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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Dietary Supplement: Probiotic Formula Capsule
* Drug: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women, Aged from 35- 65 years with histologically proven CRC and Histologically proven CRC with stage I, II, III 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: Active infection treated by antibiotic therapy or recent infection or recent antibiotic use; Severe cardiovascular and cerebrovascular diseases that could not tolerate radical surgery; Recent use of probiotics, prebiotics, or synbiotic; Evidence of immunodeficiency; Cancer stage IV Pregnancy, Recent/concurrent admission to ER 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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic Formula Capsule<br>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<br>* 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.<br>* Other names: Treatment;|
| Other: Control<br>In this intervention arm, the control arm will receive normal treatment without any probiotic | Drug: Control<br>* The Placebos will be coded in a specific label by a researcher.<br>|

What is the study measuring?
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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 fromNot 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 fromNot 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, Radiotherapy, immune system, Inflammatory markers, Life quality