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A placebo-controlled comparative study on doses and the efficacy of Lentinula Edodes Mycelia (L.E.M.) for peripheral neuropathy remaining after chemotherapy with OxaliplatiN for colorectal cancer: LEMON trial (A placebo-controlled comparative study on doses and the efficacy of Lentinula Edodes Mycelia (L.E.M.) for peripheral neuropathy remaining after chemotherapy with OxaliplatiN for colorectal cancer)

LEMON trial

45

In patients aged 20 years and older with peripheral neuropathy lasting more than three months after oxaliplatin-based chemotherapy for colorectal cancer, the following allocation was made for the intervention. Total: 45 cases (29 males, 16 females) with an average age of 65.7 years Placebo group: 15 cases (10 males, 5 females) with an average age of 63.7 years Low-dose group: 15 cases (10 males, 5 females) with an average age of 65.5 years High-dose group: 15 cases (9 males, 6 females) with an average age of 67.9 years

Written informed consent was obtained, and 45 study participants deemed eligible by the principal investigator were assigned to three groups: placebo group, low-dose group, and high-dose group, ensuring no intergroup differences in allocation factors such as age and numbness. The subjects consumed the assigned test food for 12 weeks and visited the clinic every 4 weeks to assess numbness and pain using the Visual Analog Scale (VAS).

Two cases exhibited anticipated conditions. One case developed moderate skin itching (Grade 2) suspected to be shiitake dermatitis, while the other experienced mild stomach discomfort (Grade 1) with loss of appetite and indigestion. Both were known transient side effects of shiitake, and while the consumption of the test food was continued, the symptoms resolved by the end of the study.

To evaluate the efficacy and dose of L.E.M., three groups were compared: low dose (600 mg/day), high dose (1800 mg/day) L.E.M., and placebo. The primary endpoint was the change in CIPN numbness intensity index (VAS score) between the placebo and low-dose groups at 12 weeks (compared and evaluated between groups using two-tailed unpaired t-test). As a result, there was no significant difference between the placebo and low dose groups in the reduction of VAS numbness scores at 12 weeks (placebo - 12.2 [95% confidence interval {CI}; -34.5 to 10.1] vs low dose -10.7 [95% CI; -27.1 to 5.7], p= .83). However, although not significant, there was a clinically beneficial change in the VAS numbness score in the high-dose group versus the placebo group (placebo -12.2 vs high-dose - 29.3 [95% CI; -53.4 to -5.2], p = 0.06), the secondary endpoint. Similarly, An6 ("difficulty walking") scores on the FACT-GOG/NTX questionnaire at 12 weeks improved in the highdose group (placebo -0.1 [95% CI; -1.2 to 1.0], low dose -0.4 [95% CI; -1.6 to 0.8] and highdose -1.0 [95% CI; -2.0 to 0.0]).

High dose (1800 mg/day) L.E.M. administration shows potential to improve oxaliplatin-induced CIPN in patients with colorectal cancer.

Nov. 30, 2024

No

There are no plans to share data that has been processed to prevent the identification of individual subjects.

https://jrct.mhlw.go.jp/latest-detail/jRCTs051210085

Kawakami Hisato

Kindai University Hospital

337-2,Ohno-higashi, Osaka-Sayama City, Osaka

kawakami_h@med.kindai.ac.jp

Kawakami Hisato

Kindai University Hospital

337-2,Ohno-higashi, Osaka-Sayama City, Osaka

+81-72-366-0221

kawakami_h@med.kindai.ac.jp

Complete

Sept. 16, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. Patients with residual peripheral neuropathy for 3 months after oxaliplatin completion
2. It is diagnosed as adenocarcinoma (including mucinous cancer, signet ring cell carcinoma, and medullary carcinoma) in the 8th edition of the Colorectal Cancer Handling Regulations by histopathological diagnosis..
3. The main occupied site by surgical and excised specimens is diagnosed from the cecum to the lower rectum (C, A, T, D, S, RS, Ra, Rb, P) in the 8th edition of the Colorectal Cancer Handling Regulations.
4. At the time of completion of surgery, residual cancer is considered to be R0 or R1.
5. No synchronous colorectal cancer
6. Patients diagnosed with Grade 1 or higher sensory CIPN based on the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v. 4.0 grading scale
7. At the time of enrollment, patients with more than 40mm of the numbness VAS due to oxaliplatin-induced peripheral neuropathy.
8. 20 years old or older
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
10. Vital organ functions are preserved
11. Possible to take foods and drugs orally
12. Patients who can write with their dominant hand. Writing by a substitute is not allowed.
Written informed consent from patient.
13. Patient has been informed of the study and agrees to its provisions and has provided written informed consent

1. Patients with peripheral neuropathy other than CIPN, such as fibromyalgia and diabetic peripheral neuropathy.
2. Cases in which the drug dose to CIPN that has already been performed within 2 weeks before randomization is not stable*. *Patients who have an increase or decrease of 10% or more of the daily dose of the drug used.
3. Patients with serious complications (ileus, intestinal obstruction, interstitial pneumonia or pulmonary fibrosis, uncontrolled diabetes, heart failure, renal failure, liver failure, etc.)
4. Patients with a severe complication Patients who have allergy to L.E.M. or similar chemical agents
5. Patients receiving gabapentin
6. Pregnant or lactating women and those who may or will become pregnant
7. Patients who participate in other clinical trials
8. Patient who is judged inappropriate to participate in this study by the principle investigator.

Both

chemotherapy-induced peripheral neuropathy

Oral ingestion of test tablets with L.E.M. or placebo (12 grains per a day; 12 weeks)

CIPN

-

039

-

Evaluate the change in CIPN VAS (numbness) from start to the end of the initial treatment period (weeks 0-12) in the placebo and low-dose groups

1. Evaluate the change in CIPN VAS (pain) from start to the end of the initial treatment period (weeks 0-12) in the placebo and low-dose groups
2. Evaluate the change in CIPN VAS (numbness, pain) from start to the end of the initial treatment period (weeks 0-12) in the placebo and high-dose groups.
3. Evaluate the change in CIPN VAS (numbness, pain) from start to 4 and 8 weeks.
4. Peripheral sensory neuropathy grade(CTCAE Ver.4) every 4 weeks from the start of administration.
5. QOL survey using FACT-GOG / NTX every 4 weeks from the start of administration
6. Score of adverse events(CTCAE Ver.4)
7. Statistically estimate the dose-response relationship by sigmoid function, linear regression, etc.

+81-744-29-8835

July. 21, 2021

none