"Adding DNA-test for Screening of HLA-DQ2 and DQ8 to Improve Early Diagnosis of Celiac Disease"

NCT06179121 | Unknown DMC

• 2 other identifiers: P23.025 (METC LDD)05550402110016
• Study Type: observational
• Target: 508
• Locations: 1 country
• Sites: 1

Brief Summary

Celiac Disease (CD) is an immune-mediated systemic disorder elicited by the ingestion of gluten containing cereals from the normal diet, among others wheat, rye and barley. The disease is characterized by a variable combination of gluten-dependent clinical manifestations, CD specific antibodies, human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 haplotypes and chronic inflammation of the small bowel.CD is one of the most common lifelong food- related disorders; it has a frequency of 1% in the general population: this corresponds to 170.000 persons in the Netherlands, and of them at least 30.000 children. However, CD is frequently unrecognized, partially because of its variable clinical presentations and symptoms. That timely diagnosis and treatment of CD could be achieved by active case-finding, show the preliminary results of the ongoing ZonMw sponsored project GLUTENSCREEN (531002001; www.glutenscreen.nl). Currently, HLA-typing is not a part of GLUTENSCREEN because current technique presents important drawbacks in settings without the availability of a laboratory. We here propose to develop a novel test for DNA isolation for HLA typing extracted from the dried blood spots obtained from the POCT at the Preventive YHCCs for early detection of CD. Repeated testing for CD could be omitted in children tested HLA-DQ2/8 negative, this reflects to 60% of the targeted population. To embed this technique in the case finding setting at the YHCCs, the test will be offered to a significant part of the general Dutch population between 0-4 years old, since more than 95% of the general population visit the YHCC. Primary Objective: To validate the HLA-DQ typing in blood taken by a fingerprick; to make it feasible in the regular Preventive YHCCs organization. Study population: Phase 1: From 50 children attending the LUMC dept. of Pediatrics because of suspected CD in whom traditional HLA-typing is part of their standard of care or from children with diagnosed CD in whom their HLA typing is already known. Phase 2: All parents of symptomatic children, 1-4 years of age, who visit the Preventive YHCC in the region of Kennemerland, will be asked to participate in this study.

Conditions

Celiac Disease in Children

Keywords

Coeliac disease; Preventive Youth Health Care Center

Outcome Measures

Primary Outcomes (2)

• Sensitivity and specificity of the HLA-test in dried blood spots will be calculated (Phase 1)

  The results of the HLA-DQ2 and DQ8-typing using the dried blood spots will be compared with the results of the traditional HLA-typing. DNA extraction for HLA-DQ typing from dry blood spots will be performed using the QIAamp method \[12-15\]. A protocol to isolate DNA has been developed and the isolation is executable by all the well skilled laboratory analysts. DNA extraction per sample takes about 15 minutes and it is possible to determine several samples at the same time. The equipment and optical technology are already present at the LUMC.

  Month 6 to month 9 (total duration of the study: 18 months)

• Prevalence of HLA-DQ2/8 in the general population (Phase 2) population (parents) and the health care professionals.(Phase 2)

  Children with positive HLA-DQ2/8 typing (n/%), Children with negative HLA-DQ2/8 typing (n/%), Children in whom the test failed (including reason), Evaluation of the acceptance and impact of the HLA-typing for CD by the Dutchpopulation (parents) and the health care professionals For the HLA-DQ typing approximately 15 μL is necessary which corresponds with 1-2 droplets of blood. After informed consent, an extra droplet of blood will be collected for the novel HLA-DQ2/8 typing by the finger prick when performing the POCT for TGA determination as done in GLUTENSCREEN. The filter-papers will be stored, at room temperature, safely at the YHCCs. Once a week, all the collected filter papers with dried blood spots will be sent to the department of the Immunology in specially marked envelops. After the DNA isolation, HLA-DQ typing and interpretation.

  Month 9 to month 12 (after the validation phase 1)

Secondary Outcomes (1)

• Cost-effectiveness of the investigational strategy (Time investment by medical and nursing staff at the YHCCs (sec), costs of the investigational strategy (time, materials) (€))

  Month 9 to month 12

Study Arms (2)

Phase 1 Cohort (Validation of HLA- DQ2/8 typing)

Children (1-18 years old) coming for consultation at the LUMC for (suspicion of) CD

Other: DNA test for screening HLA-DQ2 and DQ8 from dried blood spots to early detect Celiac Disease

Phase 2 Cohort (Implementation of HLA-DQ2/8 typing on the Preventive YHCCs)

Children (12 months to 4 years old), at least with one of the 10 CD-related symptoms, not diagnosed with CD, and not on a GFD,

Other: DNA test for screening HLA-DQ2 and DQ8 from dried blood spots to early detect Celiac Disease

Interventions

DNA test for screening HLA-DQ2 and DQ8 from dried blood spots to early detect Celiac Disease OTHER

Phase 1 and 2: After blood collection (in combination with regular care) and informed consent, a blood droplet obtained by an additional fingerprick (Phase 1 and just an extra droplet from an existing finger prick for Phase 2) will be deposited on filter paper S\&S 903™ (Schleicher and Schuell). DNA will be isolated using the QIAamp method designated for this purpose from dried blood spots (Qiagen). The results of the HLA-DQ2 and DQ8-typing using the dried blood spots will be compared with the results of the traditional HLA-typing. Factors that may influence the quality of the material will be taken into account in the validation process.

Phase 1 Cohort (Validation of HLA- DQ2/8 typing); Phase 2 Cohort (Implementation of HLA-DQ2/8 typing on the Preventive YHCCs)

Eligibility Criteria

• Age: 12 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Phase 1: From 50 children attending the LUMC dept.of Pediatrics because of suspected CD in whom traditional HLA-typing is part of their standard of care or from children with diagnosed CD in whom their HLA typing is already known. The LUMC is a reference centre for CD in children. On the outpatient clinic, more than 90 children per 6 months will be seeing with (the suspicion) of CD and more than 500 children visit the clinic for the annual follow up of CD, which means that the number needed to validated the HLA-results are realistic. Phase 2 : All parents of symptomatic children, 1-4 years of age, who visit the Preventive YHCC in the region of Kennemerland, will be asked to participate in this study.

You may qualify if:

• Phase 1:
• age 1-18 years,
• consultation at the LUMC for (suspicion of) CD,
• parents have a sufficient knowledge of Dutch language,
• written informed consent from child and/or parent
• Phase 2:
• age 12 months to 4 years,
• at least one of the 10 CD-related symptoms
• not diagnosed with CD,
• not on a GFD,
• parents have a sufficient knowledge of Dutch language,
• written informed consent from the parent(s)

You may not qualify if:

• Phase 1 and 2:
• no informed consent,
• insufficient knowledge of Dutch language and/or inability to understand the information provided,
• bleeding disorders.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

Leiden University Medical Centre (LUMC)

Leiden, South Holland, 2333 ZA, Netherlands

Location

Related Publications (21)

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Biospecimen

Retention: SAMPLES WITH DNA

DNA acquired from dried blood samples

MeSH Terms

Conditions

Celiac Disease

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Caroline R Meijer-Boekel, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: December 12, 2023
• First Posted: December 21, 2023
• Study Start: September 1, 2022
• Primary Completion: May 1, 2024
• Study Completion: November 1, 2024
• Last Updated: December 21, 2023

Record last verified: 2023-12

Locations

NL (1)