## Protocol Section
### Identification Module
**NCT ID:** NCT03462979

**Brief Title:** Effects of Home Gluten Immunogenic Peptide Testing on Children With Celiac Disease

**Official Title:** GlPs Improve Practice (GIP) at Home: Effects of Home Gluten Immunogenic Peptide Testing on Children With Celiac Disease

#### Organization Study ID Info
**ID:** P00024698
#### Organization
**Class:** OTHER
**Full Name:** Boston Children's Hospital
### Status Module
#### Completion Date
**Date:** 2023-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-01-20

**Type:** ACTUAL

**Last Update Submit Date:** 2022-01-05

**Overall Status:** SUSPENDED

#### Primary Completion Date
**Date:** 2021-12-31

**Type:** ACTUAL

#### Start Date
**Date:** 2018-04-15

**Type:** ACTUAL

**Status Verified Date:** 2022-01

#### Study First Post Date
**Date:** 2018-03-13
**Type:** ACTUAL
**Study First Submit Date:** 2018-03-05
**Study First Submit QC Date:** 2018-03-09
**Why Stopped:** covid-19 pandemic
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** Glutenostics, LLC

#### Lead Sponsor

**Class:** OTHER

**Name:** Boston Children's Hospital

#### Responsible Party

**Investigator Affiliation:** Boston Children's Hospital

**Investigator Full Name:** Jocelyn Silvester

**Investigator Title:** Instructor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study aims to investigate how knowledge of gluten immunogenic peptide (GIP) levels in stool and urine affects subsequent adherence to a gluten-free diet. Half of the participants will receive results in real-time using a home device and the other half will store samples to be tested at the end of the 30 week study. Participants will also have a diet review with a dietitian at the beginning of the end of their study and be asked questions about their symptoms, gluten-free diet adherence and quality of life.

**Detailed Description:** Following a gluten-free diet is difficult. Eating small amounts of gluten may be common. Gluten may cause a wide range of symptoms, or no symptoms at all. Thus, there is not always a 'feedback loop' to alert to accidental gluten exposure. Nevertheless, these "silent" gluten exposures may interfere with recovery and healing of the intestine. New tools are available to test for fragments of gluten - Gluten Immunogenic Peptides (GIPs) in urine and stool.

The goal of this research study is to evaluate how knowledge of gluten-immunogenic peptide (GIP) levels in urine and stool affects subsequent adherence to a gluten-free diet. Participants will be children with celiac disease recruited at Boston Children's Hospital. All participants will undergo a diet assessment by a dietitian at the beginning and end of the study. At random intervals, participants will be prompted to collect their next urine sample and complete a survey related to symptoms and diet adherence. Half of the participants will store the sample to be tested later and the rest of the participants will be provided with devices to test their urine at home to receive immediate results. Participants in the home testing group will also be given a set of stool tests (x4) to use at their own discretion during the study period, and will report results and reasons for test use to the research team. GIP test results will be compared to other measures of celiac disease and gluten-free diet adherence, including antibody tests. These findings will help to determine how these new tools can be used to improve gluten-free diet adherence and symptoms and the effect on quality of life.

### Conditions Module

**Conditions:**

- Celiac Disease

- Gluten Sensitivity

- Gluten Enteropathy

- Gastrointestinal Disease

- Digestive System Disease

- Diet Modification

- Intestinal Disease

- Malabsorption Syndromes

- Patient Compliance

- Diagnostic Self Evaluation

- Quality of Life

**Keywords:**

- Gluten-free diet

- Urine

- Stool

- home testing

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** SUPPORTIVE_CARE

#### Enrollment Info

**Count:** 120

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants in the open results arm will be provided with Gluten Detective home testing kits (immunochromatographic lateral flow tests) at week 8 of the study for immediate qualitative (yes/no) feedback about the presence of biomarkers of gluten in their stool and/or urine. During the period from week 8 to week 30, participants will be contacted a total of 6 times at random intervals to collect and test urine samples and complete a questionnaire.Additionally, participants will be given 4 stool test kits, with instructions that they may use these at times of their choosing and will report results and reasons for test use, if any. During this time participants will also keep a diary of suspected gluten exposures. All samples collected will be returned during the week 30 study visit.

**Intervention Names:**

- Device: Immunochromatographic lateral flow test

**Label:** Open Results with home testing

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants in the blinded arms will not be given a test kit but will be given sample collection materials. During the period from week 8 to week 30 of the study, participants will be contacted a total of 6 times at random intervals, instructed to collect urine samples, and complete a questionnaire. Participants will also keep a diary of suspected gluten exposures. All samples collected will be returned during the week 30 study visit. After completion of sample collection, all participants will be unblinded and notified of the results once the samples have been processed.

