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

Sponsor

Fundacin Biomedica Galicia Sur (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04821258

Collaborator

(none)

144

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Surgery--Complications	Dietary Supplement: MICODIGEST 2.0 supplement Dietary Supplement: Placebo supplement	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

CRC candidates for surgery with curative intent will be considered to include in the study. Patients who fulfill criteria will be screened and randomly allocated to be treated with MICODIGEST 2.0 or placebo previous to the admission. Patients will be also stratified based on tumor location (distal or proximal to splenic flexure). Patients will be followed for 4-6 weeks until surgery intervention.CRC candidates for surgery with curative intent will be considered to include in the study. Patients who fulfill criteria will be screened and randomly allocated to be treated with MICODIGEST 2.0 or placebo previous to the admission. Patients will be also stratified based on tumor location (distal or proximal to splenic flexure). Patients will be followed for 4-6 weeks until surgery intervention.

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2021

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Rate of complications. [week 4-6]
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.

Secondary Outcome Measures

Frequency of adverse effects. [week 1-6]
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.
Fecal microbiome composition. [week 4-6]
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.
Neutrophil/Lymphocyte ratio. [week 4-6]
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.
C reactive protein (CRP) level. [week 4-6]
CRP levels (mg/dL) from peripheral blood samples will be measured to evaluate the effect of MICODIGEST 2.0 on inflammatory pattern.
Tumor Necrosis Factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels. [week 4-6]
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.
Dietary pattern assessment. [week 4-6]
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.
Quality of life assessment. [week 4-6]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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