Assessing efficacy and safety of Automated Insulin Delivery utilizing open source technology in children and adults with Type 1 Diabetes

INTERVENTION: The intervention in this study is the DANA‐Iâ„¢ insulin pump running in Automated Insulin Delivery (AID) mode. Following the 4‐week run‐in phase, participants will be randomly allocated to one of two treatment sequences (AA or BA) on a 1:1 basis. Treatments are as follows: A. DANA‐Iâ„¢ insulin pump running in AID mode (AnyDANA‐loop) B. DANA‐Iâ„¢ insulin pump running as Sensor Augmented Pump Therapy (SAPT) After the 6‐month RCT phase all participants will be invited into a 6‐month continuation phase and those initially randomised to SAPT cross into the AID arm. A locked version of the OpenAPS algorithm will be used and installed as an app on an Android phone (participants will be provided with this if they do not possess their own Android phone). Combined with data from the Dexcom G6 Continuous Glucose Monitor (CGM) and pump, this study AID system will be known as the “AnyDANA‐loopâ€?. This system is designed to make safe, temporary adjustments to basal insulin rates in order to maximise the time in target glucose range (3.9 ‐ 10.0 mmol/L) and minimise the risk of hypoglycaemia. In the case of failure of the system (such as phone/app failure), the pump will alert the user and switch to standard pump therapy. The algorithm is a simple, but effective, rules‐based heuristic algorithm that closely matches what a patient would do to manage their diabetes. The algorithm makes micro‐adjustments to the doses of insulin delivered every five minutes using predictions from previously inputted data and variables (such as previous insulin dosing, carbohydrate intake, CGM trend, etc.). Study Devices: All devices have been previously used in humans. The CONDITION: Metabolic and Endocrine ‐ Diabetes Type 1 Diabetes; ; Type 1 Diabetes PRIMARY OUTCOME: ; The primary outcome, mean percentage of time spent in target glucose range (3.9 to 10.0 mmol/L) will be collected from days 155 – 168 (last 2 weeks of the RCT phase), and will be calculated for each participant by dividing the number of CGM measures within range by the total number of CGM measures recorded.; [The randomised clinical trial phase is 6‐months duration, with the primary outcome will be measured at the end of this phase (day 168).]; SECONDARY OUTCOME: ; A secondary (composite) objective of this study is to evaluate the effectiveness of the Human‐Technology Interaction for both participants using AID mode as well as healthcare professionals (HCPs). ; This will be assessed by: ; ‐ ongoing content/ thematic analysis of online, peer‐to‐peer learning of participants to assess topics posted (i.e., basic functioning of AID, troubleshooting AID problems, Advanced AID use, tips and tricks for using AID, impact of AID, celebration of successes and sharing of difficulties), frequency of posts, study ID initiating posts and responding to posts (in order to establish a profile superusers including their glycaemic control and demographic characteristics). ; ‐ ongoing content analysis of online, peer‐to‐peer learning of HCPs ( (Slack Technologies Ltd, 2018) will assess frequency of posts by channel over time by HCP and Investigators, frequency of specific words in posts over time and conversation length. Analysis will focus on the topics being discussed and changes in frequency of topic, and frequency with which NI’s Crocket and Lewis provide answers vs other Healthcare Professionals providing answers over the duration of the trial. ; ‐ interviews with participants to assess their processes of learning and explore usability and acceptability of the intervention ; ‐ a focus group examining processes of learning amongst HCPs will focus on their experiences of supporting trial participants to use the AID system and the training materials provided. ; ‐ interviews with a selection of HCPs may be conducted at each site as the all participants randomised to AID complete the RCT phase to assess their experiences of supporting trial participants to use the AID system and the training materials provided. ; ‐ interviews with participants who discontinue the treatment (to occur within one month of the participant discontinuing the study) to assess usability and acceptability of the intervention.[Participant interviews will occur within 6 weeks of completing the RCT phase for those randomised to the AID arm. Thematic analysis will be undertaken on interview data. ; HCP interviews to occur within one month of the site’s last subject completing the RCT phase. ; There will be ongoing content and thematic analysis of online, peer‐to‐peer learning of participants and HCPs throughout the study duration. ; HCP focus groups to occur within one month of all sites having 5 participants complete the first three months of the RCT phase ; Interviews with participants who discontinue the treatment to occur within one month of the participant discontinuing the study.] ; ; A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to experience of fear related to hypoglycemia using the Hypoglycaemia Fear Survey II, short form. Participants aged 7‐17 years inclusive and their parent/ guardian will complete child and parent versions of the Hypoglycaemia Fear Survey (HFS II) respectively. Participants 18 years and older will complete the adult version. ; ; [This questionnaire will be completed at the baseline visit, at the end of the RCT phase and again at the end of the Continuation Phase. ; ] ; ; A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to: ; Glycaemic Control by measuring HbA1c 3 monthly (in clinics) during the RCT and continuation phase and assessment of continuous glucose monitor (CGM) data, determining % CGM time 3.0 ‐ 3.9 mmol/L, % CGM time < 3.0 mmol/L, % CGM time < 2.6 mmol/L, % CGM time 10.1 ‐13.9 mmol/L, % CGM time >13.9 mmol/L. ; This is a composite secondary outcome.