinaceus, Cordyceps sinensis, Inonotus obliquus, Pleurotus ostreatus, Polyporus umbellatus y Lentinula edodes
Placebo Comparator: Placebo; Treatment with placebo will initiate with 10mL/day (before breakfast or before lunch) for 7 days, and rise to 20 mL/day (before breakfast and before dinner) for 4-6 weeks.	Dietary supplement: Placebo supplement; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complications.	Anastomotic failure, infection, prolonged ileus, systemic complications and other will be measured. Clavien-Dindo classification will be used for grading the severity of these postoperative complications. These analysis will be measured to evaluate the effect of MICODEGIST 2.0 on the complications after surgery with curative intent for CRC.	week 4-6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse effects.	Adverse effects will be considered during follow-up and after surgery using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. This analysis will be measured to evaluate the safety of MICODIGEST 2.0 in CRC patients.	week 1-6
Fecal microbiome composition.	High-quality DNA extraction will be performed in fecal samples. The bacterial 16S ribosomal ribonucleic acid gene will be sequencing on an Illumina MiSeq. Metagenomic species and a database with >200.000 strains will be used to define the microbiome composition. This analysis will be used to evaluate the effect of MICODIGEST 2.0 on feal microbiome composition.	week 4-6
Neutrophil/Lymphocyte ratio.	Neutrophil/Lymphocyte will be measured dividing the absolute number of neutrophils by the absolute number of lymphocytes from peripheral blood sample. This inflammatory biomarker will be used to evaluate the effect of MICODIGEST 2.0 on inflammatory pattern.	week 4-6
C reactive protein (CRP) level.	CRP levels (mg/dL) from peripheral blood samples will be measured to evaluate the effect of MICODIGEST 2.0 on inflammatory pattern.	week 4-6
Tumor Necrosis Factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels.	TNF-apha (pg/mL) and IL-6 (pg/mL) from peripheral blood samples will be measured to evaluate the effect of MICODIGEST 2.0 on inflammatory pattern.	week 4-6
Dietary pattern assessment.	Patient-Generated Subjective Global Assessment survey (PG-SGA) will be used to assess the nutritional status. At the end of this survey, the patient will be rated nutritionally in one of three categories: "Well-nourished or anabolic" (PG-SGA - A), "Moderately or suspected of being undernourished" (PG-SGA B) and "Severely undernourished" (PG-SGA C). This analysis will be performed to evaluate the effect of MICODIGEST 2.0 on dietary pattern.	week 4-6
Quality of life assessment.	The 36-item Short Form Health Survey (SF-36) will be used to measure the health-related quality-of-life. The SF-36 is a 36-item patient-reported questionnaire that covers eight health domains. Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state. This analysis will be perfomed to evaluate the effect of MICODIGEST 2.0 on quality of life.	week 4-6

Collaborators and Investigators

• Sponsor: Fundacin Biomedica Galicia Sur

Publications and helpful links

General Publications

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• Gutierrez-Stampa MA, Aguilar V, Sarasqueta C, Cubiella J, Portillo I, Bujanda L. Impact of the faecal immunochemical test on colorectal cancer survival. BMC Cancer. 2020 Jul 1;20(1):616. doi: 10.1186/s12885-020-07074-y.
• Gutierrez-Stampa MA, Aguilar V, Sarasqueta C, Cubiella J, Portillo I, Bujanda L. Colorectal Cancer Survival in 50- to 69-Year-Olds after Introducing the Faecal Immunochemical Test. Cancers (Basel). 2020 Aug 25;12(9):2412. doi: 10.3390/cancers12092412.
• Cubiella J, Gonzalez A, Almazan R, Rodriguez-Camacho E, Fontenla Rodiles J, Dominguez Ferreiro C, Tejido Sandoval C, Sanchez Gomez C, de Vicente Bielza N, Lorenzo IP, Zubizarreta R. pT1 Colorectal Cancer Detected in a Colorectal Cancer Mass Screening Program: Treatment and Factors Associated with Residual and Extraluminal Disease. Cancers (Basel). 2020 Sep 6;12(9):2530. doi: 10.3390/cancers12092530.
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• Ralls MW, Miyasaka E, Teitelbaum DH. Intestinal microbial diversity and perioperative complications. JPEN J Parenter Enteral Nutr. 2014 Mar-Apr;38(3):392-9. doi: 10.1177/0148607113486482. Epub 2013 May 1.
• Ottosson F, Brunkwall L, Ericson U, Nilsson PM, Almgren P, Fernandez C, Melander O, Orho-Melander M. Connection Between BMI-Related Plasma Metabolite Profile and Gut Microbiota. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1491-1501. doi: 10.1210/jc.2017-02114.
• Liu CJ, Zhang YL, Shang Y, Wu B, Yang E, Luo YY, Li XR. Intestinal bacteria detected in cancer and adjacent tissue from patients with colorectal cancer. Oncol Lett. 2019 Jan;17(1):1115-1127. doi: 10.3892/ol.2018.9714. Epub 2018 Nov 15.
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Helpful Links

• World Health Organization. Cancer Today. International Agency for Research on Cancer. (2020)

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: March 23, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2021
• Last Update Submitted That Met QC Criteria: March 26, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Gut microbiota; Nutraceutical; Surgery Complications; Dietary pattern; Inflammatory pattern
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: COGOMELO 2.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No