Intestinal Permeability, Nutritional Status and Quality of Life in Celiac Disease

NCT ID: NCT04351828

Last Updated: 2020-04-21

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 44 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-11-05
• Study Completion Date: 2019-04-19

Brief Summary

Celiac disease is defined as an autoimmune enteropathy with malabsorption of gluten protein. In recent studies, it has been stated that in individuals diagnosed with celiac disease, intestinal epithelial barrier integrity is impaired. Increased zonulin concentration in blood is considered as an indicator of increased intestinal permeability.

Gluten-free diet is the only treatment of celiac disease. Adherence to gluten free diet provides decreasing of intestinal permeability however gluten free diet has different aspects on nutritional status and health related quality of life in people with celiac disease.

The aim of this study is to determine nutritional status, intestinal permeability and quality of life in people with celiac disease. In the study,it primarily hypothesized that celiac patients noncompliant to gluten-free diet may have increased circulating levels of zonulin and increased intestinal permeability compared to celiac patients compliant to gluten-free diet.

Detailed Description

Celiac disease is defined as an autoimmune enteropathy that progresses with malabsorption of gluten protein found in wheat, barley, rye and small intestinal mucosal inflammation in individuals with genetic predisposition. Disruption of intestinal barrier integrity play role in the pathogenesis of celiac disease. Zonulin levels increase in the disruption of intestinal permeability in celiac patients.

At the present, the only treatment of celiac disease is life-long gluten-free diet and it requires strict gluten elimination . With compliance to gluten-free diet, thickening of intestinal mucosal layer, decreasing of villi atrophy and decreasing of transcellular infiltration are observed. In other studies, it was stated that adherence to gluten-free diet can repair intestinal permeability and decrease zonulin levels.

While compliance to gluten-free diet is a key point to prevent progression of the disease, nutritional quality of the gluten-free diet affects nutritional status of patients. Moreover,restricted diets in terms of energy or various nutrients affect health-related quality of life. In studies examining all aspects of celiac disease, it has been stated that health-related factors reduce the quality of life in celiac patients.

In conclusion, this study aims to investigate the presence of intestinal permeability with serum zonulin levels in celiac patients, to evaluate nutritional status of patients with anthropometric measurements and food consumption records, and to determine quality of life of patients with validated celiac disease questionnaire. This study in Turkey, is also first study that investigate all these three factors.

Conditions

Celiac Disease; Nutritional Deficiency; Quality of Life

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Celiac patients compliant to gluten-free diet (GFD)

People with celiac disease who compliant to gluten-free diet (GFD) when they accepted in the study

Blood draw once a time

Intervention Type: PROCEDURE

Investigation of intestinal permeability by measuring serum zonulin levels in blood sample

Celiac patients non-compliant to gluten-free diet(NGFD)

People with celiac disease who noncompliant to the gluten-free diet (NGFD) group when they accepted in the study

Blood draw once a time

Intervention Type: PROCEDURE

Investigation of intestinal permeability by measuring serum zonulin levels in blood sample

Interventions

Blood draw once a time

Investigation of intestinal permeability by measuring serum zonulin levels in blood sample

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• To be between the ages of 18-64,
• To be literate,
• To have positive serological anti tissue transglutaminase immunoglobulin A antibodies value,
• To have a small intestinal biopsy proven celiac disease diagnosis at the time of gastrointestinal endoscopy
• To be volunteer by signing the informed consent form.

Exclusion Criteria

• To have another autoimmune disease such as type 1 diabetes, psoriasis, hashimoto's thyroiditis, rheumatoid arthritis, systemic lupus erythematosus,
• To be in pregnancy or lactation period,
• Taking probiotic/ prebiotics supplements in the last 2 months,
• Taking antibiotics or non-steroidal antiinflammatory drugs in the last 1 week.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Marmara University

OTHER

Sponsor Role: lead

Responsible Party

Yeşim Öztekin

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yeşim Öztekin

Role: PRINCIPAL_INVESTIGATOR

Marmara University

Locations

Marmara University Institute of Health Sciences

Istanbul, Maltepe, Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

Ajamian M, Steer D, Rosella G, Gibson PR. Serum zonulin as a marker of intestinal mucosal barrier function: May not be what it seems. PLoS One. 2019 Jan 14;14(1):e0210728. doi: 10.1371/journal.pone.0210728. eCollection 2019.

Reference Type: BACKGROUND

PMID: 30640940 (View on PubMed)

Bai JC, Ciacci C. World Gastroenterology Organisation Global Guidelines: Celiac Disease February 2017. J Clin Gastroenterol. 2017 Oct;51(9):755-768. doi: 10.1097/MCG.0000000000000919. No abstract available.

Reference Type: BACKGROUND

PMID: 28877080 (View on PubMed)

Burger JPW, de Brouwer B, IntHout J, Wahab PJ, Tummers M, Drenth JPH. Systematic review with meta-analysis: Dietary adherence influences normalization of health-related quality of life in coeliac disease. Clin Nutr. 2017 Apr;36(2):399-406. doi: 10.1016/j.clnu.2016.04.021. Epub 2016 Apr 30.

