A New Wizard for Insulin Sensitivity Estimation From SAP: a Randomized Controlled Trial in Adolescents With T1D

July 10, 2019 updated by: Yale University

We aim to test the efficacy of a new method for determining individual insulin sensitivity (IS) based on sensor-augmented-insulin pump (SAP) data in order to customize the insulin to carbohydrate ratio (CR) in adolescents with type 1 diabetes (T1D).

To date, the individual insulin sensitivity (IS) could only be investigated by intensive and invasive research techniques that are not feasible to perform in an outpatient setting for pediatric patients with diabetes.

Recently published studies have demonstrated the efficacy of an algorithm to calculate the patient specific insulin sensitivity to customize the CR for adult patients with T1D. The algorithm has been validated in adult patients, however not yet investigated in the pediatric population with T1D.

The aims of our study are:

  1. to customize the CR of pediatric subjects with T1D using the individualized insulin sensitivity index (ISind) to improve post-prandial blood glucose control after a standard meal.
  2. to test, under free living condition (at home), the efficacy of the customized CR in improving post-prandial glycemic control for pediatric subjects with T1D.

This approach would have at least two potential benefits for pediatric patients with T1D:

  1. To provide a non-invasive tool for individualizing their home insulin therapy;
  2. To offer a reliable instrument for adjusting the meal bolus of the current hybrid closed loop (HCL) systems to account for the inter-subject variability in insulin action.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

A new method to assess insulin sensitivity (IS) has been proposed and investigated by the PI and his group at the University of Padova. The new insulin sensitivity index, named "SISP" is calculated from data derived from insulin pump and continuous glucose monitoring (CGM) uploads. The efficiency of the SISP has been tested in-silico using the University of Virginia/Padova T1D simulator by mimicking a single-meal scenario with patient-specific optimized carbohydrate ratio (CR) (increased or decreased by 20%) and optimal CR. In all the simulations the use of the optimal CR, calculated with the proposed method, has improved the overall glycemic control. The simulator (S2013) used for this purpose has been valdated and is approved by the FDA as a substitute for preclinical trials for insulin treatments, including closed-loop algorithms. It is comprised of data from 100 in-silico patients that represent the biological variability of a generic real diabetic population. Thus, an algorithm that is tuned on the basis of in-silico analysis can be safely implemented in real-life setting.

The method to estimate SISP and to optimize the CR from SAP data, could be easily applied to the daily management of patients with T1D and in a closed-loop context since several closed-loop algorithms, currently used in clinical trials, are based on the pre-programmed open-loop insulin therapy.

Once the individualized SISP is calculated, it can be used to customize the CR using the in-silico tested algorithm to determine an individualized CR (CRIND).

Consequently, the CRIND can be tested in outpatient setting safely, and adjusted in a run-to-run framework, using a well described approach of self-learning, the latter allowing titration of the insulin therapy based on CGM data using a self-learning algorithm as previously described.

  • Phase 1: "Control period". This phase represents the control frame-time, during which patients, once enrolled, will use their SAP without any adjustment of the CR and correction factors, according to the parameters recorded at the screening visit. This phase is aimed to record the CGM data and will represent the control period of the study. It lasts 3 weeks.
  • Phase 2: "Build-up period" This phase is aimed to obtain an adequate amount of data for customizing the insulin pump parameters to the specific features of each subject according to the proposed algorithms. It consists of three standardized meals (Figure 2) and a run-in phase.

Subjects will be randomly assigned to two different pre-meal insulin CR groups in a 1:1 ratio to determine parameters that will be used to adjust the IS algorithm for pediatric patients with T1D. The post-prandial blood glucose pattern after a pre-meal bolus of CR, CR 20% increased, CR 20% decreased are validated parameters necessary to customize the algorithm for a specific patient population with T1D, therefore subjects will be challenged with two different CRs, depending on the randomization, to collect sufficient data to fine tune the algorithm.

Each subject will go through three meal studies;

Group 1. Meal 1: CR with 20% increase; Meal 2: CR home; Meal 3: CR individualized Group 2. Meal 1: CR with 20% decrease; Meal 2: CR home; Meal 3:CR individualized

  • Before the 1st meal subjects will be randomly assigned to receive a modified premeal bolus (increased or decreased of 20%, CR+/-20%) in a 1:1 ratio. This change of the home CR (CRHOME) will allow us to estimate the accuracy and error of the CRHOME and to calculate, according to the described algorithm ((21) and below), the optimized CR (CRIND). This latter will be tested in both groups as third meal at home.
  • The three meals are followed by a 7 day- run-in period necessary to collect a minimum amount of CGM data to run the algorithm calculations used in the intervention phase. During this period subjects will adopt the CRIND obtained after the standard meals.
  • Phase 3: "Intervention period". This phase is aimed to test the efficacy of the CRIND on mitigating post-prandial hyperglycemia by a home-based study, using periodical adjustment of CR and basal rate according to the "run-to-run" approach. It consists of a self-learning algorithm method to adjust insulin regimen (the basal rate and the CRIND) based on CGM post-meal blood glucose patterns and pre-meal insulin bolus.

