Cardiovascular Risk Factors in Coeliac Disease: a Series of Studies

Coeliac Disease Clinical Trial

— ARCTIC  

Official title:

Cardiovascular Risk Factors in Coeliac Disease: a Series of Studies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05530070
• Other study ID #: 27521-5/2022/EÜIG
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: December 2026

Study information

• Verified date: May 2024
• Source: University of Pecs
• Contact: Judit Bajor, MD, PhD
• Phone: +36 72 536 000
• Email: bajor.judit[@]pte.hu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This investigation examines the most important cardiovascular risk factors (e.g., metabolic parameters, body composition) and their changes in coeliac disease. The series of studies allow to assess body composition and cardiovascular risk-related metabolic parameters of newly diagnosed and treated coeliac patients in their complexity and to test if they change during therapy. The interventional part of the investigation aims to answer the question if a dietary intervention mitigates the unfavorable effects of unbalanced diet.

Description:

The global prevalence of coeliac disease (CD) is increasing, which contributes to the disease's significant public health care burden. Body composition and metabolic parameters of coeliac patients differ from the healthy population. Patients with non-classical CD are not necessarily lean; they usually have normal body weight but can be even overweight or obese. In coeliac patients, bodyweight tends to elevate, whereas the body composition changes unfavourably during a gluten-free diet (GFD). A reason for gaining weight is the improvement of malabsorption but an important contributor is the nutrient composition of the GFD, which generally has a high calorie density with high carbohydrate and fat content while being low in fibre. While terminating or mitigating the inflammatory process - if done without adequate dietary control - a GFD can readily lead to weight gain and unfavourably metabolic consequences (e.g., dyslipidemia, fatty liver disease, insulin resistance). The result can be an increase in cardiovascular risk in CD patients with a normal or high body weight at diagnosis. However, limited information is available on the cardiovascular (CV) risk in coeliac disease, and the data are controversial. This study examines the body composition and cardiovascular risk-related metabolic parameters at the diagnosis and on a gluten-free diet in a Hungarian cohort of CD patients. The randomised controlled trial (RCT) investigates the effect of structured, repeated, group-based dietary education on the examined metabolic parameters and body composition.

This study aims to draw attention to a new aspect of the management of CD patients: from a metabolic and cardiovascular point of view. Findings will help to identify which parameters are beneficial to optimize and re-assess during follow-up in CD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: December 2026
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (applies to all subjects):

• Age should be over 18 years.

• Blood collection must be indicated with medical conditions.

• Signed informed consent.

Inclusion Criteria (applies to specific cohorts of patients):

• The diagnosis of CD should be set up according to the current guidelines (based on serology and histology in adults or as per the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guideline in children).

• The newly diagnosed CD patients should be on a gluten-containing diet.

• Patients following a GFD for at least 1 year should exhibit good dietary adherence.

• In the randomized controlled trial (RCT), strict dietary adherence will be established based on CD-specific serology (normal level of antibodies), urine gluten immunogenic peptides (negative urine test), and dietary interview (convincing knowledge on the GFD and positive attitude towards strict adherence). Adherence to the Mediterranean diet should be suboptimal (= 8 Medietrranean Diet Score). RCT-patients must have internet access and must be capable to attend the online sessions for 1 year.

• Control subjects should be free from CD according to the recent guidelines and should be on a gluten-containing diet.

Exclusion Criteria:

• Chronic conditions:

• Estimated glomerular filtration rate calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula is <60mL/min/1.73m2 (CKD3 or more severe kidney failure).

• Liver cirrhosis in Child-Pugh class B-C.

• Heart failure (New York Heart Association (NYHA) III-IV).

• Active malignant diseases.

• Any acute diseases or acute deterioration of underlying chronic conditions.

• Diseases that may be associated with clinically relevant malabsorption.

• Refractory CD.

• Pregnancy, lactation.

• Patients unable to understand the essentials of the informed consent.

• Lack of consent or withdrawal of consent.

Related Conditions & MeSH terms

• Celiac Disease
• Coeliac Disease

Intervention

Other:
• Dietary intervention
Patients will participate in a structured, group-based dietary counseling. Consultations will be organized online (Zoom meeting) lasting approximately 60 min/occasion. The intervention will include 6 sessions for 1 year (monthly for 5 months and finally at month 9). The aim of the counseling is to maintain a GFD and to develop a healthy lifestyle, in line with the Mediterranean diet.
• Standard of care
Patients will receive standard of care and baseline dietary education.

