Effect of Probiotics Supplementation on the Side Effects of Radiation Therapy Among Colorectal Cancer Patients

Effect of Probiotics Supplementation on the Side Effects of Radiation Therapy on the Immune System Among Colorectal Cancer Patients

Colorectal cancer (CRC) is one of the most common types of cancer worldwide in general and in Jordan in specific. The studies that investigate the role of Probiotics supplementation in improving the inflammatory response, gastrointestinal toxicity and life quality of patients with colorectal cancer during radiotherapy are limited. So, this study aimed to study the effect of probiotics on the response of inflammatory markers, gastrointestinal toxicity, and quality of life in patients with colorectal cancer during radiation therapy.

An interventional double-blind randomized clinical trial (RCT) design will be used in this study. Forty patients will be recruited and assigned either to receive 3 times a day probiotic supplement or to be control with no intervention. The demographic data, anthropometric measurements, Cancer Quality of Life Questionnaire and blood samples will be collected at baseline and at end of radiation therapy. Interleukin-6, interleukin-1,interleukin-10 IL-10, C-reactive protein, tumor necrosis factor-alpha and complete blood count (CBC) will be measured.

The results will approve or disapprove the beneficial effect of using probiotics as adjuvant therapy for CRC patients and other types of cancer to reduce the side effects of radiotherapy and raise body weight as well as improving their quality of life.

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer
• Intervention / Treatment: Dietary supplement: Probiotic Formula Capsule; Drug: Control

Detailed Description

To meet the objectives of the study, a control group will be included in parallel with the treatment group in this trail. Forty patients (aged 35-65 years) who recently diagnosed with CRC will be recruited conveniently from the radiation oncology clinic at the King Hussein Cancer Center (KHCC), Amman, Jordan. Patients who meet the inclusion criteria and agree to participate and to take the drug will be allocated to the probiotic supplementation group, while patients who agree to participate but not to receive the drug will be allocated to the control group. The duration of the intervention will be 5 weeks, from the day of radiation until the end of treatment.

For the participants, the King Hussein Cancer Center (KHCC) hospital setting will be utilized for data collection. The patients will be recruited over 12 months and all patients will be asked to sign a written informed consent before enrollment. The patients that will be assigned to the probiotics group (n=20), to receive 3 times a day probiotic supplement. The duration of the intervention (administration of probiotics) will start 10-14 days before radiotherapy and continue over the 5 weeks duration of treatment under the supervision of the treating physician and end with the end of radiation therapy. The blood sample will be collected at baseline and at the end of radiation therapy and 10-14 days after radiation therapy.

The demographic data of each subject will be collected such as; gender, age, body mass index (BMI), tumor location, malignant tumors stage, tumor differentiation, educational level, occupation, family history, smoking, dietary and physical activity. At baseline and end line of the radiation therapy, a Cancer Quality of Life Questionnaire C30 (QLQ-C30) will be collected and blood sample tests will be withdrawn and the following biochemical variables will be measured: immunoglobulin G, immunoglobulin M, immunoglobulin A, interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-1(IL-1), interleukin-10(IL-10), interleukin-12 (IL-12), Tumor necrosis factor-alpha (TNF-α) and complete blood count (CBC).

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Lana M Agraib, PhD; Phone Number: +692795152669; Email: lanamg2007@yahoo.com
• Study Contact Backup: Name: Fawzi Abuhijla, MD,MSc; Phone Number: +69277764888; Email: FHijle@khcc.jo

Study Locations

• Jordan
  • Amman, Jordan
    • King Hussein Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men or women,
2. Aged from 35- 65 years with histologically proven CRC and
3. Histologically proven CRC with stage I, II, III
4. Will exposed newly to radiotherapy with the absence of any psychological, sociological or geographical condition that potentially affects the compliance with the study protocol and follow-up schedule.

