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

NCT ID: NCT04223479

Last Updated: 2024-09-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-15

Study Completion Date

2022-03-10

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).

Conditions

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Ulcerative Colitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type EXPERIMENTAL

Probiotic Formula Capsule

Intervention Type 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.

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.

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Probiotics capsule Probiotics supplement Placebo oral capsule

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
Minimum Eligible Age

35 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Jordan

OTHER

Sponsor Role lead

Responsible Party

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Lana M. Agraib

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mohammed Isam Yamani, Pro.Dr

Role: STUDY_CHAIR

University of Jordan

Reema F Tayyem, Pro.Dr

Role: STUDY_CHAIR

University of Jordan

Locations

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Jordan University Hospital

Amman, , Jordan

Site Status

Countries

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Jordan

References

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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.

Reference Type BACKGROUND
PMID: 29173520 (View on PubMed)

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).

Reference Type 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.

Reference Type BACKGROUND
PMID: 22795953 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27150635 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27525288 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30502748 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21991534 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31272578 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30837080 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30632114 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22196482 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28404201 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27507542 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37498369 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36184252 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2019/385

Identifier Type: -

Identifier Source: org_study_id

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