{"analyses":[{"ciLowerLimit":"-0.11","ciNumSides":"TWO_SIDED","ciPctValue":"95","ciUpperLimit":"0.10","estimateComment":"Mean difference (HCL - Non-HCL) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT drug group, and clinical site.","groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY","pValue":"0.89","paramType":"Mean Difference (Final Values)","paramValue":"-0.01","statisticalComment":"The model included age, days from T1D diagnosis to randomization, and drug group as fixed effects and clinical site as a random effect.","statisticalMethod":"Mixed Models Analysis"},{"ciLowerLimit":"0.01","ciNumSides":"TWO_SIDED","ciPctValue":"95","ciUpperLimit":"0.27","estimateComment":"Mean difference (Verapamil - Placebo) at 52 weeks adjusted for age, days from T1D diagnosis to randomization, RCT intensive/standard care group, and clinical site.","groupIds":["OG002","OG003"],"nonInferiorityType":"SUPERIORITY","pValue":"0.04","paramType":"Mean Difference (Final Values)","paramValue":"0.14","statisticalComment":"The model included age, days from T1D diagnosis to randomization, and Intensive group as fixed effects and clinical site as a random effect.","statisticalMethod":"Mixed Models Analysis"}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","spread":"0.22","value":"0.57"},{"groupId":"OG001","spread":"0.18","value":"0.60"},{"groupId":"OG002","spread":"0.20","value":"0.66"},{"groupId":"OG003","spread":"0.22","value":"0.60"}]}],"title":"Randomization"},{"categories":[{"measurements":[{"groupId":"OG000","spread":"0.30","value":"0.45"},{"groupId":"OG001","spread":"0.31","value":"0.50"},{"groupId":"OG002","spread":"0.31","value":"0.65"},{"groupId":"OG003","spread":"0.30","value":"0.44"}]}],"title":"52 Weeks"}],"denoms":[{"counts":[{"groupId":"OG000","value":"61"},{"groupId":"OG001","value":"51"},{"groupId":"OG002","value":"47"},{"groupId":"OG003","value":"40"}],"units":"Participants"}],"description":"The primary outcome is the C-peptide in response to a 2-hour MMTT at 52 weeks. C-peptide was measured at 0, 15, 30, 45, 60, 90, and 120 minutes following the start of the mixed meal tolerance test (MMTT). This is summarized as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over the 120 min.","dispersionType":"Standard Deviation","groups":[{"description":"Participants assigned to HCL group will initially be randomly assigned 1:1 to use either the Tandem t:slim X2 with Control-IQ technology or a Medtronic HCL system (Medtronic 670G 4.0 AHCL (prior to protocol version 5.0) or Medtronic 780G (starting with protocol version 5.0)). This group will receive intensive diabetes management with frequent contacts by study staff with the goal of near-normalization of glucose concentrations.\n\n\\[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\\] HCL: Hybrid Closed Loop therapy verapamil","id":"OG000","title":"HCL and Intensive Management"},{"description":"Participants assigned to non-HCL will receive a Dexcom G6 CGM and diabetes management will follow usual care by their personal diabetes health care provider.\n\n\\[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\\]\n\nnon-HCL: Usual diabetes care","id":"OG001","title":"Non-HCL and Standard Care"},{"description":"Verapamil will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets.\n\nWhether drug is active or placebo is blinded to both participant and site. \\[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\\]\n\nverapamil 120mg tablet: verapamil tablet","id":"OG002","title":"Verapamil"},{"description":"Placebo will be taken orally once per day by participants in Cohort A. A dosing scheme will be followed, using 120mg tablets or 60mg half tablets.\n\nWhether drug is active or placebo is blinded to both participant and site.\n\n\\[Cohort B participants will not receive study drug. Instead, they will be randomized 2:1 to HCL or non-HCL.\\]\n\nplacebo: placebo pill manufactured to mimic verapamil 120mg tablet","id":"OG003","title":"Placebo"}],"paramType":"GEOMETRIC_MEAN","populationDescription":"1 participant randomized to Non-HCL and placebo dropped prior to baseline data being collected and was not analyzed. All other participants with at least one available measurement of C-Peptide AUC were included in the analysis model.","reportingStatus":"POSTED","timeFrame":"52 weeks","title":"C-peptide Area Under the Curve (AUC)","type":"PRIMARY","unitOfMeasure":"(pmol/ml)*minutes"}