Exclusion Criteria:

1. Active infection treated by antibiotic therapy or recent infection or recent antibiotic use;
2. Severe cardiovascular and cerebrovascular diseases that could not tolerate radical surgery;
3. Recent use of probiotics, prebiotics, or synbiotic;
4. Evidence of immunodeficiency;
5. Cancer stage IV
6. Pregnancy,
7. Recent/concurrent admission to ER
8. Co-existence of other malignant neoplasms, no other type of cancer in the past 5 years, any serious concomitant systemic disorders or diseases incompatible with the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic Formula Capsule; In this intervention arm the patients will receive oral viable capsules of probiotic contain (1*10 10 colony forming unit (CFU)/g) of lactobacillus (Lactobacillus rhamnosus , Lactobacillus acidophilus , Lactobacillus reuteri, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus gasseri, Lactobacillus plantarum) and bifidobacteria (Bifidobacterium lactis, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium infantis) species three times a per day	Dietary supplement: Probiotic Formula Capsule; The Probiotic will be coded in a specific label by a researcher. The patient will receive 2 bottles of the drug every 2 weeks and will be followed weekly for 7 weeks.; Other Names: Treatment
Other: Control; In this intervention arm, the control arm will receive normal treatment without any probiotic	Drug: Control; The Placebos will be coded in a specific label by a researcher.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The level of Immunoglobulin (Ig) A	The level of Immunoglobulin (Ig) A in g/L at both baseline and end line of intervention	Through study completion, an average of 1 year
The level of Immunoglobulin (Ig) G	The level of Immunoglobulin (Ig) G in g/L at both baseline and end line of intervention	Through study completion, an average of 1 year
The level of Immunoglobulin (Ig) M	The level of Immunoglobulin (Ig) M in g/L at both baseline and end line of intervention	Through study completion, an average of 1 year
The Level of Interleukin (IL)-6	The Level of Interleukin (IL)-6 in pg/ml at both baseline and end line of intervention	Through study completion, an average of 1 year
The Level of Interleukin (IL)-1	The Level of Interleukin (IL)-1 in pg/ml at both baseline and end line of intervention	Through study completion, an average of 1 year
The Level of Interleukin (IL)-10	The Level of Interleukin (IL)-10 in pg/ml at both baseline and end line of intervention	Through study completion, an average of 1 year
The Level of Tumor Necrosis Factor (TNF)-α	The Level of TNF-α in pg/ml at both baseline and end line of intervention	Through study completion, an average of 1 year
The Level of C-reactive protein (CRP)	The Level of CRP in mg/ml at both baseline and end line of intervention	Through study completion, an average of 1 yea

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life of patients	The average score of the general quality of life (QoL) subscales assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ) which use five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting) range from"Not at A Quite Very" to "Very Much " , and a single global health status/QoL scale range from one (very poor) to 7(Excellent) . In addition, the questionnaire contains five symptom scales that are commonly reported by cancer patients (dyspnea, loss of appetite, insomnia, constipation, and diarrhea) and the perceived financial impact of the disease scale that range from"Not at A Quite Very" to "Very Much ".	Through study completion, an average of 1 year
The gastrointestinal toxicity	Number and percent of participants with treatment-related adverse events as assessed by NCI Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE) change from baseline in the occurrences and grad of Adverse Events on grading scale at 5 Weeks	Through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The level of White blood cell count (WBC)	he level of WBC as cells/ul at both baseline and end line of intervention	Through study completion, an average of 1 yea
The level of red blood cell count (RBC)	The level of RBC as cells/ul at both baseline and end line of intervention	Through study completion, an average of 1 yea
The mean corpuscular volume (MCV)	The MCV in fl at both baseline and end line of intervention	Through study completion, an average of 1 yea
The mean corpuscular hemoglobin (MCH)	The MCH in pg at both baseline and end line of intervention	Through study completion, an average of 1 yea
The mean corpuscular hemoglobin concentration (MCHC)	The MCH in g/dl at both baseline and end line of intervention	Through study completion, an average of 1 yea
The Platelet count	The Platelet count as cells/ ul at both baseline and end line of intervention	Through study completion, an average of 1 yea
The of Hemoglobin	The Hemoglobin in g/dl at both baseline and end line of intervention	Through study completion, an average of 1 yea
The mean platelet volume (MPV)	The MPV in fl at both baseline and end line of intervention	Through study completion, an average of 1 yea
The level of lymphocytes	The number of lymphocytes cells at both baseline and end line of intervention	Through study completion, an average of 1 yea
The level of Monocytes	The number of Monocytes cells at both baseline and end line of intervention	Through study completion, an average of 1 yea
The level of eosinophils	The number of eosinophils cells at both baseline and end line of intervention	Through study completion, an average of 1 yea
The level of basophils	The number of basophils cells at both baseline and end line of intervention	Through study completion, an average of 1 yea
The level of neutrophils	The number of neutrophils cells at both baseline and end line of intervention	Through study completion, an average of 1 yea