[Glycaemic control based upon CGM data will be calculated for each participant for each adjacent 14 day block throughout the study (for example, day 1 to day 14, day 15 to day 28, …, day 155 to day 168). This data will be summarised as medians and quantiles by treatment group and time, and presented in figures. ] ; ; A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to: ; Glycaemic outcomes differentiated as 24 hours, day (0600‐2159 hours) and night (2200‐0559 hours)[This secondary outcome based upon CGM data will be calculated for each participant for each adjacent 14 day block throughout the study (for example, day 1 to day 14, day 15 to day 28, …, day 155 to day 168). This data will be summarised as medians and quantiles by treatment group and time, and presented in figures. ] ; ; A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to: ; Mean sensor glucose and glucose variability (expressed primarily as coefficient of variation and secondly as a SD) ; [This secondary outcome based upon CGM data will be calculated for each participant for each adjacent 14 day block throughout the study (for example, day 1 to day 14, day 15 to day 28, …, day 155 to day 168). This data will be summarised as medians and quantiles by treatment group and time, and presented in figures. ] ; ; A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to: ; Platform Performance. This will be assessed by measuring the percentage of time participants randomised to the AID arm are using AID mode. This data will be available and pulled from the cloud based severs‐ Nightscout and Dexcom Clarity. Platform performance will also be gauged by documenting any software and/ or hardware technical issues which participants can flag to study staff at any time during the entire study duration. Such issues will also be asked at clinic visits (at least 6 scheduled during the study), raised in the individual interviews (to occur after the RCT phase) for those who consent to participate in these and may also become apparent from analysis of the online peer‐peer discussions. ; [Continuous throughout the RCT and Continuation Phase.] ; ; A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to: ; Severe Adverse Events (SAE) rate: Diabetic ketoacidosis, severe hypoglycaemia. [AE collection will occur continuously. Participants will have clear instructions to contact study staff for issues such as ketones or severe hypoglycaemia. Participants will specifically be asked about any potential AEs at each study visit (at least 6 visits are scheduled).] ; A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to eating behaviors using the Research Food Diary app on four non‐consecutive days (three weekdays and one weekend day).[Participants will be asked to complete the 4 day food diary during the 4 week run in period as well as in the last week of the RCT Phase.] A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to health state (physical and mental) using the EuroQol 5‐dimensional Questionnaire (EQ‐5D). The EQ‐5D‐Y will be completed by participants 8‐15 years inclusive. The EQ‐5D‐5L will be completed by participants 16 years inclusive and older. This questionnaire will not be completed by participants 7 years of age.[The EQ‐5D will be completed at the baseline visit, at the end of the RCT phase and again at the end of the Continuation Phase.] A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to participants current treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire status (DTSQs). A Parent version of the DTSQs will be completed for participants 7‐12 years inclusive, participants 13‐17 years inclusive will complete a teen version (parents can also do this) and the adult version is to be completed by participants 18 years inclusive and older. [The DTSQs will be completed at the baseline visit, at the end of the RCT phase and again at the end of the Continuation Phase.] A secondary objective of this study is to evaluate the effectiveness of the AnyDANA‐loop platform relative to SAPT therapy, with regards to sleep quality using the Pittsburgh Sleep Quality Index in participants 13 years inclusive and older.[The PSQI will be completed at the baseline visit, at the end of the RCT phase and again at the end of the Continuation Phase.] INCLUSION CRITERIA: INCLUSION CRITERIA: 1. Type 1 diabetes as per the American Diabetes Association classification for > 1 years prior to the Baseline Visit 2. Aged 7 ‐ 70 years inclusive stratified into two groups (7 ‐ 15 years inclusive and 16 ‐ 70 years years inclusive) at Baseline 3. Currently on insulin pump therapy for > 6 months prior to the Baseline Visit 4. Mean HbA1c < 10.5% (91 mmol/mol) within 6 months prior to the Baseline Visit (minimum of one test) 5. Willing and able to adhere to the study protocol 6. Have daily access to a Wi‐Fi network