Clinical trial NCT03742596: Effect of Probiotics Supplementation on the Side Effects of Radiation Therapy Among Colorectal Cancer Patients
Official title: Effect of Probiotics Supplementation on the Side Effects of Radiation Therapy on the Immune System Among Colorectal Cancer Patients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Colorectal Cancer
Keywords: Colorectal cancer
Radiotherapy
immune system
Inflammatory markers
Life quality
Lead sponsor: King Hussein Cancer Center
Sponsor class: OTHER
First posted: 2018-11-15
Enrollment: 0
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: The level of Immunoglobulin (Ig) A
timeFrame: Through study completion, an average of 1 year
measure: The level of Immunoglobulin (Ig) G
timeFrame: Through study completion, an average of 1 year
measure: The level of Immunoglobulin (Ig) M
timeFrame: Through study completion, an average of 1 year
measure: The Level of Interleukin (IL)-6
timeFrame: Through study completion, an average of 1 year
measure: The Level of Interleukin (IL)-1
timeFrame: Through study completion, an average of 1 year
measure: The Level of Interleukin (IL)-10
timeFrame: Through study completion, an average of 1 year
measure: The Level of Tumor Necrosis Factor (TNF)-α
timeFrame: Through study completion, an average of 1 year
measure: The Level of C-reactive protein (CRP)
timeFrame: Through study completion, an average of 1 yea
Secondary outcomes:
measure: Quality of Life of patients
timeFrame: Through study completion, an average of 1 year
measure: The gastrointestinal toxicity
timeFrame: Through study completion, an average of 1 year
Other outcomes:
measure: The level of White blood cell count (WBC)
timeFrame: Through study completion, an average of 1 yea
measure: The level of red blood cell count (RBC)
timeFrame: Through study completion, an average of 1 yea
measure: The mean corpuscular volume (MCV)
timeFrame: Through study completion, an average of 1 yea
measure: The mean corpuscular hemoglobin (MCH)
timeFrame: Through study completion, an average of 1 yea
measure: The mean corpuscular hemoglobin concentration (MCHC)
timeFrame: Through study completion, an average of 1 yea
measure: The Platelet count
timeFrame: Through study completion, an average of 1 yea
measure: The of Hemoglobin
timeFrame: Through study completion, an average of 1 yea
measure: The mean platelet volume (MPV)
timeFrame: Through study completion, an average of 1 yea
measure: The level of lymphocytes
timeFrame: Through study completion, an average of 1 yea
measure: The level of Monocytes
timeFrame: Through study completion, an average of 1 yea
measure: The level of eosinophils
timeFrame: Through study completion, an average of 1 yea
measure: The level of basophils
timeFrame: Through study completion, an average of 1 yea
measure: The level of neutrophils
timeFrame: Through study completion, an average of 1 yea
Locations:
city: Amman
country: Jordan
facility: King Hussein Cancer Center
Study officials:
affiliation: King Hussein Cancer Center
name: Fawzi Abuhijla, MD,MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Jordan
name: Lana M Agraib, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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).
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.