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 |
| Secondary identifying numbers | NKBBN/405/2017 |
- 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
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
Scientific
26/B/6 Buraczana Street
Gdynia
81-587
Poland
 ORCID ID |
0000-0002-2434-3599 |
|---|---|
| Phone | +48 509485357 |
| jaszefel@mp.pl |
Public
1 Powstania Styczniowego Street
Gdynia
81-519
Poland
| ORCID ID |
0000-0002-5929-5232 |
|---|---|
| Phone | +48 587260250 |
| wieslaw.kruszewski@gumed.edu.pl |
Study information
| Study design | Single-centre prospective interventional randomized double-blind study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| 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 | 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 |
| Secondary outcome measures | 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 |
| Overall study start date | 09/10/2017 |
| Completion date | 21/06/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 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
Gdynia Oncology Centre
1 Powstania Styczniowego Street
Gdynia
81-519
Poland
Faculty of Health Sciences
9b Powstania Styczniowego Street
Gdynia
81-519
Poland
Gdansk
80-211
Poland
7 Debinki Street
Gdansk
80-211
Poland
238A Aleja Grunwaldzka
Gdansk
80-266
Poland
Sponsor information
University/education
3a M. Skłodowskiej-Curie Street
Gdańsk
80-210
Poland
| Phone | +48 583491813 |
|---|---|
| zpo@gumed.edu.pl | |
| Website | http://mug.edu.pl/ |
"ROR" |
https://ror.org/019sbgd69 |
Funders
Funder type
University/education
Government organisation / Local government
- Alternative name(s)
- Medical University of Gdańsk, MUG
- Location
- Poland
Results and Publications
| Intention to publish date | 01/05/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| 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? |
|---|---|---|---|---|---|
| Participant information sheet | 04/05/2021 | No | Yes | ||
| Results article | 04/01/2022 | 12/01/2022 | Yes | No |
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.
