The effect of supplementation with an amino acid that helps the body build protein (L-arginine) on change in the immune system of colorectal cancer patients

ISRCTN	ISRCTN61139514
DOI	https://doi.org/10.1186/ISRCTN61139514
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	NKBBN/405/2017
Sponsor	Gdańsk Medical University
Funder	Gdański Uniwersytet Medyczny

Submission date: 31/03/2021
Registration date: 19/04/2021
Last edited: 26/09/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Colorectal cancer is cancer that occurs in the colon or rectum. Sometimes it is called colon cancer, for short. As the drawing shows, the colon is the large intestine or large bowel. The rectum is the passageway that connects the colon to the anus.
L-arginine (L-arg) is an amino acid that helps the body build protein. Your body usually makes all the L-arginine it needs. L-arginine is also found in most protein-rich foods, including fish, red meat, poultry, soy, whole grains, beans and dairy products.
L-arg supplementation may improve treatment outcomes from tumours by altering the activity of the immune system.

Who can participate?
Adult patients with diagnosed colorectal cancer qualified to undergo radical surgical treatment

What does the study involve?
Participants will be randomly allocated to receive either L-arg or placebo for 9 days prior to surgery.

What are the possible benefits and risks of participating?
Benefits: Currently, there is insufficient evidence and long-term follow-up to conclusively conclude that L-arginine supplementation improves the outcome treatment in colorectal cancer patients. The aim of our study is to explore this possibility. Thus, an improvement in their health cannot be guaranteed. However, the participation of patients in the study and its results may in the future contribute to improving the results of oncological treatment of other colorectal cancer patients.
Risks: Very rarely, abdominal pain, nausea or diarrhoea may occur after high doses of L-arginine exceeding 30 g per day. These symptoms disappear after withdrawal L-arginine or reducing its doses. We plan to supplement with 10 g of L-arginine daily.

Where is the study run from?
Medical University of Gdańsk, MUG (Poland)

When is the study starting and how long is it expected to run for?
October 2017 to June 2020

Who is funding the study?
Medical University of Gdańsk, MUG (Poland)

Who is the main contact?
Dr Jarosław Szefel, jaszefel@mp.pl
Prof Wiesław Kruszewski, wieslaw.kruszewski@gumed.edu.pl

Contact information

Dr Jarosław Szefel
Scientific

26/B/6 Buraczana Street
Gdynia
81-587
Poland

ORCID ID	0000-0002-2434-3599
Phone	+48 509485357
Email	jaszefel@mp.pl

Prof Wiesław Kruszewski
Public

1 Powstania Styczniowego Street
Gdynia
81-519
Poland

ORCID ID	0000-0002-5929-5232
Phone	+48 587260250
Email	wieslaw.kruszewski@gumed.edu.pl

Study information

Primary study design	Interventional
Study design	Single-centre prospective interventional randomized double-blind study
Secondary study design	Randomised controlled trial
Participant information sheet	ISRCTN61139514_PIS.docx
Scientific title	The effect of L-arginine supplementation and surgical trauma on the frequency myeloid-derived suppressor cells and T lymphocytes in tumour and blood of colorectal cancer patients.
Study acronym	L-ArgRectCanc
Study objectives	L-arginine (L-arg) supplementation improves treatment outcomes for non-auxotrophic tumours by altering the activity of the immune system.
Ethics approval(s)	Approved 09/10/2017, Independent Bioethics Committee for Scientific Research at Medical University of Gdańsk (Dębinki 7, 80-211, Gdańsk, Poland; +48 58 349 10 11; irmez@gumed.edu.pl), ref: NKBBN/405/2017
Health condition(s) or problem(s) studied	The effect of L-arg supplementation in patients undergoing surgery for colorectal cancer
Intervention	L-arginine and placebo kits are prepared and labelled with numbers randomly assigned by LLC Ethifarm (Poznan, Poland). Each kit contains 180 capsules of 0.5 g of substance. Patients are instructed to take 20 capsules (5 capsules 4 times a day) for 9 days immediately prior to surgery. Researchers and patients does not know what is inside the capsules, and this information is disclosed by LLC Ethifarm after the end of the study. Randomisation: L-arginine and placebo kits were prepared and labelled with numbers randomly assigned by LLC Ethifarm (Poznan, Poland). Information on the content of the kits was disclosed by LLC Ethifarm to our research team at the end of the trial.
Intervention type	Supplement
Primary outcome measure(s)	Measured : 1. L-arg and ASS1 concentration, and ASS1 mRNA expression in tumour, intestinal mucosa, and blood measured using flow cytometry, quantitive PCR and ELISA 2. The frequency of M-MDSC and PMN-MDSC in tumour, intestinal mucosa (A2, B2), and blood measured using flow cytometry
Key secondary outcome measure(s)	Blood parameters measured using flow cytometry and ELISA before supplementation; one day after the end of supplementation - immediately before the surgery; and one day after the surgery: 1. ASS1 concentration 2. The frequency of Th1 cells 3. The frequency of Th2 cells 4. The Th1/Th2 ratio 5. The frequency of Treg cells 6. The frequency of Th17 7. Th17/Treg ratio 8. CRP concentrations and its relation to the frequency of PMN-MDSC, M-MDSC and Th1, Th2 9. The frequency of PMN-MDSC in blood 10. The frequency of M-MDSC in blood
Completion date	21/06/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	100
Total final enrolment	65
Key inclusion criteria	Adult patients with diagnosed colorectal cancer qualified to undergo radical surgical treatment
Key exclusion criteria	1. Chemotherapy and/or radiotherapy in the last 5 years 2. Autoimmune diseases 3. Liver or kidney failure 4. Uncontrolled diabetes 5. Acute and chronic inflammatory diseases
Date of first enrolment	30/04/2018
Date of final enrolment	30/04/2020

Locations

Countries of recruitment

Poland

Study participating centres

Maritime Polish Red Cross Memorial Hospital

Department of Surgical Oncology
Gdynia Oncology Centre
1 Powstania Styczniowego Street
Gdynia
81-519
Poland

Medical University of Gdansk

Division of Oncological Propedeutics
Faculty of Health Sciences
9b Powstania Styczniowego Street
Gdynia
81-519
Poland

Medical University of Gdansk

Department of Clinical Nutrition
Gdansk
80-211
Poland

Medical University of Gdansk

Department of Histology
7 Debinki Street
Gdansk
80-211
Poland

WSB University in Gdansk

Faculty of Finance and Management
238A Aleja Grunwaldzka
Gdansk
80-266
Poland

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
IPD sharing plan	All data generated or analysed during this study will be included in the subsequent results publication.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		04/01/2022	12/01/2022	Yes	No
Participant information sheet			04/05/2021	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN61139514_PIS.docx: uploaded 04/05/2021

Editorial Notes

12/01/2022: Publication reference added.
04/05/2021: The participant information sheet was uploaded as an additional file.
20/04/2021: Internal review.
19/04/2021: Trial's existence confirmed by Independent Bioethics Committee for Scientific Research at Medical University of Gdańsk.