Cardiovascular Risk Factors in Coeliac Disease: a Series of Studies (ARCTIC)

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.

Study Overview

• Status: Recruiting
• Conditions: Coeliac Disease
• Intervention / Treatment: Diagnostic test: Cardiovascular risk-related parameters; Other: Standard of care; Other: Dietary intervention

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Judit Bajor, MD, PhD; Phone Number: +36 72 536 000; Email: bajor.judit@pte.hu

Study Locations

• Hungary
  • Baranya
    • Pécs, Baranya, Hungary, 7624
      • Recruiting
      • First Department of Medicine, Medical School, University of Pécs
      • Contact: Judit Bajor, MD, PhD; Phone Number: +36 72 536 000; Email: bajor.judit@pte.hu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dietary intervention; Patients randomized to the dietary intervention group.	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.; 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.
Active Comparator: Standard of care; Patients randomized to the standard of care group.	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.; Other: Standard of care; Patients will receive standard of care and baseline dietary education.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent body fat	Percent body fat in percentage measured by an InBody 770 body composition analyzer.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Waist circumference	CV risk assessment will be performed by measuring waist circumference in centimeters.	1 year
Blood pressure	CV risk assessment will be performed by measuring blood pressure in Hgmm.	1 year
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).	1 year
Cardiovascular risk assessment	CV risk assessment will be performed by the Systematic Coronary Risk Evaluation (SCORE) chart.	1 year
Coeliac disease-related symptoms	CD-related symptoms will be assessed by the Celiac Symptom Index (CSI).	1 year
Coeliac disease-specific quality of life	CD-specific quality of life questionnaire will be also used (Celiac Disease Quality of Life (CD-QoL).	1 year
Disease activity	Disease activity will be estimated by tissue transglutaminase (tTG) levels.	1 year
Sarcopenia	Sarcopenia will be assessed based on body composition and handgrip strength via handgrip dynamometer.	1 year
Triglyceride level	Triglyceride level in mmol/L.	1 year
Cholesterol level	Cholesterol (total, HDL and LDL lipoproteins) level in mmol/L.	1 year
Fasting glucose level	Fasting glucose level in mmol/L.	1 year
Fasting insulin level	Fasting insulin level in mmol/L.	1 year
Haemoglobin (Hb) A1c level	HbA1c level in percentage.	1 year
Homeostasis Model Assessment (HOMA) index	HOMA index	1 year
Bilirubin level	Bilirubin level in µmol/L.	1 year
Uric acid level	Uric acid µmol/L.	1 year
Urea level	Urea level in mmol/L.	1 year
Creatinine level	Creatinine level in µmol/L.	1 year
Sodium level	Sodium level in mmol/L.	1 year
Potassium level	Potassium level in mmol/L.	1 year
Calcium level	Calcium level in mmol/L.	1 year
Vitamin D	Vitamin D level in ng/mL.	1 year
Vitamin B12	Vitamin B12 level in pg/mL.	1 year
Folic acid level	Folic acid level in µg/L.	1 year
Iron level	Iron level in µmol/L.	1 year
Ferritin level	Ferritin level in µg/L.	1 year
Transferrin level	Transferrin level in g/L.	1 year
Transferrin saturation	Transferrin saturation in percentage.	1 year
International Normalized Ratio (INR)	INR	1 year
Aspartate aminotransferase level	Aspartate aminotransferase level in U/L.	1 year
Alanine aminotransferase level	Alanine aminotransferase in U/L.	1 year
Fibrosis-4 (FIB-4) Index	FIB-4 Index for liver fibrosis.	1 year
Total protein level	Total protein level in g/L.	1 year
Albumin level	Albumin level in g/L.	1 year
Immunoglobulins	Immunoglobulins in U/mL.	1 year
High-sensitivity C-reactive protein (hs-CRP) level	hs-CRP level in mg/L.	1 year
Fibrinogen level	Fibrinogen level in g/L.	1 year
Blood counts	Blood counts in Giga/L.	1 year
Homocysteine levels	Homocysteine levels in µmol/L.	1 year
Interleukin-6 levels	Interleukin-6 levels in ng/L.	1 year
Leptin levels	Leptin levels in ng/mL.	1 year
Ghrelin levels	Ghrelin levels in pg/mL.	1 year
Adiponectin levels	Adiponectin levels in µg/mL.	1 year
Galectin-3 levels	Galectin-3 levels in ng/mL.	1 year
Dietary interview	Dietary adherence will be determined by dietary interview provided by an expertise dietitian.	1 year
Celiac Disease Adherence Test	Dietary adherence will be determined by the Celiac Disease Adherence Test (CDAT).	1 year
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.	1 year
Urine gluten immunogenic peptide	Dietary adherence will be determined by urine gluten immunogenic peptide (GIP) measurement.	1 year
Diet composition	The composition of a GFD will be evaluated with the indicator of adherence to the Mediterranean diet, the Mediterranean Diet Score (MDS).	1 year
Body height	Height in centimeters measured by a stadiometer.	1 year
Body weight	Weight in kilograms measured by an InBody 770 body composition analyzer.	1 year
Body mass index	Body mass index in kg/m2 calculated by an InBody 770 body composition analyzer.	1 year
Body fat mass	Body fat mass in kilograms measured by an InBody 770 body composition analyzer.	1 year
Skeletal muscle mass	Skeletal muscle mass in kilograms measured by an InBody 770 body composition analyzer.	1 year
Visceral fat area	Visceral fat area in cm2 measured by an InBody 770 body composition analyzer.	1 year
Total body water	Total body water in liters measured by an InBody 770 body composition analyzer.	1 year

Collaborators and Investigators

• Sponsor: University of Pecs
• Investigators: Principal Investigator: Judit Bajor, MD, PhD, Division of Gastroenterology, First Department of Medicine, University of Pécs, 7624 Pécs, Hungary

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: September 4, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 18, 2025
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: cardiovascular risk; body composition; dietary intervention; coeliac disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Malabsorption Syndromes; Celiac Disease
• Other Study ID Numbers: 27521-5/2022/EÜIG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No