Clinical trial NCT05530070: Cardiovascular Risk Factors in Coeliac Disease: a Series of Studies
Official title: Cardiovascular Risk Factors in Coeliac Disease: a Series of Studies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coeliac Disease
Keywords: coeliac disease
cardiovascular risk
body composition
dietary intervention
Lead sponsor: University of Pecs
Sponsor class: OTHER
First posted: 2022-09-07
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial is a series of three multicentric studies. It includes 1) a case-control study, which compares newly diagnosed CD patients (n=37) and CD patients on a GFD (n=99) to matched non-coeliac control subjects (n=136); 2) a prospective cohort study, which investigates how the outcomes change during a 1-year GFD started after diagnosis of CD (n=236); 3) an RCT, which investigates how a dietetic intervention (n=95) influences the outcomes, compared to standard of care (n=95), in CD patients following a strict GFD for at least 1 year. There will be no intervention for the sake of the study in the case-control and the cohort study. Parameters of interest will be assessed only once in the case-control study and twice in the cohort study. In the RCT, randomization will be carried out after the baseline dietary education and interview, in 1:1 allocation ratio. Parameters will be recorded at baseline and the end of the study.
Primary purpose: PREVENTION

Brief 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.

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.

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.

Primary outcomes:
measure: Percent body fat
timeFrame: 1 year
Secondary outcomes:
measure: Waist circumference
timeFrame: 1 year
measure: Blood pressure
timeFrame: 1 year
measure: Fatty liver disease
timeFrame: 1 year
measure: Cardiovascular risk assessment
timeFrame: 1 year
measure: Coeliac disease-related symptoms
timeFrame: 1 year
measure: Coeliac disease-specific quality of life
timeFrame: 1 year
measure: Disease activity
timeFrame: 1 year
measure: Sarcopenia
timeFrame: 1 year
measure: Triglyceride level
timeFrame: 1 year
measure: Cholesterol level
timeFrame: 1 year
measure: Fasting glucose level
timeFrame: 1 year
measure: Fasting insulin level
timeFrame: 1 year
measure: Haemoglobin (Hb) A1c level
timeFrame: 1 year
measure: Homeostasis Model Assessment (HOMA) index
timeFrame: 1 year
measure: Bilirubin level
timeFrame: 1 year
measure: Uric acid level
timeFrame: 1 year
measure: Urea level
timeFrame: 1 year
measure: Creatinine level
timeFrame: 1 year
measure: Sodium level
timeFrame: 1 year
measure: Potassium level
timeFrame: 1 year
measure: Calcium level
timeFrame: 1 year
measure: Vitamin D
timeFrame: 1 year
measure: Vitamin B12
timeFrame: 1 year
measure: Folic acid level
timeFrame: 1 year
measure: Iron level
timeFrame: 1 year
measure: Ferritin level
timeFrame: 1 year
measure: Transferrin level
timeFrame: 1 year
measure: Transferrin saturation
timeFrame: 1 year
measure: International Normalized Ratio (INR)
timeFrame: 1 year
measure: Aspartate aminotransferase level
timeFrame: 1 year
measure: Alanine aminotransferase level
timeFrame: 1 year
measure: Fibrosis-4 (FIB-4) Index
timeFrame: 1 year
measure: Total protein level
timeFrame: 1 year
measure: Albumin level
timeFrame: 1 year
measure: Immunoglobulins
timeFrame: 1 year
measure: High-sensitivity C-reactive protein (hs-CRP) level
timeFrame: 1 year
measure: Fibrinogen level
timeFrame: 1 year
measure: Blood counts
timeFrame: 1 year
measure: Homocysteine levels
timeFrame: 1 year
measure: Interleukin-6 levels
timeFrame: 1 year
measure: Leptin levels
timeFrame: 1 year
measure: Ghrelin levels
timeFrame: 1 year
measure: Adiponectin levels
timeFrame: 1 year
measure: Galectin-3 levels
timeFrame: 1 year
measure: Dietary interview
timeFrame: 1 year
measure: Celiac Disease Adherence Test
timeFrame: 1 year
measure: Coeliac-specific antibodies
timeFrame: 1 year
measure: Urine gluten immunogenic peptide
timeFrame: 1 year
measure: Diet composition
timeFrame: 1 year
measure: Body height
timeFrame: 1 year
measure: Body weight
timeFrame: 1 year
measure: Body mass index
timeFrame: 1 year
measure: Body fat mass
timeFrame: 1 year
measure: Skeletal muscle mass
timeFrame: 1 year
measure: Visceral fat area
timeFrame: 1 year
measure: Total body water
timeFrame: 1 year
Other outcomes:
Locations:
city: Pécs
country: Hungary
facility: First Department of Medicine, Medical School, University of Pécs
state: Baranya
Study officials:
affiliation: Division of Gastroenterology, First Department of Medicine, University of Pécs, 7624 Pécs, Hungary
name: Judit Bajor, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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.
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.
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.
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.
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.