Post Approval Study of the TS (Threshold Suspend) Feature With a Sensor-Augmented Pump System Supplemented With Commercial Patient Data
The evaluation of Threshold Suspend(TS) feature is conducted by two sub-studies: 1)
Multi-Center Trial; 2) Commercial Data Evaluation. Multi-center trial is initiated to observe
the Threshold Suspend (TS) feature with a sensor-augmented insulin pump (Medtronic MiniMed®
530G insulin pump) in patients 16 and older with insulin requiring diabetes over a period of
In addition, additional data from commercial use will be analyzed/summarized to support the
Multi-center trial as the enrolled population is lower (N=426) than the anticipated N=1000
Beta Cell Restoration Through Fat Mitigation
BetaFat is a 2-arm, unblinded study to compare gastric banding to treatment with metformin
over a 24-month period in moderately obese adults with pre- or mild type 2 diabetes. The
primary outcome will be change in β-cell compensation for insulin resistance, which the
investigators will compare between groups. Secondary analyses will include other potential
markers of β-cell health and potential mediators of treatment-specific effects. The main
focus will be on mediators related to obesity. Clinically, the project will serve as a test
of concept for use of gastric banding relatively early in the spectrum of obesity and β-cell
disease. Biologically, the results will provide crucial information on potential mediators
of β-cell failure and its arrest or reversal in the context of obesity. Those mediators will
guide the development of more effective treatment and monitoring for the β-cell disease that
causes type 2 diabetes.
A Randomized Phase 2, Double-blind, Placebo-controlled, Treat-to-Target, Parallel-group,
3-arm, Multicenter Study to Assess the Efficacy and Safety of Canagliflozin as Add-on
Therapy to Insulin in the Treatment of Subjects with Type 1 Diabetes Mellitus
Canagliflozin (CANA) is an oral antihyperglycemic agent (AHA) approved for the treatment of subjects with Type 2 Diabetes Mellitus (T2DM). In subjects with T2DM, CANA lowers blood glucose by an insulin-independent mechanism and has an intrinsic low risk of hypoglycemia. In subjects with T1DM the addition of CANA to intensive insulin therapy is expected to lead to less insulin requirement which is expected to lead to a reduced insulin dose requirement, weight gain, glucose variability and low the risk of hypoglycemia. The primary objective of this study is to assess the effect of CANA 100 mg and 300 mg compared with placebo on the change in HbA1c and body weight after 18 weeks of treatment. This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, interventional study of CANA in male and female subjects between the ages of 25 years to 65 years, inclusive, with a diagnosis of T1DM for at least 1 year, and inadequate glycemic control (ie, HbA1c of 7.0% to 9.0%) on basal plus bolus insulin at screening. Approximately 330 subjects will be randomly assigned in this study (20 at the USC site), with approximately 110 subjects randomized per treatment group. The primary hypothesis will be assessed using a composite primary endpoint: proportion of subjects with HbA1c reduction 0.4% and no increase in body weight. Assuming the proportion of subjects meeting the composite criteria is 20% for placebo and 40% for each CANA dose, and assuming a 2-sided family-wise Type I error rate of 0.05, it is estimated that a sample size of 100 randomized subjects per group will be required to achieve 84% power for the comparison of each CANA dose to placebo. A modestly larger sample size (110 subjects per arm) will be randomized to each treatment arm. The modified intent-to-treat (mITT) analysis set includes all randomized subjects who have received at least 1 dose of double-blind study medication. The per-protocol (PP) analysis set consists of all mITT subjects who complete the 18-week double-blind treatment phase, and have no major protocol deviations that may affect the interpretation of the primary efficacy endpoint. The completers analysis set consists of all mITT subjects who complete the 18-week double blind treatment period. The primary efficacy endpoint will be proportion of subjects with HbA1c reduction 0.4% and no increase in body weight after 18 weeks of treatment. The primary efficacy endpoint will be analyzed longitudinally using a generalized linear mixed model. The model will include the fixed, categorical effects of treatment, stratification factor (use of CSII vs MDI), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline HbA1c, baseline body weight, and baseline-by-visit interactions. An unstructured covariance will be used to model the within-patient errors. The odds ratio and 2-sided 95% confidence interval (CI) for the treatment comparison at Week 18 (CANA vs placebo) will be estimated based on this model. As a sensitivity analysis, the last-observation-carried-forward method will be applied when the Week 18 values are missing. The odds ratio will be assessed by a logistic regression model with terms for baseline HbA1c, baseline body weight, treatment and stratification factor.
A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Type 1 Diabetes
CGM offers the opportunity to improve glycemic control, including a reduction in
hypoglycemia. Unlike home blood glucose monitors, CGM is not intended to be used directly for
making therapy adjustments and is an adjunctive device to supplement information obtained
from a standard blood glucose monitor. However, although the labeling for CGM requires a BGM
measurement before making a therapy adjustment, many CGM users often decide on a meal bolus
based on CGM alone.
A study comparing CGM used solely as an adjunctive device, as per the FDA labeling, versus
CGM used largely in lieu of BGM measurements would provide valuable data. Since many
individuals with T1D are often using CGM alone when bolusing insulin, obtaining data on the
safety and efficacy of this approach will be important. If indeed insulin dosing decisions
are proven to be safe and effective using CGM alone (without BGM confirmation) compared to
CGM with BGM confirmations, this study would also pave the way for a new standard diabetes
management protocol and therapy that would not require eight BGM measurements (i.e. finger
sticks) a day and ease the burden of managing type 1 diabetes.
For this study, participants will be randomly assigned with 2:1 probability to the CGM Only
and CGM+BGM groups, respectively. Prior to randomization, the study will be preceded by a
run-in period of up to 10 weeks to collect blinded baseline CGM data, to train the
participants on CGM use, to assess compliance with CGM use, and to initiate standard CGM use.
During the standard CGM use run-in phase, visits will occur after 2, 4 and 8 weeks, with
phone calls at 1, 3, and 6 weeks. Current CGM users may be eligible to skip part of the
run-in phase. Participants successfully completing the run-in phase will be randomized.
Both groups will use CGM devices and BGM. The CGM device to be used in the study is the
Dexcom G4 Platinum Continuous Glucose Monitoring System with modified algorithm. The CGM+BGM
group will be instructed to measure the blood glucose whenever a diabetes management decision
is made. The CGM Only group will be instructed to only measure the blood glucose (other than
for calibration) with a standard BGM meter in certain circumstances and will use a blinded
BGM meter at times when a standard BGM measurement is not done. Following randomization,
there will be a phone contact during the first week (4 to 8 days following randomization) to
address any questions the participant has about the protocol. Follow up visits will occur at
3, 6, 13, 19 and 26 weeks.