Collaborators and Investigators

• Sponsor: King Hussein Cancer Center

Publications and helpful links

General Publications

• Abayomi J, Kirwan J, Hackett A. The prevalence of chronic radiation enteritis following radiotherapy for cervical or endometrial cancer and its impact on quality of life. Eur J Oncol Nurs. 2009 Sep;13(4):262-7. doi: 10.1016/j.ejon.2009.02.007. Epub 2009 Jul 28.
• Abdollahi H. Probiotic-based protection of normal tissues during radiotherapy. Nutrition. 2014 Apr;30(4):495-6. doi: 10.1016/j.nut.2013.09.006. No abstract available.
• Abdollahi, H., Shiri, I., Atashzar, M., Sarebani, M., Moloudi, K., and Samadian, H. (2015), Radiation protection and secondary cancer prevention using biological radioprotectors in radiotherapy. International Journal of Cancer Therapy and Oncology, 3(3).
• Ambalam P, Raman M, Purama RK, Doble M. Probiotics, prebiotics and colorectal cancer prevention. Best Pract Res Clin Gastroenterol. 2016 Feb;30(1):119-31. doi: 10.1016/j.bpg.2016.02.009. Epub 2016 Feb 19.
• Bowen JM, Stringer AM, Gibson RJ, Yeoh AS, Hannam S, Keefe DM. VSL#3 probiotic treatment reduces chemotherapy-induced diarrhea and weight loss. Cancer Biol Ther. 2007 Sep;6(9):1449-54. doi: 10.4161/cbt.6.9.4622. Epub 2007 Jun 23.
• Ciernikova S, Mego M, Semanova M, Wachsmannova L, Adamcikova Z, Stevurkova V, Drgona L, Zajac V. Probiotic Survey in Cancer Patients Treated in the Outpatient Department in a Comprehensive Cancer Center. Integr Cancer Ther. 2017 Jun;16(2):188-195. doi: 10.1177/1534735416643828. Epub 2016 May 5.
• Ciorba MA, Hallemeier CL, Stenson WF, Parikh PJ. Probiotics to prevent gastrointestinal toxicity from cancer therapy: an interpretive review and call to action. Curr Opin Support Palliat Care. 2015 Jun;9(2):157-62. doi: 10.1097/SPC.0000000000000134.
• Dai C, Zheng CQ, Meng FJ, Zhou Z, Sang LX, Jiang M. VSL#3 probiotics exerts the anti-inflammatory activity via PI3k/Akt and NF-kappaB pathway in rat model of DSS-induced colitis. Mol Cell Biochem. 2013 Feb;374(1-2):1-11. doi: 10.1007/s11010-012-1488-3. Epub 2012 Oct 23.
• Dasari S, Kathera C, Janardhan A, Praveen Kumar A, Viswanath B. Surfacing role of probiotics in cancer prophylaxis and therapy: A systematic review. Clin Nutr. 2017 Dec;36(6):1465-1472. doi: 10.1016/j.clnu.2016.11.017. Epub 2016 Nov 24.
• Escamilla J, Lane MA, Maitin V. Cell-free supernatants from probiotic Lactobacillus casei and Lactobacillus rhamnosus GG decrease colon cancer cell invasion in vitro. Nutr Cancer. 2012 Aug;64(6):871-8. doi: 10.1080/01635581.2012.700758. Epub 2012 Jul 25.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2018
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: November 11, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 15, 2018

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Colorectal cancer; Radiotherapy; Inflammatory markers; immune system; Life quality
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 19 KHCC 111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The center (KHCC) where the study conducted emphasis of maintaining privacy and confidentiality of the participants' data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes