Cardiovascular Risk Factors in Coeliac Disease: a Series of Studies

Overview

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.

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.

Interventions

• 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.
• Other 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.

Primary outcome measures

• Percent body fat [Time frame: 1 year]

Secondary outcome measures (12)

• Waist circumference [Time frame: 1 year]
• Blood pressure [Time frame: 1 year]
• Fatty liver disease [Time frame: 1 year]
• Cardiovascular risk assessment [Time frame: 1 year]
• Coeliac disease-related symptoms [Time frame: 1 year]
• Coeliac disease-specific quality of life [Time frame: 1 year]
• Disease activity [Time frame: 1 year]
• Sarcopenia [Time frame: 1 year]
• Triglyceride level [Time frame: 1 year]
• Cholesterol level [Time frame: 1 year]
• Fasting glucose level [Time frame: 1 year]
• Fasting insulin level [Time frame: 1 year]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

Hungary · 1 center

• First Department of Medicine, Medical School, University of Pécs — Pécs

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. PMID 10871564
• 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. PMID 26212198
• 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. PMID 28067892
• 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. PMID 31935859
• 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. PMID 30650530
• 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. PMID 31583132
• 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. PMID 22457854
• 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. PMID 32790023

Identifiers

NCT: NCT05530070 · 27521-5/2022/EÜIG

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