**Label:** Blinded (sample collection only)

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Open Results with home testing

**Description:** The immunochromatographic lateral flow test (Gluten Detective) is an at-home test that detects gluten immunogenic peptides excreted in stool or urine. This test can detect gluten exposures which occurred either during the last 24 hours (urine) or within up to a 7 day window (stool). Minimum intake amounts of gluten for successful detection using these test are 50mg (stool) to 500mg (urine)

**Name:** Immunochromatographic lateral flow test

**Other Names:**

- Gluten Detective

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Gluten exposure frequency is defined as the average per individual subject post-randomization percentage of samples collected between weeks 8 and 30 with detectable gluten immunogenic peptides using the qualitative assay (Gluten Detective)

**Measure:** Difference in frequency of gluten exposure in open results vs blinded groups following randomization.

**Time Frame:** Weeks 8 to 30

#### Secondary Outcomes

**Description:** Mean gluten exposure is defined as the average per individual subject post-randomization concentration of gluten immunogenic peptides detected using the quantitative assay

**Measure:** Difference in quantity of mean gluten exposure following randomization in blinded vs. open results groups

**Time Frame:** weeks 8 - 30

**Description:** Symptom score (using the Celiac Disease PedsRO or ObsRO as appropriate for age) at week 30

**Measure:** Celiac disease symptom score in blinded vs. open results group at the end of the study

**Time Frame:** Week 30

**Description:** Symptom score (using the Celiac Disease PedsRO or ObsRO as appropriate) and the change in symptom score between the end of the run-in period (week 8) and the end of the study period (week 30) will be calculated arithmetically.

**Measure:** Change in symptom score in blinded vs. open results group

**Time Frame:** weeks 8 and 30

**Description:** The CDDUX is a disease specific quality of life instrument for children with celiac disease.

**Measure:** Change in celiac disease specific quality of life as measured by Celiac Disease DUX (CDDUX) in blinded vs. open results groups

**Time Frame:** weeks 8 and 30

**Description:** The PedsQL 4.0 Generic Core is a validated pediatric general quality of life measure that is caregiver reported for younger children and both child and caregiver reported for older children. The score is scaled from 0 (lowest) to 100 (highest) with higher scores corresponding to better health related quality of life.

**Measure:** Change in pediatric health related quality of life as measured by PedsQL 4.0 generic core scale in blinded vs. open results groups

**Time Frame:** weeks 8 and 30

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Age 6 to 18 years at study entry
* Diagnosis of celiac disease based upon either

  1. Biopsy criteria i) Marsh 3 lesion and/or villous height:crypt depth ratio (Vh:Cd) \< 3 with intraepithelial lymphocytosis; and ii) Elevated serum tTG IgA and/or EMA antibodies
  2. Serologic/genetic (ESPGHAN 2012) criteria i) Symptoms compatible with celiac disease; ii) Serum tTG IgA \> 10 x upper limit of normal for assay; iii) EMA titre elevated on a separate sample; and iv) HLADQ genotype compatible with celiac disease.
* Adherence to a gluten-restricted diet (self-reported) for 6 months or more
* Attending a clinician assessment for celiac disease at Boston Children's Hospital

Exclusion Criteria:

* Unable to provide urine and/or stool sample or attend study visits
* English proficiency unsuitable for completion of surveys
* Anuria or oliguria
* Reliance upon commercial gluten-free formulas as primary source of nutrition
* Comorbid condition that in the opinion of the investigator would interfere with the subject's participation in the study or would confound the results of the study

**Maximum Age:** 18 Years

**Minimum Age:** 6 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Boston

**Country:** United States

**Facility:** Boston Children's Hospital

**State:** Massachusetts

**Zip:** 02115

#### Overall Officials

**Official 1:**

**Affiliation:** Boston Children's Hospital, Beth Israel Deaconess Medical Center

**Name:** Jocelyn A Silvester, MD PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Moreno ML, Cebolla A, Munoz-Suano A, Carrillo-Carrion C, Comino I, Pizarro A, Leon F, Rodriguez-Herrera A, Sousa C. Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing. Gut. 2017 Feb;66(2):250-257. doi: 10.1136/gutjnl-2015-310148. Epub 2015 Nov 25.

**PMID:** 26608460

**Citation:** Comino I, Real A, Vivas S, Siglez MA, Caminero A, Nistal E, Casqueiro J, Rodriguez-Herrera A, Cebolla A, Sousa C. Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces. Am J Clin Nutr. 2012 Mar;95(3):670-7. doi: 10.3945/ajcn.111.026708. Epub 2012 Jan 18.

**PMID:** 22258271

**Citation:** Comino I, Fernandez-Banares F, Esteve M, Ortigosa L, Castillejo G, Fambuena B, Ribes-Koninckx C, Sierra C, Rodriguez-Herrera A, Salazar JC, Caunedo A, Marugan-Miguelsanz JM, Garrote JA, Vivas S, Lo Iacono O, Nunez A, Vaquero L, Vegas AM, Crespo L, Fernandez-Salazar L, Arranz E, Jimenez-Garcia VA, Antonio Montes-Cano M, Espin B, Galera A, Valverde J, Giron FJ, Bolonio M, Millan A, Cerezo FM, Guajardo C, Alberto JR, Rosinach M, Segura V, Leon F, Marinich J, Munoz-Suano A, Romero-Gomez M, Cebolla A, Sousa C. Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients. Am J Gastroenterol. 2016 Oct;111(10):1456-1465. doi: 10.1038/ajg.2016.439. Epub 2016 Sep 20. Erratum In: Am J Gastroenterol. 2017 Jul;112(7):1208.

