Lymphocytic Enteritis and Suspected Coeliac Disease: Gluten vs Placebo

NCT02472704 | Completed DMC

• 1 other identifier: DSG-DC/01/01
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

Patients with lymphocytic enteritis (LE), HLA-DQ2/8+, negative celiac serology and clinical and histological response to a gluten-free diet (GFD) do not fulfil the diagnostic criteria of coeliac disease (CoD). At present it remains unclear whether they suffer from coeliac gluten sensitivity (CGS) or non-coeliac gluten sensitivity (NCGS). There are specific tissue markers of CoD such as anti-transglutaminase deposits (tTG) and intraepithelial lymphocytes expressing T-cell receptor (TCR) gamma/delta+. Aim: To demonstrate the existence of CGS in these patients despite having negative celiac serology. Methods: Double-blind randomized clinical trial of gluten vs placebo rechallenge for 6 months in patients with LE on a GFD. Inclusion criteria: \>18 years, initial presentation with GI symptoms, HLA-DQ2/8+, negative celiac serology, good clinical and histological response to GFD. Patients were randomised to gluten (20 g/day) and placebo (maltrodextrin) (identical powder sachets mixed with meals). Clinical symptoms were analysed using visual analogue scales. Quality of life (GIQLI), adherence to diet, serology, and histological changes including gamma/delta+ IEL and tTG deposits were evaluated.

Conditions

Celiac Disease; Non-celiac Gluten Sensitivity

Keywords

celiac disease; lymphocytic enteritis; non-celiac gluten sensitivity; double-blind gluten rechallenge

Outcome Measures

Primary Outcomes (1)

• Clinical relapse

  Visual analogue scale on clinical symptoms at each visit (Baseline, 4 weeks, 12 weeks, 24 weeks)

  6 months

Secondary Outcomes (4)

• Changes in health related quality of life

  Change from baseline at 6 months (or premature withdrawn)

• Histological evolution (Changes in intraepithelial lymphocyte count)

  Changes from baseline at 6 months (or premature withdrawn)

• Changes in gamma/delta cells

  Changes from baseline at 6 months (or premature withdrawn)

• Changes in transglutaminase deposits

  Changes from baseline at 6 months (or premature withdrawn)

Study Arms (2)

Gluten challenge

ACTIVE COMPARATOR

Gluten powder (10 g every 12 hours), 24 weeks

Dietary Supplement: Gluten challenge

Placebo challenge

PLACEBO COMPARATOR

Placebo (maltodextrin; 10 g every 12 hours), 24 weeks

Dietary Supplement: Placebo challenge

Interventions

Gluten challenge DIETARY_SUPPLEMENT

gluten (20 g/day) (identical powder sachets than placebo, mixed with meals) rechallenge while on a gluten-free diet

Gluten challenge

Placebo challenge DIETARY_SUPPLEMENT

placebo (maltrodextrin) (identical powder sachets than gluten, mixed with meals) rechallenge while on a gluten-free diet

Placebo challenge

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Giving written informed consent
• Patients with age ≥18 years
• Histological diagnosis confirmed of lymphocytic enteritis (LE)
• Celiac genetic study (HLA-DQ2 and /or HLA-DQ8 positive)
• Negative serology of celiac disease
• Previous complete clinical and histological response to gluten-free diet
• Initial (at diagnosis) GI symptoms with or without extraintestinal manifestations.
• No previous studies on both IEL cytometric pattern and anti-TG2 IgA subepithelial deposits.

You may not qualify if:

• Patients who are unable to adhere to the study visit schedule and other protocol requirements according to the investigator.
• Participation in a clinical trial in the last 30 days, simultaneous participation in a trial or prior participation in this study.
• Previous diagnosis with gluten-sensitive enteropathy with villous atrophy and positive serology.
• Severe co-morbidities.
• Drug or alcohol abuse.
• Pregnancy or breast-feeding.
• At the initial diagnosis, other LE aetiologies, like non-steroidal anti-inflammatory drugs intake, parasitic infection, and Helicobacter pylori infection, were appropriately ruled out.

Sponsors & Collaborators

• Hospital Mutua de Terrassa: lead

Related Publications (4)

• Molina-Infante J, Santolaria S, Sanders DS, Fernandez-Banares F. Systematic review: noncoeliac gluten sensitivity. Aliment Pharmacol Ther. 2015 May;41(9):807-20. doi: 10.1111/apt.13155. Epub 2015 Mar 6.

  PMID: 25753138 BACKGROUND

• Fernandez-Banares F, Carrasco A, Garcia-Puig R, Rosinach M, Gonzalez C, Alsina M, Loras C, Salas A, Viver JM, Esteve M. Intestinal intraepithelial lymphocyte cytometric pattern is more accurate than subepithelial deposits of anti-tissue transglutaminase IgA for the diagnosis of celiac disease in lymphocytic enteritis. PLoS One. 2014 Jul 10;9(7):e101249. doi: 10.1371/journal.pone.0101249. eCollection 2014.

  PMID: 25010214 BACKGROUND

• Rosinach M, Esteve M, Gonzalez C, Temino R, Marine M, Monzon H, Sainz E, Loras C, Espinos JC, Forne M, Viver JM, Salas A, Fernandez-Banares F. Lymphocytic duodenosis: aetiology and long-term response to specific treatment. Dig Liver Dis. 2012 Aug;44(8):643-8. doi: 10.1016/j.dld.2012.03.006. Epub 2012 Apr 11.

  PMID: 22497904 BACKGROUND

• Rosinach M, Fernandez-Banares F, Carrasco A, Ibarra M, Temino R, Salas A, Esteve M. Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease. PLoS One. 2016 Jul 8;11(7):e0157879. doi: 10.1371/journal.pone.0157879. eCollection 2016.

  PMID: 27392045 DERIVED

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

• Fernando Fernández-Bañares, MD

  Hospital Mutua Terrassa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: June 9, 2015
• First Posted: June 16, 2015
• Study Start: September 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 16, 2015

Record last verified: 2015-06