Effect of L-alanyl L-glutamine dipeptide on diarrhea, treatment response, and patients’ survival in colon cancer patients receiving chemotherapy
| ISRCTN | ISRCTN13489936 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13489936 |
| Secondary identifying numbers | 34918/3 |
- Submission date
- 03/03/2022
- Registration date
- 04/03/2022
- Last edited
- 08/04/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Signs and Symptoms
Plain English Summary
Background and study aims
Diarrhea caused by chemotherapy (chemotherapy-induced diarrhea) may represent a life-threatening side effect in cancer patients receiving chemotherapy. FOLFOX, an effective treatment for colon cancer, has been associated with diarrhea with high severity. Management of diarrhea is crucial to increase the survival of cancer patients and to improve the quality of life.
Glutamine is an abundant protein-peptide found in blood and may improve diarrhea symptoms.
This study aimed to provide evidence that L-alanyl L-glutamine dipeptide may have a positive influence on the incidence of diarrhea, treatment response, and the overall survival in colon cancer patients treated with modified FOLFOX-6 (mFOLFOX-6).
Who can participate?
Patients of both genders, aged ≥18 years with histologically confirmed colon adenocarcinoma; stages II, and III can participate in this study.
What does the study involve?
Patients who are treated with the standard mFOLFOX-6 therapy will be randomly allocated to receive glutamine dipeptide or not receive glutamine dipeptide.
What are the possible benefits and risks of participating?
The expected benefits include a decrease in the incidence of diarrhea together with improvement of the treatment response and the patients' survival compared to the placebo. There are no known risks of participation in this study.
Where is the study run from?
Tanta University (Egypt)
When is the study starting and how long is it expected to run for?
March 2019 to April 2023
Who is funding the study?
Taif University (Saudi Arabia)
Who is the main contact?
Dr Ahmed M. Kabel, ahmed.kabal@med.tanta.edu.eg
Contact information
Scientific
El-Geish street
Pharmacology Department
Faculty of Medicine
Tanta University
Tanta
31527
Egypt
 ORCID ID |
0000-0002-5101-8011 |
|---|---|
| Phone | +201123497411 |
| ahmed.kabal@med.tanta.edu.eg |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | The ameliorative potential of L-alanyl L-glutamine dipeptide in colon cancer patients receiving modified FOLFOX-6 regarding the incidence of diarrhea, the treatment response, and patients’ survival: a randomized controlled trial |
| Study hypothesis | Administration of L-alanyl L-glutamine dipeptide to colon cancer patients receiving modified FOLFOX-6 therapy can efficiently decrease the Incidence of diarrhea and improve the response to treatment and the patients’ survival |
| Ethics approval(s) | Approved 08/03/2019, Research Ethics Committee of Faculty of Medicine (Tanta University, El-Geish street, Tanta, Egypt, 31527; +201102344533; researchethicscommitteefomtu@gmail.com), ref: 34918/3 |
| Condition | Incidence of diarrhea in colon cancer patients receiving mFOLFOX-6 therapy |
| Intervention | Treatment Plan (Chemotherapy) All patients will be treated with the standard mFOLFOX-6 consisting of 2-hour intravenous (IV) infusion of oxaliplatin (85 mg/m²) on day 1, and 2-hour IV drip infusion of calcium folinate (400 mg/m²) on day 1, followed by IV injection of 5-FU (400 mg/m²) and continuous infusion of 5-FU (1200 mg/m²) on days 1-2 (Total 2400 mg/m² over 46-48 hours). The intravenous infusion will be continued every 2 weeks. Patients will be randomized to receive glutamine dipeptide or not receive glutamine dipeptide (control group). In the glutamine dipeptide group, (N(2)-L-Alanyl-L-Glutamine Dipeptide, (Dipeptiven), by Fresenius Laboratories, Germany) will be given IV in a dose of 20 gm/100ml on the day 1-2 regimen every 2 weeks. Follow up The included patients enrolled in both groups will be evaluated at the baseline (prior to chemotherapy) and after two, four, and six cycles of treatment. Treatment response to chemotherapy will be assessed every two cycles according to the Response Evaluation Criteria in Solid Tumors (RECIST). Treatment-related toxicities will be estimated according to standard World Health Organization (WHO) criteria. Diarrhea will be graded according to the National cancer institute. In case of diarrhea grades I and II, only supportive therapy will be considered. Grade III diarrhea will be managed with supportive therapy, IV fluids and hospitalization. Chemotherapy will be postponed till complete recovery and the dose of chemotherapy will be reduced. Regarding patients with grade IV diarrhea, they will be admitted to the ICU and given IV fluids, supportive care, monitoring of electrolytes and chemotherapy will be stopped until complete recovery with dose reduction in case of reinfusion. The randomization process will be carried out by flipping a coin. One side of the coin will denote the glutamate group and the other side will denote the placebo group. |
| Intervention type | Supplement |
| Primary outcome measure | At baseline (prior to chemotherapy) and after two, four, and six cycles of treatment: 1. Treatment response to chemotherapy will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 2. Diarrhea will be graded according to the National cancer institute. |
| Secondary outcome measures | Treatment-related toxicities will be estimated according to standard World Health Organization (WHO) criteria at the baseline and after two, four, and six cycles of treatment |
| Overall study start date | 01/03/2019 |
| Overall study end date | 01/04/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 100 |
| Total final enrolment | 44 |
| Participant inclusion criteria | 1. Patients of both genders 2. Aged ≥18 years 3. Have histologically confirmed colon adenocarcinoma stage II, and III according to American Joint Committee on Cancer and the Union for International Cancer Control (AJCC-UICC); 7th Edition 4. Have adequate hematological parameters (evidenced by white blood cell count ≥ 4000/μl and platelet count ≥ 100,000/μl). 5. Have adequate renal (creatinine < 1.5 mg/dl) and hepatic functions (serum total bilirubin < 1.5 mg/dl). |
| Participant exclusion criteria | 1. Patients with stage IV colon cancer. 2. Patients with second primary colon cancer. 3. Patients with colon cancer with any other co-morbidity. |
| Recruitment start date | 01/04/2022 |
| Recruitment end date | 01/08/2022 |
Locations
Countries of recruitment
- Egypt
Study participating centre
Faculty of Medicine
Clinical Oncology Department
Tanta
31527
Egypt
Sponsor information
University/education
Al-Haweiah
P.O. Box 888
Taif
21974
Saudi Arabia
| Phone | +966 12 727 2020 |
|---|---|
| dar@tu.edu.sa | |
| Website | http://www.tu.edu.sa/en/Pages/default.aspx |
"ROR" |
https://ror.org/014g1a453 |
Funders
Funder type
University/education
Government organisation / Local government
- Alternative name(s)
- TU
- Location
- Saudi Arabia
Results and Publications
| Intention to publish date | 01/05/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | We planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | Data used and/or analyzed during this study will not be available for public access because of patients' privacy but will be available from the corresponding author upon reasonable request (ahmed.kabal@med.tanta.edu.eg) |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 07/03/2022 | 08/04/2024 | Yes | No |
Editorial Notes
08/04/2024: Publication reference and total final enrolment added.
04/03/2022: Trial's existence confirmed by Taif University
