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

NCT04223479 | Completed Phase 2 Results DMC

• 1 other identifier: 2019/385
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; immune system; Inflammatory markers; Probiotics

Outcome Measures

Primary Outcomes (8)

• The Level of Immunoglobulin (Ig) A

  The level of Immunoglobulin (Ig) A in mg/dL was tested at the end of follow-up (after 6 weeks of follow-up) based on an Immunoturbidimetric assay using Cobas-C501

  at the end of 6 weeks of follow-up

• The Level of Immunoglobulin (Ig) G

  The level of Immunoglobulin (Ig) G in mg/dL was tested at the end of follow-up (after 6 weeks of follow-up) based on an Immunoturbidimetric assay using Cobas-C501

  at the end of 6 weeks of follow up

• The Level of Immunoglobulin (Ig) M

  The level of Immunoglobulin (Ig) M in mg/dL was tested at the end of follow-up (after 6 weeks of follow-up) based on an Immunoturbidimetric assay using Cobas-C501

  at the end of 6 weeks of follow-up

• The Level of Interleukin (IL)-6

  The Level of Interleukin (IL)-6 in pg/ml measured aat the end of follow-up (after 6 weeks of follow-up) by a two-site sandwich Enzyme-Linked Immunosorbent Assay (ELISA)

  at the end of 6 weeks of follow-up

• The Level of Interleukin (IL)-1

  The Level of Interleukin (IL)-1 in pg/ml measured at the end of follow-up (after 6 weeks of follow-up) by a two-site sandwich Enzyme-Linked Immunosorbent Assay (ELISA)

  at the end of 6 weeks of follow-up

• The Level of Interleukin (IL)-10

  The Level of Interleukin (IL)-10 in pg/ml was measured at the end of follow-up (after 6 weeks of follow-up) by a two-site sandwich Enzyme-Linked Immunosorbent Assay (ELISA)

  at the endo f 6 weeks of follow-up

• The Level of Tumor Necrosis Factor (TNF)-α

  The Level of TNF-α in pg/ml measured at the end of follow-up (after 6 weeks of follow-up) by a two-site sandwich Enzyme-Linked Immunosorbent Assay (ELISA)

  at the endo of 6weeks of follow-up

• The Level of C-reactive Protein (CRP)

  The Level of CRP in mg/ml measured at the end of follow-up (after 6 weeks of follow-up) based on an Immunoturbidimetric assay using Cobas-C501

  at the end of 6 weeks of follow-up

Secondary Outcomes (1)

• Quality of Life of Patients

  at the end of 6 weeks of follow-up

Other Outcomes (13)

• The Level of White Blood Cell Count (WBC)

  at the end of 6 weeks of follow-up

• The Level of Red Blood Cell Count (RBC)

  at the end of 6 weeks of follow-up

• The Mean Corpuscular Volume (MCV)

  at the end of 6 weeks of follow-up

Study Arms (2)

Probiotic Formula Capsule

EXPERIMENTAL

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

Placebos

PLACEBO COMPARATOR

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

Interventions

Probiotic Formula Capsule DRUG

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.

Also known as: Probiotics capsule, Probiotics supplement

Probiotic Formula Capsule

Placebos DRUG

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.

Also known as: Placebo oral capsule

Placebos

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Jordan: lead

Study Sites (1)

Jordan University Hospital

Amman, Jordan

Location

Related Publications (15)

• 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.

  PMID: 29173520 BACKGROUND

• 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).

  BACKGROUND

• 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.

  PMID: 22795953 BACKGROUND

• 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.

  PMID: 27150635 BACKGROUND

• 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.

  PMID: 27525288 BACKGROUND

• 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.

  PMID: 30502748 BACKGROUND

• 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.

  PMID: 21991534 BACKGROUND

• 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.

  PMID: 31272578 BACKGROUND

• 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.

  PMID: 30837080 BACKGROUND

• 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.

  PMID: 30632114 BACKGROUND

• 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.

  PMID: 22196482 BACKGROUND

• 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.

  PMID: 28404201 BACKGROUND

• 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.

  PMID: 27507542 BACKGROUND

• Rayyan YM, Agraib LM, Alkhatib B, Yamani MI, Abu-Sneineh AT, Tayyem RF. Does probiotic supplementation improve quality of life in mild-to-moderately active ulcerative colitis patients in Jordan? A secondary outcome of the randomized, double-blind, placebo-controlled study. Eur J Nutr. 2023 Oct;62(7):3069-3077. doi: 10.1007/s00394-023-03207-8. Epub 2023 Jul 27.

  PMID: 37498369 DERIVED

• 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.

  PMID: 36184252 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Results Point of Contact

• Title: Lana M. Agraib
• Organization: The University of Jordan

lanamg2007@yahoo.com

+962

Study Officials

• Mohammed Isam Yamani, Pro.Dr

  University of Jordan

  STUDY CHAIR

• Reema F Tayyem, Pro.Dr

  University of Jordan

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: January 10, 2020
• Study Start: January 15, 2020
• Primary Completion: March 1, 2022
• Study Completion: March 10, 2022
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

JO (1)