Journal Review Leah Wendland December 3rd 2012

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

Objectives Background Background Objective Objective Methodology Methodology Results Results Conclusion Conclusion Critique Critique

Celiac Disease and Oats Cross-contamination was a major reason why oats were considered unsafe in the past Cross-contamination was a major reason why oats were considered unsafe in the past Oats, wheat and barley are usually grown next to each other, processed in the same area, milled with the same equipment, and transported using the same containers Oats, wheat and barley are usually grown next to each other, processed in the same area, milled with the same equipment, and transported using the same containers

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

Guidelines 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)

Methodology INTENTION-TO-TREAT ANALYSIS 19 celiac patients considered Asymptomatic GFD 1 year Normal tTG 4 patients declined 11 patients study entry Mod-Marsh Score ≤ 1 10 patients compliant with GFD 15 patients enrolled PER-PROTOCOL ANALYSIS     

Methodology 15 participants (Intention to Treat) 15 participants (Intention to Treat) Criteria Criteria Asymptomatic on GF diet for at least a year Asymptomatic on GF diet for at least a year Biopsy to confirm normal tissue Transglutaminase (tTG) levels Biopsy to confirm normal tissue Transglutaminase (tTG) levels Exclusion Exclusion Uncertain diagnosis of celiac disease (other causes of villous atrophy) Uncertain diagnosis of celiac disease (other causes of villous atrophy) GFD non compliance, not in remission GFD non compliance, not in remission

Methodology Process Process Consume 350g pure uncontaminated oats per week for 12 weeks Consume 350g pure uncontaminated oats per week for 12 weeks Tested for gluten content using R5 enzyme-linked immunosorbent assasy (ELISA) Tested for gluten content using R5 enzyme-linked immunosorbent assasy (ELISA) Premeasured bags of 12 (350g each) Premeasured bags of 12 (350g each) Donated by Cream Hill Estates Donated by Cream Hill Estates Record what was eaten 2 random times in 6 weeks Record what was eaten 2 random times in 6 weeks Follow up at week 0, 6 and 12 Follow up at week 0, 6 and 12 Assessed symptoms and serum tests Assessed symptoms and serum tests Continue GF diet Continue GF diet Biopsies obtained at week 0 and week 12 Biopsies obtained at week 0 and week 12

Biopsies Esophogastroduodenoscopy (EGD) was conducted on each participant Esophogastroduodenoscopy (EGD) was conducted on each participant Biopsies were obtained at week 0 and week 12 Biopsies were obtained at week 0 and week 12 Taken from second part of the duodenum Taken from second part of the duodenum Reviewed and scored by Dr. Parfitt using the Modified Marsh-Oberhuber classification Reviewed and scored by Dr. Parfitt using the Modified Marsh-Oberhuber classification

Modified Marsh Score Table 2. Modified Marsh–Oberhuber Classification Score IEL Crypts Villi 0 <40 Normal Normal 1 >40 Normal Normal 2 >40 Hypertrophic Normal 3a >40 Hypertrophic Mild atrophy 3b >40 Hypertrophic Marked atrophy 3c >40 Hypertrophic Absent *IEL, intraepithelial lymphocytes, expressed as number of IEL/100 epithelial cells.

Results No symptomatic recurrences No symptomatic recurrences No serological relapses in ITT or PP No serological relapses in ITT or PP 2 cases of histological deterioration in ITT 2 cases of histological deterioration in ITT 1 did not follow GF diet 1 did not follow GF diet 1 progressed from Marsh 3a to 3b 1 progressed from Marsh 3a to 3b

Conclusion Supports safety of oats manufactured under the Canadian Celiac Association guidelines for individuals with Celiac Disease Supports safety of oats manufactured under the Canadian Celiac Association guidelines for individuals with Celiac Disease More studies need to be done to confirm this study due to the small sample size and the non- randomization, and un-blind study More studies need to be done to confirm this study due to the small sample size and the non- randomization, and un-blind study

Critique Limitations Limitations Small sample size Small sample size No comparison group No comparison group Not blind Not blind Unclear how participants were recruited Unclear how participants were recruited Self reporting diaries Self reporting diaries Positive Positive Provided biopsies at the beginning and end Provided biopsies at the beginning and end Did not have participants consume oats in excess Did not have participants consume oats in excess Used Celiac Disease Standard scoring for biopsies Used Celiac Disease Standard scoring for biopsies

Thank You! Questions?