Safety of a new variety of barley for participants with coeliac disease

INTERVENTION: The study is a dietary intervention trial during which participants with coeliac disease will be randomly assigned to one of two treatment groups and will consume daily for 8 weeks a serve of either the ultra low gluten (ULG) barley or a gluten‐free (GF) control cereal. The amount of gluten ingested in the serve of ULG barley is about is 0.3mg; the amount of gluten in a sealed bag of cereal containing 11 serves is 3.3mg. Over the last 15 years CSIRO has developed barley varieties with nearly undetectable gluten levels. In the hull‐less variety we are examining in this clinical trial the level of gluten is so low (<5 ppm [parts per million]) that foods made exclusively from it would qualify as ‘gluten free’ under European and US international standards where foods containing less than 20 ppm gluten can carry that label. However in Australia due to the different legislative requirements foods here suitable for coeliac disease must be completely gluten free. A hulled variety of ULG barley is being cultivated commercially in Australia and used and sold in Germany in gluten‐free beer (http://www.pionier‐glutenfrei.de/). A healthy, high fibre grain safe for coeliacs and those avoiding gluten has significant potential to improve the diet of those individuals. This study involves scientific and clinical staff from CSIRO and Flinders Medical Centre (FMC) Department of Gastroenterology. Participants will be screened at FMC to ensure they are healthy and avoiding gluten, and will attend information sessions with a clinical trial co‐ordinator to discuss the study, and a research dietitian to explain the nutritional aspects of the study. Both these sessions will take about an hour each. During the first information session (and after consenting to participate) the participants will provide a blood sample which will be used to check they are generally healthy, and that their coeliac antibodies indicate they are not likely to be eating gluten. When the results are received from the laboratory the co‐ordinator will contact the participants and if they are eligible arrange the information session with the dietitian. During the second information session the dietitian will discuss the dietary aspects of the study, the faecal collections and provide a booklet of instructions. They will also arrange for a portable freezer, faecal collection kits, investigational product (including serving size instructions) and kitchen balance to be delivered to the participant's home. CONDITION: coeliac disease PRIMARY OUTCOME: Change in morphological assessment of the duodenal biopsies by analysis of stained slides by two specialist pathologists. This will provide measures of gluten‐related intestinal damage and inflammation. Changes in clinical symptoms as assessed by patient reported outcome measures (PROMs) questionnaires Coeliac disease specific serum antibody levels (IgA anti‐tissue transglutaminase (tTG) and anti‐deamidated gliadin peptide IgG antibodies). SECONDARY OUTCOME: Changes in faecal measures will determine the effects of ULG barley on digestive health and will include calculation of faecal bulk passed during 48 hour collections, short chain fatty acid concentrations, gluten immunogenic peptide levels, pH, moisture % and, if indicated, microbial analyses. Changes in faecal short chain fatty acid concentrations will determine the effects of ULG barley on digestive health Three day weighed food diaries will provide comprehensive details of the nutrient intakes of the participants INCLUSION CRITERIA: • Medically diagnosed coeliac disease (CD) • Have followed a GF diet for at least 2 years confirmed by history and normal CD serology (see exclusion criteria for normal range) from sample collected at screening visit • Males and females aged 18‐75 years Participants will be asked to eat their serve of investigational product at breakfast when it can be mixed with fruit/yoghurt/milk/other cereal. If an individual can not eat their whole serve at breakfast they can divide their serve and eat at two meals each day during the entire study. During the first week the participants are advised to gradually introduce the new cereal to their diet (instructions provided) to enable their gut and microbiome to adjust to the changes in their diet. The dietitian will advise participants how to substitute the investigational product for carbohydrate‐based foods containing similar amounts of energy to ensure weight changes for individuals during the study are under 2kg. When not consuming their investigational product the participants eat their normal, gluten free diet. On two occasions (V1, V2) participants will undergo an endoscopy to enable biopsy of the duodenum. This will be done before the dietary intervention starts (V1), and again at the end of the 8 week intervention (V2). These biopsies will enable the assessment by a pathologist of the health of the lining of their duodenum. Participants will make two 48 hr faecal collections during the study to enable the effects of the cereals on gut health to be assessed (before V1 and V2). Participants will complete questionnaires about any possible gluten ingestion during the study, and questionnaires to assess any symptoms they may experience. They will also complete a compliance diary and will return the empty plastic bags and uneaten investigational product at the end of the 8 week intervention. Participants will initially attend FMC for the two information sessions, and then either FMC or Noarlunga Hospitals on two occasions for their endoscopies. Participants will give blood (for coeliac disease serology and health screening) twice (first screening visit, and V2). Participants who complete the study will be given $200 vouchers to compensate for inconvenience and time the study required, and those who complete the first endoscopy will be provided a $50 voucher. Parking and reasonable travel costs will also be reimbursed. • No history of illness for the past 4 weeks which will affect their fitness for endoscopy, and any diarrhoeal illness • Understand the study and agree to participate • Are prepared to adhere to gluten free diet for the 12 weeks of the run‐in and study • Able to attend FMC (or Noarlunga Hospital) on 4 occasions during the study • Prepared to undergo 2 endoscopies • Willing to consume one serve of about 60g of investigational product daily for 8 weeks