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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Probiotic Formula Capsule; Drug: Placebos

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Jordan
  • Amman, Jordan
    • Jordan University Hospital

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: 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	Drug: Probiotic Formula Capsule; 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.; Other Names: Probiotics capsule; Probiotics supplement
Placebo Comparator: Placebos; 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; 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.; Other Names: Placebo oral capsule

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 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The level of White blood cell count (WBC)	The level of WBC as cells*10^9/l at both baseline and end line of follow up	Through study completion, an average of 1 year
The level of red blood cell count (RBC)	The level of RBC as cells*10^12/l at both baseline and end line of follow up	Through study completion, an average of 1 year
The mean corpuscular volume (MCV)	The MCV in fl at both baseline and end line of follow up	Through study completion, an average of 1 year
The mean corpuscular hemoglobin (MCH)	The MCH in pg at both baseline and end line of follow up	Through study completion, an average of 1 year
The mean corpuscular hemoglobin concentration (MCHC)	The MCH in g/dl at both baseline and end line of follow up	Through study completion, an average of 1 year
The Platelet count	The Platelet count as cells 10^9/ll at both baseline and end line of follow up	Through study completion, an average of 1 year
The of Hemoglobin	The Hemoglobin in g/dl at both baseline and end line of follow up	Through study completion, an average of 1 year
The mean platelet volume (MPV)	The MPV in fl at both baseline and end line of follow up	Through study completion, an average of 1 year
The level of lymphocytes	The number of lymphocytes cells as cells*10^9/L at both baseline and end line of follow up	Through study completion, an average of 1 year
The level of Monocytes	The number of Monocytes cells at both baseline and end line of follow up	Through study completion, an average of 1 year
The level of eosinophils	The number of eosinophils cells at both baseline and end line of follow up	Through study completion, an average of 1 year
The level of basophils	The number of basophils cells at both baseline and end line of follow up	Through study completion, an average of 1 year
The level of neutrophils	The number of neutrophils cells at both baseline and end line of follow up	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: University of Jordan
• Investigators: Study Chair: Mohammed Isam Yamani, Pro.Dr, University of Jordan; Study Chair: Reema F Tayyem, Pro.Dr, University of Jordan

Publications and helpful links

General Publications

• Abraham BP, Quigley EMM. Probiotics in Inflammatory Bowel Disease. Gastroenterol Clin North Am. 2017 Dec;46(4):769-782. doi: 10.1016/j.gtc.2017.08.003. Epub 2017 Oct 3.
• Araya M, Morelli L, Reid G, et al. (2002), Guidelines for the evaluation of probiotics in food. Joint FAO/WHO Working Group report on drafting guidelines for the evaluation of probiotics in food, London; (ON, Canada). ftp://ftp.fao.org/es/esn/food/wgreport2.pdf (Accessed 19March, 2018).
• Bamias G, Corridoni D, Pizarro TT, Cominelli F. New insights into the dichotomous role of innate cytokines in gut homeostasis and inflammation. Cytokine. 2012 Sep;59(3):451-9. doi: 10.1016/j.cyto.2012.06.014. Epub 2012 Jul 12.
• Bengtsson J, Adlerberth I, Ostblom A, Saksena P, Oresland T, Borjesson L. Effect of probiotics (Lactobacillus plantarum 299 plus Bifidobacterium Cure21) in patients with poor ileal pouch function: a randomised controlled trial. Scand J Gastroenterol. 2016 Sep;51(9):1087-92. doi: 10.3109/00365521.2016.1161067. Epub 2016 May 6.
• Cai S, Kandasamy M, Rahmat JN, Tham SM, Bay BH, Lee YK, Mahendran R. Lactobacillus rhamnosus GG Activation of Dendritic Cells and Neutrophils Depends on the Dose and Time of Exposure. J Immunol Res. 2016;2016:7402760. doi: 10.1155/2016/7402760. Epub 2016 Jul 20.
• Dargahi N, Johnson J, Donkor O, Vasiljevic T, Apostolopoulos V. Immunomodulatory effects of probiotics: Can they be used to treat allergies and autoimmune diseases? Maturitas. 2019 Jan;119:25-38. doi: 10.1016/j.maturitas.2018.11.002. Epub 2018 Nov 12.
• de Moreno de Leblanc A, Del Carmen S, Zurita-Turk M, Santos Rocha C, van de Guchte M, Azevedo V, Miyoshi A, Leblanc JG. Importance of IL-10 modulation by probiotic microorganisms in gastrointestinal inflammatory diseases. ISRN Gastroenterol. 2011;2011:892971. doi: 10.5402/2011/892971. Epub 2011 Feb 8.
• Feuerstein JD, Moss AC, Farraye FA. Ulcerative Colitis. Mayo Clin Proc. 2019 Jul;94(7):1357-1373. doi: 10.1016/j.mayocp.2019.01.018. Erratum In: Mayo Clin Proc. 2019 Oct;94(10):2149.
• Gajendran M, Loganathan P, Jimenez G, Catinella AP, Ng N, Umapathy C, Ziade N, Hashash JG. A comprehensive review and update on ulcerative colitis. Dis Mon. 2019 Dec;65(12):100851. doi: 10.1016/j.disamonth.2019.02.004. Epub 2019 Mar 2.
• Guandalini S, Sansotta N. Probiotics in the Treatment of Inflammatory Bowel Disease. Adv Exp Med Biol. 2019;1125:101-107. doi: 10.1007/5584_2018_319.
• Kabeerdoss J, Devi RS, Mary RR, Prabhavathi D, Vidya R, Mechenro J, Mahendri NV, Pugazhendhi S, Ramakrishna BS. Effect of yoghurt containing Bifidobacterium lactis Bb12(R) on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers. Nutr J. 2011 Dec 23;10:138. doi: 10.1186/1475-2891-10-138.
• Kaplan GG, Ng SC. Globalisation of inflammatory bowel disease: perspectives from the evolution of inflammatory bowel disease in the UK and China. Lancet Gastroenterol Hepatol. 2016 Dec;1(4):307-316. doi: 10.1016/S2468-1253(16)30077-2. Epub 2016 Nov 10.
• Konishi H, Fujiya M, Tanaka H, Ueno N, Moriichi K, Sasajima J, Ikuta K, Akutsu H, Tanabe H, Kohgo Y. Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis. Nat Commun. 2016 Aug 10;7:12365. doi: 10.1038/ncomms12365.
• Agraib LM, Yamani MI, Tayyem R, Abu-Sneineh AT, Rayyan YM. Probiotic supplementation induces remission and changes in the immunoglobulins and inflammatory response in active ulcerative colitis patients: A pilot, randomized, double-blind, placebo-controlled study. Clin Nutr ESPEN. 2022 Oct;51:83-91. doi: 10.1016/j.clnesp.2022.08.020. Epub 2022 Aug 20.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Actual): March 1, 2022
• Study Completion (Actual): March 10, 2022

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 20, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Probiotics; Ulcerative Colitis; Inflammatory markers; immune system
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 2019/385

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The center (Jordan University hospital) 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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No