**PMID:** 27644734

**Citation:** Shan L, Molberg O, Parrot I, Hausch F, Filiz F, Gray GM, Sollid LM, Khosla C. Structural basis for gluten intolerance in celiac sprue. Science. 2002 Sep 27;297(5590):2275-9. doi: 10.1126/science.1074129.

**PMID:** 12351792

**Citation:** Moron B, Bethune MT, Comino I, Manyani H, Ferragud M, Lopez MC, Cebolla A, Khosla C, Sousa C. Toward the assessment of food toxicity for celiac patients: characterization of monoclonal antibodies to a main immunogenic gluten peptide. PLoS One. 2008 May 28;3(5):e2294. doi: 10.1371/journal.pone.0002294.

**PMID:** 18509534

**Citation:** van Doorn RK, Winkler LM, Zwinderman KH, Mearin ML, Koopman HM. CDDUX: a disease-specific health-related quality-of-life questionnaire for children with celiac disease. J Pediatr Gastroenterol Nutr. 2008 Aug;47(2):147-52. doi: 10.1097/MPG.0b013e31815ef87d.

**PMID:** 18664865

**Citation:** Varni JW, Burwinkle TM, Seid M. The PedsQL 4.0 as a school population health measure: feasibility, reliability, and validity. Qual Life Res. 2006 Mar;15(2):203-15. doi: 10.1007/s11136-005-1388-z.

**PMID:** 16468077

**Citation:** Silvester JA, Graff LA, Rigaux L, Walker JR, Duerksen DR. Symptomatic suspected gluten exposure is common among patients with coeliac disease on a gluten-free diet. Aliment Pharmacol Ther. 2016 Sep;44(6):612-9. doi: 10.1111/apt.13725. Epub 2016 Jul 22.

**PMID:** 27443825

**Citation:** Lebwohl B, Sanders DS, Green PHR. Coeliac disease. Lancet. 2018 Jan 6;391(10115):70-81. doi: 10.1016/S0140-6736(17)31796-8. Epub 2017 Jul 28.

**PMID:** 28760445

**Citation:** Ludvigsson JF, Ciacci C, Green PH, Kaukinen K, Korponay-Szabo IR, Kurppa K, Murray JA, Lundin KEA, Maki MJ, Popp A, Reilly NR, Rodriguez-Herrera A, Sanders DS, Schuppan D, Sleet S, Taavela J, Voorhees K, Walker MM, Leffler DA. Outcome measures in coeliac disease trials: the Tampere recommendations. Gut. 2018 Aug;67(8):1410-1424. doi: 10.1136/gutjnl-2017-314853. Epub 2018 Feb 13.

**PMID:** 29440464

## Document Section

### Large Document Module

#### Large Docs

- Date: 2019-04-30

- Filename: Prot_004.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: False

- Label: Study Protocol

- Size: 406820

- Type Abbrev: Prot

- Upload Date: 2019-06-04T12:18

- Date: 2020-03-26

- Filename: ICF_006.pdf

- Has ICF: True

- Has Protocol: False

- Has SAP: False

- Label: Informed Consent Form

- Size: 662677

- Type Abbrev: ICF

- Upload Date: 2020-04-10T08:56

## Annotation Section

### Unposted Annotation

#### Event: RELEASE

- Date: 2022-06-22

- Date Unknown: Unknown

#### Event: RESET

- Date: 2023-03-31

- Date Unknown: Unknown

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000008659

- Term: Metabolic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

### Condition Browse Module - Browse Leaves

- ID: M10018

- Name: Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: HIGH

- As Found: Intestinal Diseases

- ID: M7255

- Name: Digestive System Diseases

- Relevance: HIGH

- As Found: Digestive System Diseases

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: HIGH

- As Found: Gastrointestinal Diseases

- ID: M5696

- Name: Celiac Disease

- Relevance: HIGH

- As Found: Celiac Disease

- ID: M11278

- Name: Malabsorption Syndromes

- Relevance: HIGH

- As Found: Malabsorption Syndromes

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T6034

- Name: Quality of Life

- Relevance: HIGH

- As Found: Quality of Life

### Condition Browse Module - Meshes

- ID: D000002446

- Term: Celiac Disease

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000008286

- Term: Malabsorption Syndromes

### Misc Info Module

#### Submission Tracking

- Estimated Results First Submit Date: 2022-06-22

##### Submission Infos

- MCP Release N: Unknown

- Release Date: 2022-06-22

- Reset Date: 2023-03-31

- Unrelease Date: Unknown

- Unrelease Date Unknown: Unknown

- Version Holder: 2024-05-24
