Clinical Trial: Lymphocytic Enteritis and Suspected Coeliac Disease: Gluten vs Placebo

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Lymphocytic Enteritis and Suspected Coeliac Disease: Double-blind Gluten vs Placebo Rechallenge

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.


Detailed Summary:

Duodenal intraepithelial lymphocytosis (lymphocytic enteritis, LE) is defined by normal villous architecture and intraepithelial lymphocytes (IEL) >25/100 enterocytes. It is a frequent finding present in 2% to 5,4% of duodenal biopsies.

LE is secondary to coeliac disease (CoD) in only a minority of patients, since it may be a response to other inflammatory processes in the gut. Other possible aetiologies of LE include infections (Helicobacter Pylori), drugs (nonsteroidal anti-inflammatory or acetylsalicylic acid) and autoimmune disease. Observational studies have established CoD to account for 10% to 43% of cases with LD and positive HLA-DQ2/8 after undertaking an exhaustive diagnostic work-up. These 'minor' forms of CoD may have similar clinical manifestations to those with villous atrophy.

However, these patients with 'minor' CoD have often negative celiac serology, and then do not fulfil the present criteria to diagnose CoD. In fact, using the present diagnostic criteria they should be included in the definition of non-celiac gluten sensitivity (NCGS). For diagnosing NCGS it is necessary to rule out CoD by means of negative serology -endomysial and tissue transglutaminase IgA antibodies- and a duodenal biopsy with absence of villous atrophy on a gluten-containing diet. As such it is accepted that NCGS patients might have LE. A recent systematic review on NCGS revealed that 44% of patients presented HLA-DQ2/8 haplotypes, suggesting that a subgroup of patients with NCGS may actually belong in the spectrum of CoD, which some authors have so-called 'coeliac lite' disease.

The gold-standard assay for confirming NCGS requires dietary elimination, followed by double-blind, randomized, placebo-controlled food challenge. This procedure is difficult to adopt routinely in clinic
Sponsor: Hospital Mutua de Terrassa

Current Primary Outcome: Clinical relapse [ Time Frame: 6 months ]

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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Changes in health related quality of life [ Time Frame: Change from baseline at 6 months (or premature withdrawn) ]
    GI quality of life index (GIQLI) at basal and 24 week visits
  • Histological evolution (Changes in intraepithelial lymphocyte count) [ Time Frame: Changes from baseline at 6 months (or premature withdrawn) ]
    Changes in intraepithelial lymphocyte count
  • Changes in gamma/delta cells [ Time Frame: Changes from baseline at 6 months (or premature withdrawn) ]
    Changes in cytometric count of gamma/delta cells
  • Changes in transglutaminase deposits [ Time Frame: Changes from baseline at 6 months (or premature withdrawn) ]
    Presence of tTG deposits (IF)


Original Secondary Outcome: Same as current

Information By: Hospital Mutua de Terrassa

Dates:
Date Received: June 9, 2015
Date Started: September 2011
Date Completion:
Last Updated: June 15, 2015
Last Verified: June 2015