Reference Type: BACKGROUND

PMID: 27179800 (View on PubMed)

C D, Berry N, Vaiphei K, Dhaka N, Sinha SK, Kochhar R. Quality of life in celiac disease and the effect of gluten-free diet. JGH Open. 2018 Jun 6;2(4):124-128. doi: 10.1002/jgh3.12056. eCollection 2018 Aug.

Reference Type: BACKGROUND

PMID: 30483576 (View on PubMed)

Fasano A. Intestinal zonulin: open sesame! Gut. 2001 Aug;49(2):159-62. doi: 10.1136/gut.49.2.159. No abstract available.

Reference Type: BACKGROUND

PMID: 11454785 (View on PubMed)

Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1096-100. doi: 10.1016/j.cgh.2012.08.012. Epub 2012 Aug 16.

Reference Type: BACKGROUND

PMID: 22902773 (View on PubMed)

Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C. The Oslo definitions for coeliac disease and related terms. Gut. 2013 Jan;62(1):43-52. doi: 10.1136/gutjnl-2011-301346. Epub 2012 Feb 16.

Reference Type: BACKGROUND

PMID: 22345659 (View on PubMed)

Schumann M, Siegmund B, Schulzke JD, Fromm M. Celiac Disease: Role of the Epithelial Barrier. Cell Mol Gastroenterol Hepatol. 2017 Jan 14;3(2):150-162. doi: 10.1016/j.jcmgh.2016.12.006. eCollection 2017 Mar.

Reference Type: BACKGROUND

PMID: 28275682 (View on PubMed)

Theethira TG, Dennis M, Leffler DA. Nutritional consequences of celiac disease and the gluten-free diet. Expert Rev Gastroenterol Hepatol. 2014 Feb;8(2):123-9. doi: 10.1586/17474124.2014.876360.

Reference Type: BACKGROUND

PMID: 24417260 (View on PubMed)

Vici G, Belli L, Biondi M, Polzonetti V. Gluten free diet and nutrient deficiencies: A review. Clin Nutr. 2016 Dec;35(6):1236-1241. doi: 10.1016/j.clnu.2016.05.002. Epub 2016 May 7.

Reference Type: BACKGROUND

PMID: 27211234 (View on PubMed)

Duerksen DR, Wilhelm-Boyles C, Veitch R, Kryszak D, Parry DM. A comparison of antibody testing, permeability testing, and zonulin levels with small-bowel biopsy in celiac disease patients on a gluten-free diet. Dig Dis Sci. 2010 Apr;55(4):1026-31. doi: 10.1007/s10620-009-0813-5. Epub 2009 Apr 28.

Reference Type: RESULT

PMID: 19399613 (View on PubMed)

Aksan A, Mercanligil SM, Hauser W, Karaismailoglu E. Validation of the Turkish version of the Celiac Disease Questionnaire (CDQ). Health Qual Life Outcomes. 2015 Jun 19;13:82. doi: 10.1186/s12955-015-0272-y.

Reference Type: RESULT

PMID: 26088079 (View on PubMed)

Barone M, Della Valle N, Rosania R, Facciorusso A, Trotta A, Cantatore FP, Falco S, Pignatiello S, Viggiani MT, Amoruso A, De Filippis R, Di Leo A, Francavilla R. A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects. Eur J Clin Nutr. 2016 Jan;70(1):23-7. doi: 10.1038/ejcn.2015.114. Epub 2015 Jul 15.

Reference Type: RESULT

PMID: 26173865 (View on PubMed)

Duerksen DR, Wilhelm-Boyles C, Parry DM. Intestinal permeability in long-term follow-up of patients with celiac disease on a gluten-free diet. Dig Dis Sci. 2005 Apr;50(4):785-90. doi: 10.1007/s10620-005-2574-0.

Reference Type: RESULT

PMID: 15844719 (View on PubMed)

Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, Goldblum SE. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000 Apr 29;355(9214):1518-9. doi: 10.1016/S0140-6736(00)02169-3.

Reference Type: RESULT

PMID: 10801176 (View on PubMed)

Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008 Nov;173(5):1243-52. doi: 10.2353/ajpath.2008.080192. Epub 2008 Oct 2.

Reference Type: RESULT

PMID: 18832585 (View on PubMed)

Hauser W, Gold J, Stallmach A, Caspary WF, Stein J. Development and validation of the Celiac Disease Questionnaire (CDQ), a disease-specific health-related quality of life measure for adult patients with celiac disease. J Clin Gastroenterol. 2007 Feb;41(2):157-66. doi: 10.1097/01.mcg.0000225516.05666.4e.

Reference Type: RESULT

PMID: 17245214 (View on PubMed)

Hall NJ, Rubin G, Charnock A. Systematic review: adherence to a gluten-free diet in adult patients with coeliac disease. Aliment Pharmacol Ther. 2009 Aug 15;30(4):315-30. doi: 10.1111/j.1365-2036.2009.04053.x. Epub 2009 May 26.

