Dietary Intervention for Eczema

This RCT is a two-arm intervention study design: Arm 1. (i) dietary intervention, involving removal of three common food allergens (egg, dairy and wheat), and reduction of dietary salicylates (with each eligible food item containing less than or equal to 0.25 mg/g of free and bound salicylic acid), and histamine, with set menu and recipes, and appropriate supplementation (2 x powdered supplements including calcium) to fill nutritional gaps for 6 weeks, or Arm2. (ii) the control group who receive a sham consultation with standard care at baseline, then remain on their habitual diet with no new treatment for 6 weeks. There are four phases of the trial: Phase 1: Eighty adults with moderate-to-severe atopic dermatitis are monitored for 2 weeks with no intervention, serving as their own control. All participants record their habitual diet for three days via Photographic Food Record so water and nutrient intakes (Ca, Fe, Zn, K, Na, retinol equivalents, and vitamins C, D and E) can be compared to Australian Estimated Average Requirement (EAR) guidelines. At -2 weeks, participants attend Bond University for in-person assessment. All other contact during phase one occurs remotely via email or phone call. Phase 2: The dietary intervention has two arms with parallel groups containing 40 participants in the intervention group and 40 participants in the control group (with an anticipated 20% drop out) At baseline, both groups will take part in a sham consultation at Bond University, involving standard care, assessment of skin using the Eczema Severity Score Index (EASI), itch score, and quality of life, measured by the Dermatology Life Quality Index (DLQI). Weight is recorded using scales. Standard care is defined by the management flowchart published by Smith S, et al. (2020) and researchers conducting the sham consultation will be trained by a specialist dermatologist. On exiting the consultation, individuals will be taken to a room on a different floor where an independent researcher will provide a concealed manual (identified only with individual ID) containing instructions on standard care for the control group and a concealed manual containing the diet intervention for the participants. The participants are randomised to 6 weeks of either (i) dietary intervention, involving removal of three common food allergens (egg, dairy and wheat), and reduction of dietary salicylates (with each eligible food item containing less than or equal to 0.25 mg/g of free and bound salicylic acid), and histamine, with set menu and recipes, and appropriate supplementation (2 x powdered supplements including calcium) to fill nutritional gaps for 6 weeks, or (ii) the control group who receive a sham consultation with standard care at baseline, then remain on their habitual diet with no new treatment for 6 weeks. Phase 3: In week 6, all subjects attend in person at Bond University (which is within a 1-kilometre radius from Robina Hospital) to assess quality of life (DLQI), disease severity (EASI) and Itch Score, and feasibility and acceptability of the diet using a series of questionnaires. Week 6 also includes Oral Food Challenge involving salicylates for both groups; week 7, histamine challenge; and week 8, milk/egg/wheat challenge, followed by 2-h monitoring with a nurse present. If a participant does not react within 2 hours after oral challenge on site at Bond University, follow up by researchers will occur 24-h and 48-h later (remotely, via email and phone). Follow up involves the participant taking photos of their skin (holding a colour chart beside their skin) at 24-hr and 48-hr after oral challenge for assessment, and then emailing the images to the researchers. Phase 4: 3-month follow up where participants are asked via email a series of questions including ongoing adherence to the diet. They are asked to provide images of their skin (using a colour card) for EASI skin assessment. Materials, procedures and processes: Pre-screening Eligibility Survey will be sent to all interested participants during pre-trial initial screening; consent forms for participants and controls; measuring tape to be used during taking of EASI assessment images to be used by researchers; EASI training information for researchers; training instructions for Research Food Diary app for researchers and participants; instructions by Bird et al. (2020) for oral challenge (for researchers); participant manual (including instructions, menus and recipes) for FISHA intervention participants; standard care manual for the control group; Food Skills Video for participants to enhance their cooking skills; instructional videos for the preparation of 10-15 recipes; Oral Challenge Consent Forms for all participants in the trial who elect to complete the oral challenge involving salicylates, histamine, egg, milk and wheat; scales to measure weight of all participants; and blood vials, needles, and medical gloves for collecting blood samples. The Australian EAR will be used for assessing nutrient intakes of groups at baseline and week 4. Where EARs are not available, Adequate Intakes (AI) will be used as a benchmark. The intervention, designed and reviewed by a multidisciplinary team including a qualified nutritionist and dietitian, adheres to Australian Dietary Guidelines, with EAR guidelines used to determine the nutritional needs of participants are met. The intervention will be delivered by the following: a qualified nutritionist with 22 years of clinical experience working with patients with atopic dermatitis and food intolerance including personalised dietary interventions and recipe/menu creation; clinical trial specialist with over 15 years of experience in academic research including managing large scale, complex clinical trials including dietary intervention studies; biostatistician with more than 20 years of experience. Validated tool, Eczema Area and Severity Index (EASI) will be used for skin assessment to measure atopic dermatitis severity (-2 weeks, baseline, week 6, 7 and 8 and follow-up). Researchers will be trained by local dermatologist in performing skin assessments using EASI. Images will be taken to assist with accurate assessment of atopic dermatitis severity. Eligible participants will have an EASI score between 7.1 to 72.0 (moderate to very severe atopic dermatitis). The minimal clinically important difference is 6.6 EASI points (Schram et al., 2012) so treatment success is a reduction in EASI score by 6.6 points or more. Treatment failure for a participant is defined as inadequate improvement of atopic dermatitis as shown by EASI (less than 6.5-point reduction or an increase in score), or severe adverse event/s, or poor tolerability of the intervention from week 4. Participants allocated to the diet intervention will be provided with two free compounded powder vitamin and mineral supplements (including calcium as the intervention omits dairy), and approximately 15 pantry items including olive oil and wheat-free oats. Weekly phone calls and text message reminders and check-ins will help to ensure participants stay on track. Weekly online meetings also provide an opportunity to ask questions or report concerns. At baseline participants will be emailed a link to an online 20-minute Food Skills Video for skill development on food purchase and food preparation, allowing people with low cooking skills to participate in the trial. Researchers will call participants on day 1 to check if they can access the videos and to answer any questions or concerns. Adherence is monitored by weekly Photographic Food Records, weekly Zoom/Teams/phone meetings, and face-to-face meetings (weeks 0, 4 and 6). Blood collection: A trained phlebotomist will collect overnight fasted blood samples via venipuncture at baseline and 6 weeks during intervention to assess circulating proteins by targeted proteomics (Harney 2019). The volume of blood collected will be less than or equal to 20ml. Blood samples will be processed and plasma stored at -80degCel to maintain sample integrity for subsequent analysis. After a 12-month study intervention period, the intervention and control groups will be compared, following this the control group will receive the dietary intervention as a benefit for participation in the study, but they will not be followed up for assessment of outcomes within this study. References Bird JA, Leonard S, Groetch M, et al. Conducting an Oral Food Challenge: An Update to the 2009 Adverse Reactions to Foods Committee Work Group Report. J Allergy Clin Immunol Pract. Jan 2020;8(1):75-90 e17 Smith S, Baker C, Gebauer K, et al. Atopic dermatitis in adults: An Australian management consensus. Australas J Dermatol. Feb 2020;61(1):23-32. Harney DJ, Hutchison AT, Su Z, Hatchwell L, Heilbronn LK, Hocking S, et al. Small-protein Enrichment Assay Enables the Rapid, Unbiased Analysis of Over 100 Low Abundance Factors from Human Plasma. Mol Cell Proteomics. 2019;18(9):1899-915.