Effect of Probiotic Supplementation on the Immune System in Patients With Ulcerative Colitis in Amman, Jordan

Study Overview
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Brief Summary
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Ulcerative colitis (UC) is a chronic Inflammatory bowel disease (IBD) that most likely results from the interaction between various environmental and genetic factors. Using probiotics as an adjunct to medical therapy might be useful in the treatment of UC and improving the symptoms of the disease. The result of studies that investigate the role of Probiotics supplementation in improving the inflammatory response, immune response and life quality of patients with the UC is not conclusive. So, this study aimed to study the effect of probiotics on the response of inflammatory markers, immune response, and quality of life in patients with UC. An interventional double-blind randomized clinical trial (RCT) design will be used in this study. Forty patients will be recruited and randomly assigned to the placebo group (n=20) to receive 3 times a day placebo capsules; and probiotics group (n=20), to receive 3 times a day probiotic supplement. The demographic data, anthropometric measurements, IBD Quality of Life Questionnaire and blood samples will be collected at baseline and after 6 weeks of follow up. 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 UC patients to raise the immune system as well as improving their quality of life.

Detailed Description
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To meet the objectives of the study, an interventional double-blind randomized clinical trial (RCT) design will be used in this study. A placebo group will be included in parallel with the treatment group in this trail. Forty patients (aged 35-65 years) who diagnosed with mild to moderately active UC will be recruited conveniently from the gastroenterology section, the IBD clinic at the Jordan University Hospital, Amman, Jordan. Patients who meet the inclusion criteria and agree to participate will be centrally randomized to probiotic supplementation group or placebo group using computer-generated random numbers, that balanced allocation to groups A and B: in successive blocks each containing 20 patients each stratified by gender. The duration of the intervention will be 6 weeks. For the participants, the Jordan University 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 will randomly be assigned to the placebo group (n=20), to receive 3 times a day placebo capsules contain polysaccharides, without any viable probiotics matching the probiotic capsules in appearance, smell, and taste; and probiotics group (n=20), to receive 3 times a day probiotic supplement. The administration of supplements will be under the supervision of the treating physician. The blood sample will be collected at baseline and at the end of 6 weeks of follow up. 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 of the follow-up, IBD Quality of Life Questionnaire 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 Probiotic Supplementation on the Immune System in Patients With Ulcerative Colitis in Amman, Jordan

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Probiotic Formula Capsule
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients, Age between 35 -65 years, Diagnosed with UC established by colonoscopy and histology, and suffering from mild to moderate UC as defined by Modified Mayo Disease Activity Index (MMDAI) (score 3-9). Exclusion Criteria: Patients with age <35 years, >65 years, Pregnancy, planned pregnancy, breastfeeding women, Evidence of severe disease (MMDAI >10), Concurrent enteric infection, Use of antibiotics, Change in the dose of oral 5-aminosalicylic acid (5-ASA) within the past 4weeks, and use of rectal 5-ASA or steroids within 7 days before entry into the study, Received any investigational medicines within 3months, If they have significant hepatic, renal, endocrine, respiratory, neurological, or cardiovascular diseases

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: 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 | Drug: Probiotic Formula Capsule<br>* The Probiotic will be coded in a specific label by a researcher who will not be in contact with the participants and administrated randomly based on gender in a double-blind manner. The patient will receive 2 bottles of the drug every 2 weeks and will be followed weekly for 6 weeks.<br>* Other names: Probiotics supplement;|
| Placebo Comparator: Placebos<br>In this intervention arm Placebo arm received three oral viable capsules daily, containing polysaccharides, without any viable probiotics matching the probiotic capsules in appearance, smell, and taste. | Drug: Placebos<br>* The Placebos will be coded in a specific label by a researcher who will not be in contact with the participants and administrated randomly based on gender in a double-blind manner. The patient will receive 2 bottles of the placebo every 2 weeks and will be followed weekly for 6 weeks.<br>* Other names: Placebo oral capsule;|

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 mg/dL at both baseline and end line of follow up | Through study completion, an average of 1 year | 
| The level of Immunoglobulin (Ig) G | The level of Immunoglobulin (Ig) G in mg/dL at both baseline and end line of follow up | Through study completion, an average of 1 year | 
| The level of Immunoglobulin (Ig) M | The level of Immunoglobulin (Ig) M in mg/dL at both baseline and end line of follow up | 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 follow up | 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 follow up | 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 follow up | 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 follow up | 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 follow up | Through study completion, an average of 1 year | 

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 Short Quality of Life in Inflammatory Bowel Disease Questionnaire (SIBDQ). The SIBDQ contains 10 questions for 4 functional scales (Bowel, Systemic, emotional, and social). For each question, there a regraded responses on a7-point Likert scale ranging from one (representing the ''worst'' aspect) to seven (representing the ''best'' aspect). Total SIBDQ scores range from 10 to 70, with higher scores reflecting better well-being. | 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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Ulcerative Colitis, immune system, Inflammatory markers, Probiotics