Reference Type: RESULT

PMID: 19485977 (View on PubMed)

Kabbani TA, Goldberg A, Kelly CP, Pallav K, Tariq S, Peer A, Hansen J, Dennis M, Leffler DA. Body mass index and the risk of obesity in coeliac disease treated with the gluten-free diet. Aliment Pharmacol Ther. 2012 Mar;35(6):723-9. doi: 10.1111/j.1365-2036.2012.05001.x. Epub 2012 Feb 8.

Reference Type: RESULT

PMID: 22316503 (View on PubMed)

Lammers KM, Lu R, Brownley J, Lu B, Gerard C, Thomas K, Rallabhandi P, Shea-Donohue T, Tamiz A, Alkan S, Netzel-Arnett S, Antalis T, Vogel SN, Fasano A. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology. 2008 Jul;135(1):194-204.e3. doi: 10.1053/j.gastro.2008.03.023. Epub 2008 Mar 21.

Reference Type: RESULT

PMID: 18485912 (View on PubMed)

Leffler DA, Edwards George JB, Dennis M, Cook EF, Schuppan D, Kelly CP. A prospective comparative study of five measures of gluten-free diet adherence in adults with coeliac disease. Aliment Pharmacol Ther. 2007 Nov 1;26(9):1227-35. doi: 10.1111/j.1365-2036.2007.03501.x.

Reference Type: RESULT

PMID: 17944737 (View on PubMed)

Mishra A, Prakash S, Sreenivas V, Das TK, Ahuja V, Gupta SD, Makharia GK. Structural and Functional Changes in the Tight Junctions of Asymptomatic and Serology-negative First-degree Relatives of Patients With Celiac Disease. J Clin Gastroenterol. 2016 Aug;50(7):551-60. doi: 10.1097/MCG.0000000000000436.

Reference Type: RESULT

PMID: 26535478 (View on PubMed)

Miranda J, Lasa A, Bustamante MA, Churruca I, Simon E. Nutritional differences between a gluten-free diet and a diet containing equivalent products with gluten. Plant Foods Hum Nutr. 2014 Jun;69(2):182-7. doi: 10.1007/s11130-014-0410-4.

Reference Type: RESULT

PMID: 24578088 (View on PubMed)

Paganizza S, Zanotti R, D'Odorico A, Scapolo P, Canova C. Is Adherence to a Gluten-Free Diet by Adult Patients With Celiac Disease Influenced by Their Knowledge of the Gluten Content of Foods? Gastroenterol Nurs. 2019 Jan/Feb;42(1):55-64. doi: 10.1097/SGA.0000000000000368.

Reference Type: RESULT

PMID: 30688709 (View on PubMed)

Rondanelli M, Faliva MA, Gasparri C, Peroni G, Naso M, Picciotto G, Riva A, Nichetti M, Infantino V, Alalwan TA, Perna S. Micronutrients Dietary Supplementation Advices for Celiac Patients on Long-Term Gluten-Free Diet with Good Compliance: A Review. Medicina (Kaunas). 2019 Jul 3;55(7):337. doi: 10.3390/medicina55070337.

Reference Type: RESULT

PMID: 31277328 (View on PubMed)

Serin, Y., & Akbulut, G. Nutritional Status and Health-Related Quality of Life in Adlt Patients With Celiac Disease. CBU International Conference Proceedings 2018; 6: 952-959. https://doi.org/10.12955/cbup.v6.1277

Reference Type: RESULT

Taetzsch A, Das SK, Brown C, Krauss A, Silver RE, Roberts SB. Are Gluten-Free Diets More Nutritious? An Evaluation of Self-Selected and Recommended Gluten-Free and Gluten-Containing Dietary Patterns. Nutrients. 2018 Dec 3;10(12):1881. doi: 10.3390/nu10121881.

Reference Type: RESULT

PMID: 30513876 (View on PubMed)

Ukkola A, Maki M, Kurppa K, Collin P, Huhtala H, Kekkonen L, Kaukinen K. Changes in body mass index on a gluten-free diet in coeliac disease: a nationwide study. Eur J Intern Med. 2012 Jun;23(4):384-8. doi: 10.1016/j.ejim.2011.12.012. Epub 2012 Jan 28.

Reference Type: RESULT

PMID: 22560391 (View on PubMed)

Vojdani A, Vojdani E, Kharrazian D. Fluctuation of zonulin levels in blood vs stability of antibodies. World J Gastroenterol. 2017 Aug 21;23(31):5669-5679. doi: 10.3748/wjg.v23.i31.5669.

Reference Type: RESULT

PMID: 28883692 (View on PubMed)

Related Links

http://www.euro.who.int/en/health-topics/disease-prevention/nutrition/a-healthy-lifestyle/body-mass-index-bmi

World Health Organization (WHO) classification of BMI

http://dosyasb.saglik.gov.tr/eklenti/10915,tuber-turkiye-beslenme-rehberipdf.pdf

Dietary Guidelines for Turkey (TUBER)

Other Identifiers

SAG-C-YLP-121218-0630

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

09.2018.359

Identifier Type: -

Identifier Source: org_study_id