Journal ReviewJournal ReviewLeah WendlandLeah WendlandDecember 3rd 2012December 3rd 2012

Prospective Study of Clinical and Prospective Study of Clinical and Histological Safety of Pure and Histological Safety of Pure and Uncontaminated Canadian Oats in the Uncontaminated Canadian Oats in the Management of Celiac Disease Management of Celiac Disease Michael Sai Lai Sey,MD: Jeremy Parfitt,MD,FRCPC: Jamie Michael Sai Lai Sey,MD: Jeremy Parfitt,MD,FRCPC: Jamie Gregor,MD,FRCPC Gregor,MD,FRCPC

ObjectivesObjectives

BackgroundBackground

ObjectiveObjective

MethodologyMethodology

ResultsResults

ConclusionConclusion

CritiqueCritique

Celiac Disease and OatsCeliac Disease and Oats

Cross-contamination was a major reason why Cross-contamination was a major reason why oats were considered unsafe in the pastoats were considered unsafe in the past

Oats, wheat and barley are usually grown Oats, wheat and barley are usually grown next to each other, processed in the same next to each other, processed in the same area, milled with the same equipment, and area, milled with the same equipment, and transported using the same containerstransported using the same containers

ObjectiveObjective

To assess the safety of oats manufactured To assess the safety of oats manufactured under the guidelines developed by the under the guidelines developed by the Canadian Celiac Association for individuals Canadian Celiac Association for individuals with celiac disease with celiac disease

GuidelinesGuidelines

Table 1. Canadian Celiac Association Guidelines for the Production of Pure Oats

Seed purity: Foundation #1 Canada Seed Act (≤1 wheat, barley, or rye seed per kg of oat groat)

Production: Dedicated fields, harvesting, processing, storage, and transportation equipment strictly for oats

Confirmation: Purity confirmed by R5 enzyme-linked immunosorbent assay, which is able to

detect ≥3 parts per million (ppm) gluten contamination (gluten-free diet ≤20 ppm)

MethodologyMethodology

INTENTION-TO-TREATANALYSIS

19 celiac patients considered• Asymptomatic• GFD 1 year• Normal tTG

4 patients declined

11 patientsstudy entryMod-MarshScore ≤ 1

10 patientscompliant withGFD

15 patients enrolled

PER-PROTOCOLANALYSIS

MethodologyMethodology

15 participants (Intention to Treat)15 participants (Intention to Treat)

CriteriaCriteria Asymptomatic on GF diet for at least a yearAsymptomatic on GF diet for at least a year Biopsy to confirm normal tissue Biopsy to confirm normal tissue

Transglutaminase (tTG) levelsTransglutaminase (tTG) levels

ExclusionExclusion Uncertain diagnosis of celiac disease (other Uncertain diagnosis of celiac disease (other

causes of villous atrophy)causes of villous atrophy) GFD non compliance, not in remissionGFD non compliance, not in remission

MethodologyMethodology

ProcessProcess Consume 350g pure uncontaminated oats per week Consume 350g pure uncontaminated oats per week

for 12 weeksfor 12 weeks Tested for gluten content using R5 enzyme-linked Tested for gluten content using R5 enzyme-linked

immunosorbent assasy (ELISA) immunosorbent assasy (ELISA) Premeasured bags of 12 (350g each)Premeasured bags of 12 (350g each) Donated by Cream Hill EstatesDonated by Cream Hill Estates

Record what was eaten 2 random times in 6 weeksRecord what was eaten 2 random times in 6 weeks Follow up at week 0, 6 and 12Follow up at week 0, 6 and 12

Assessed symptoms and serum testsAssessed symptoms and serum tests Continue GF dietContinue GF diet Biopsies obtained at week 0 and week 12Biopsies obtained at week 0 and week 12

BiopsiesBiopsies

Esophogastroduodenoscopy (EGD) was Esophogastroduodenoscopy (EGD) was conducted on each participantconducted on each participant

Biopsies were obtained at week 0 and week Biopsies were obtained at week 0 and week 1212

Taken from second part of the duodenumTaken from second part of the duodenum

Reviewed and scored by Dr. Parfitt using the Reviewed and scored by Dr. Parfitt using the Modified Marsh-Oberhuber classificationModified Marsh-Oberhuber classification

Modified Marsh ScoreModified Marsh Score

Table 2. Modified Marsh–Oberhuber Classification

Score IEL Crypts Villi0 <40 Normal Normal1 >40 Normal Normal2 >40 Hypertrophic Normal3a >40 Hypertrophic Mild atrophy3b >40 Hypertrophic Marked atrophy3c >40 Hypertrophic Absent

*IEL, intraepithelial lymphocytes, expressed as number ofIEL/100 epithelial cells.

ResultsResults

No symptomatic recurrencesNo symptomatic recurrences

No serological relapses in ITT or PPNo serological relapses in ITT or PP

2 cases of histological deterioration in ITT2 cases of histological deterioration in ITT 1 did not follow GF diet1 did not follow GF diet 1 progressed from Marsh 3a to 3b1 progressed from Marsh 3a to 3b

ConclusionConclusion

Supports safety of oats manufactured under Supports safety of oats manufactured under the Canadian Celiac Association guidelines for the Canadian Celiac Association guidelines for individuals with Celiac Diseaseindividuals with Celiac Disease

More studies need to be done to confirm this More studies need to be done to confirm this study due to the small sample size and the study due to the small sample size and the non-randomization, and un-blind studynon-randomization, and un-blind study

CritiqueCritique

LimitationsLimitations Small sample sizeSmall sample size No comparison groupNo comparison group Not blindNot blind Unclear how Unclear how

participants were participants were recruitedrecruited

Self reporting diariesSelf reporting diaries

PositivePositive Provided biopsies at the Provided biopsies at the

beginning and endbeginning and end Did not have Did not have

participants consume participants consume oats in excessoats in excess

Used Celiac Disease Used Celiac Disease Standard scoring for Standard scoring for biopsiesbiopsies

Thank You!Thank You!Questions?Questions?