Diagnostic Test:
• Cardiovascular risk-related parameters
Anthropometric measurements (body height, body composition assessment-InBody 770), questionnaires (symptoms, quality of life, dietary adherence, diet quality, cardiovascular risk), assessment of sarcopenia (handgrip dynamometer), urine collection (dietary adherence - urine gluten immunogenic peptide detection), blood collection (immunological tests, hormone levels complemented with routine laboratory panel), transabdominal US examination to assess the extent of fatty liver disease.

Locations

Country	Name	City	State
Hungary	First Department of Medicine, Medical School, University of Pécs	Pécs	Baranya

Sponsors (1)

Lead Sponsor	Collaborator
University of Pecs

Country where clinical trial is conducted

Hungary, 

References & Publications (9)

Capristo E, Addolorato G, Mingrone G, De Gaetano A, Greco AV, Tataranni PA, Gasbarrini G. Changes in body composition, substrate oxidation, and resting metabolic rate in adult celiac disease patients after a 1-y gluten-free diet treatment. Am J Clin Nutr. 2000 Jul;72(1):76-81. doi: 10.1093/ajcn/72.1.76. — View Citation

Costa A, Brito GAP. Anthropometric Parameters in Celiac Disease: A Review on the Different Evaluation Methods and Disease Effects. J Nutr Metab. 2019 Sep 9;2019:4586963. doi: 10.1155/2019/4586963. eCollection 2019. — View Citation

Marciniak M, Szymczak-Tomczak A, Mahadea D, Eder P, Dobrowolska A, Krela-Kazmierczak I. Multidimensional Disadvantages of a Gluten-Free Diet in Celiac Disease: A Narrative Review. Nutrients. 2021 Feb 16;13(2):643. doi: 10.3390/nu13020643. — View Citation

Melini V, Melini F. Gluten-Free Diet: Gaps and Needs for a Healthier Diet. Nutrients. 2019 Jan 15;11(1):170. doi: 10.3390/nu11010170. — View Citation

Newnham ED, Shepherd SJ, Strauss BJ, Hosking P, Gibson PR. Adherence to the gluten-free diet can achieve the therapeutic goals in almost all patients with coeliac disease: A 5-year longitudinal study from diagnosis. J Gastroenterol Hepatol. 2016 Feb;31(2):342-9. doi: 10.1111/jgh.13060. — View Citation

Nunes-Silva JG, Nunes VS, Schwartz RP, Mlss Trecco S, Evazian D, Correa-Giannella ML, Nery M, Queiroz MS. Impact of type 1 diabetes mellitus and celiac disease on nutrition and quality of life. Nutr Diabetes. 2017 Jan 9;7(1):e239. doi: 10.1038/nutd.2016.43. — View Citation

Suarez-Gonzalez M, Bousono Garcia C, Jimenez Trevino S, Iglesias Cabo T, Diaz Martin JJ. Influence of nutrition education in paediatric coeliac disease: impact of the role of the registered dietitian: a prospective, single-arm intervention study. J Hum Nutr Diet. 2020 Dec;33(6):775-785. doi: 10.1111/jhn.12800. Epub 2020 Aug 12. — View Citation

Tucker E, Rostami K, Prabhakaran S, Al Dulaimi D. Patients with coeliac disease are increasingly overweight or obese on presentation. J Gastrointestin Liver Dis. 2012 Mar;21(1):11-5. — View Citation

