Investigating the effect of oral insulin on glycaemia

The proposed pilot study aims to provide preliminary data of whether oral insulin is acceptable and can be used as an adjunct therapeutic intervention in individuals with Type 1 diabetes (T1D), and to use the information obtained to inform a future randomised controlled trial specifically designed to assess the efficacy of oral insulin as an adjunct to current insulin therapy. The proposed pilot study is a prospective, 12-week, single-arm study in 10 adolescents/adults with T1D in Western Australia. All assessments and drug administration will be carried out by an experience clinical diabetes research nurse and a paediatric endocrinologist. The study will be supervised by the principal investigator or associate investigator, both being practising paediatric endocrinologists. The oral insulin capsule used in this study, CapsulinTM, has been developed by Diabetology Ltd and is based on their patented Axcess delivery system. Capsulin is an enteric-coated capsule which contains unmodified human recombinant insulin with a mixture of well-characterized and “generally regarded as safe” (GRAS) substances which facilitate the transport of insulin through the intestinal wall and into the portal circulation. The capsule is stable at room temperature for 18 months. Capsulin comes in 150 IU dose capsules, and will be provided to the participants in bottles fitted with a tracking cap (Aardex) to monitor adherence to prescribed dose and time of dosing. Participants will attend 5 clinic visits throughout the study: (1) Visit 1 (week 0) - Participants will confirm their consent to the study, undergo baseline anthropometric, glycaemic and metabolic measurements, and participate in a 5-h meal challenge during which blood will be collected to test levels of gut hormones and glycaemic biomarkers. During this visit, participants will be provided with sufficient sensors for 2 weeks, have their pump set up, and those who are using the Medtronic 670G pump will be offered an additional continuous glucose monitor (CGM, Dexcom G6) to allow research staff to monitor the participants glucose levels in real-time. At the end of the meal challenge, participants will be educated on the appropriate timing of the oral insulin dosing (1 tablet of 150IU Capsulin taken once daily, half an hour before a main meal, for one week) and have a review of home hypoglycaemia management before leaving the clinic. To note that during the first three weeks from commencement of the oral insulin, participants will be followed in real-time using the follow-function of the closed loop system or Dexcom G6. Low alerts will be enabled on the phone which will permit immediate correction of hypoglycaemia. Adjustments will be made to the pump settings if required. (2) Visit 2 (week 1) – Participants will have a clinical review of their total insulin dose, insulin sensitivity factors, insulin-carbohydrate ratios and CGM metrics. Assessment of Capsulin use and adverse events will be carried out through the review of the logbook and Aardex cap history. Participants will be provided with Capsulin for 5 weeks and will be instructed to commence intake of one tablet of 150IU Capsulin twice daily, half an hour before a main meal. (3) Visit 3 (week 6) - Participants will have a clinical review of their total insulin dose, insulin sensitivity factors, insulin-carbohydrate ratios and CGM metrics. Assessment of Capsulin use and adverse events will be carried out through the review of the logbook and Aardex cap history. CGM data and pump settings will be downloaded. Participants will be provided with Capsulin for the remaining 6 weeks and will be advised to continue intake of 150IU Capsulin twice daily, half an hour before a main meal. By Week 3, participants will have weekly contact with the research staff for the monitoring and review of their CGM. (4) Visit 4 (week 12) – Participants will undergo end-of-study anthropometric, glycaemic and metabolic measurements, and participate in a 5-h meal challenge during which blood will be collected to test levels of gut hormones and glycaemic biomarkers. CGM data and pump settings will be downloaded. Participants will be asked to report on appetite and impact on dietary intake, perceived weight loss and well-being. (5) Visit 5 (week 14) – CGM data and pump settings will be downloaded to ensure that participants are back on baseline therapy. For the 5-h meal challenge in visits 1 and 4, participants will have to attend the clinic after an overnight fast and have a subcutaneous bolus administered before consuming a standard meal. The standard meal will have a balance macronutrient composition (66% carbohydrate, 18% fat and 16% protein) and will need to be consumed within 20mins. No other oral intake (except for water) will be allowed during the monitoring period. Study participation is voluntary, and participants may withdraw at any time. Participants will be asked to discontinue the study if they have had severe hypoglycaemia (seizure or coma or any episodes requiring glucagon) or severe diabetic ketoacidosis (venous pH <7.2) or have been non-compliant with the medication which in the judgement of the investigator increases risk for the participant.