Villanueva M, Oyarzun A, Leyton B, Gonzalez M, Navarro E, Canales P, Ossa C, Munoz MP, Bascunan KA, Araya M. Changes in Age at Diagnosis and Nutritional Course of Celiac Disease in the Last Two Decades. Nutrients. 2020 Jan 6;12(1):156. doi: 10.3390/nu12010156. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body height	Height in centimeters measured by a stadiometer.	4 years
Primary	Body weight	Weight in kilograms measured by an InBody 770 body composition analyzer.	4 years
Primary	Body mass index (BMI)	BMI in kg/m2 calculated by an InBody 770 body composition analyzer.	4 years
Primary	Body fat mass	Body fat mass in kilograms measured by an InBody 770 body composition analyzer.	4 years
Primary	Percent body fat	Percent body fat in percentage measured by an InBody 770 body composition analyzer.	4 years
Primary	Skeletal muscle mass	Skeletal muscle mass in kilograms measured by an InBody 770 body composition analyzer.	4 years
Primary	Visceral fat area	Visceral fat area in cm2 measured by an InBody 770 body composition analyzer.	4 years
Primary	Total body water	Total body water in liters measured by an InBody 770 body composition analyzer.	4 years
Secondary	Waist circumference	CV risk assessment will be performed by measuring waist circumference in centimeters.	4 years
Secondary	Blood pressure	CV risk assessment will be performed by measuring blood pressure in Hgmm.	4 years
Secondary	Fatty liver disease	Transabdominal ultrasonography will be used to assess the extent of fatty liver disease (based on non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS), with a score range of 0-3).	4 years
Secondary	Cardiovascular risk assessment	CV risk assessment will be performed by the Systematic Coronary Risk Evaluation (SCORE) chart.	4 years
Secondary	Coeliac disease-related symptoms	CD-related symptoms will be assessed by the Celiac Symptom Index (CSI).	4 years
Secondary	Coeliac disease-specific quality of life	CD-specific quality of life questionnaire will be also used (Celiac Disease Quality of Life (CD-QoL).	4 years
Secondary	Disease activity	Disease activity will be estimated by tissue transglutaminase (tTG) levels.	4 years
Secondary	Sarcopenia	Sarcopenia will be assessed based on body composition and handgrip strength via handgrip dynamometer.	4 years
Secondary	Triglyceride level	Triglyceride level in mmol/L.	4 years
Secondary	Cholesterol level	Cholesterol (total, HDL and LDL lipoproteins) level in mmol/L.	4 years
Secondary	Fasting glucose level	Fasting glucose level in mmol/L.	4 years
Secondary	Fasting insulin level	Fasting insulin level in mmol/L.	4 years
Secondary	Haemoglobin (Hb) A1c level	HbA1c level in percentage.	4 years
Secondary	Homeostasis Model Assessment (HOMA) index	HOMA index	4 years
Secondary	Bilirubin level	Bilirubin level in µmol/L.	4 years
Secondary	Uric acid level	Uric acid µmol/L.	4 years
Secondary	Urea level	Urea level in mmol/L.	4 years
Secondary	Creatinine level	Creatinine level in µmol/L.	4 years
Secondary	Sodium level	Sodium level in mmol/L.	4 years
Secondary	Potassium level	Potassium level in mmol/L.	4 years
Secondary	Calcium level	Calcium level in mmol/L.	4 years
Secondary	Vitamin D	Vitamin D level in ng/mL.	4 years
Secondary	Vitamin B12	Vitamin B12 level in pg/mL.	4 years
Secondary	Folic acid level	Folic acid level in µg/L.	4 years
Secondary	Iron level	Iron level in µmol/L.	4 years
Secondary	Ferritin level	Ferritin level in µg/L.	4 years
Secondary	Transferrin level	Transferrin level in g/L.	4 years
Secondary	Transferrin saturation	Transferrin saturation in percentage.	4 years
Secondary	International Normalized Ratio (INR)	INR	4 years
Secondary	Aspartate aminotransferase level	Aspartate aminotransferase level in U/L.	4 years
Secondary	Alanine aminotransferase level	Alanine aminotransferase in U/L.	4 years
Secondary	Fibrosis-4 (FIB-4) Index	FIB-4 Index for liver fibrosis.	4 years
Secondary	Total protein level	Total protein level in g/L.	4 years
Secondary	Albumin level	Albumin level in g/L.	4 years
Secondary	Immunoglobulins	Immunoglobulins in U/mL.	4 years
Secondary	High-sensitivity C-reactive protein (hs-CRP) level	hs-CRP level in mg/L.	4 years
Secondary	Fibrinogen level	Fibrinogen level in g/L.	4 years
Secondary	Blood counts	Blood counts in Giga/L.	4 years
Secondary	Homocysteine levels	Homocysteine levels in µmol/L.	4 years
Secondary	Interleukin-6 levels	Interleukin-6 levels in ng/L.	4 years
Secondary	Leptin levels	Leptin levels in ng/mL.	4 years
Secondary	Ghrelin levels	Ghrelin levels in pg/mL.	4 years
Secondary	Adiponectin levels	Adiponectin levels in µg/mL.	4 years
Secondary	Galectin-3 levels	Galectin-3 levels in ng/mL.	4 years
Secondary	Dietary interview	Dietary adherence will be determined by dietary interview provided by an expertise dietitian.	4 years
Secondary	Celiac Disease Adherence Test	Dietary adherence will be determined by the Celiac Disease Adherence Test (CDAT).	4 years
Secondary	Coeliac-specific antibodies	Dietary adherence will be determined by coeliac-specific antibodies (tissue transglutaminase (tTG) immunoglobulin (Ig) A/IgG and endomysium antibody levels (EMA) IgA) in U/mL.	4 years
Secondary	Urine gluten immunogenic peptide	Dietary adherence will be determined by urine gluten immunogenic peptide (GIP) measurement.	4 years
Secondary	Diet composition	The composition of a GFD will be evaluated with the indicator of adherence to the Mediterranean diet, the Mediterranean Diet Score (MDS).	4 years