Subjects will use the SAP tuned according to the individualized ISR2R and CRR2R obtained from the run-in period, along with an individualized insulin basal rate (BasalR2R). During the run-to-run period subjects will receive weekly revised parameters based on run-to-run algorithm according to data analysis of the past seven days. It will last 3 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Yale Pediatric Diabetes Research Program

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 12-21 year old.
  • Clinical diagnosis of T1D ≥1 year
  • Treatment with sensor augmented pump therapy (insulin pump + glucose sensor) for at least 1 month
  • HbA1c <10%
  • Be able to comprehend written and spoken English

Exclusion Criteria

  • Pregnancy, breast feeding, or plans to get pregnant for the next 12 months
  • On medications that affect insulin sensitivity; has other medical conditions known to affect insulin sensitivity;
  • Cognitive impairment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: All participants
+Pediatric patients with T1D. All comparisons will be made within group pre and post intervention.
Other: individualized insulin sensitivity index (ISind)
The new insulin sensitivity index, named "SISP" is calculated from data derived from insulin pump and glucose monitoring (CGM) uploads.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
overall time in target (70-180mg/dl)
Time Frame: 4 weeks
the percentage of time in target will be calculated "(time in target/total time of records using continuous glucose monitoring)*100.
4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
median percentage of time spent in hypoglycemia (<70mg/dl) during control period
Time Frame: 4 weeks
the percentage of time in target will be calculated "(time in target/total time of records using continuous glucose monitoring)*100.
4 weeks
median percentage of time spent in hypoglycemia (<70mg/dl) post meal 1
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
median percentage of time spent in hypoglycemia (<70mg/dl) post meal 2
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
median percentage of time spent in hypoglycemia (<70mg/dl) post meal 3
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
median percentage of time spent in hypoglycemia (<70mg/dl) during Intervention phase
Time Frame: 4 weeks
the percentage of time in target will be calculated "(time in target/total time of records using continuous glucose monitoring)*100.
4 weeks
overall time in target (70-180mg/dl) after meal 1
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
overall time in target (70-180mg/dl) after meal 2
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
overall time in target (70-180mg/dl) after meal 3
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
overall time in target (70-180mg/dl) during Intervention phase
Time Frame: 4 weeks
the percentage of time in target will be calculated "(time in target/total time of records using continuous glucose monitoring)*100.
4 weeks
median percentage of time in hyperglycemia (>180mg/dl) during Control Phase
Time Frame: 4 weeks
time in target/total time of records using continuous glucose monitoring)*100
4 weeks
median percentage of time in hyperglycemia (>180mg/dl) after meal 1
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
median percentage of time in hyperglycemia (>180mg/dl) after meal 2
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
median percentage of time in hyperglycemia (>180mg/dl)after meal 3
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
median percentage of time in hyperglycemia (>180mg/dl) during intervention phase
Time Frame: 4 weeks
time in target/total time of records using continuous glucose monitoring)*100
4 weeks
median percentage of time below 50mg/dl during control phase
Time Frame: 4 weeks
time in target/total time of records using continuous glucose monitoring)*100
4 weeks
median percentage of time below 50mg/dl after meal 1
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
median percentage of time below 50mg/dl after meal 2
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
median percentage of time below 50mg/dl after meal 3
Time Frame: 180 minutes post meal
time in target/180 mins * 100
180 minutes post meal
median percentage of time below 50mg/dl during intervention phase
Time Frame: 4 weeks
time in target/total time of records using continuous glucose monitoring)*100
4 weeks
severe hypoglycemic events during control phase
Time Frame: 4 weeks
They will be measured as number of events per person during the weeks of Control Phase
4 weeks
severe hypoglycemic events after meal 1
Time Frame: up to 24 hours
They will be measured as number of events per person after meal 1 for the entire day
up to 24 hours
severe hypoglycemic events after meal 2
Time Frame: up to 24 hours
They will be measured as number of events per person after meal 2 for the entire day
up to 24 hours
severe hypoglycemic events after meal 3
Time Frame: up to 24 hours
They will be measured as number of events per person after meal 3 for the entire day
up to 24 hours
severe hypoglycemic events during intervention phase
Time Frame: 4 weeks
They will be measured as number of events per person during the weeks of Intervention Phase.
4 weeks
active hypoglycemia correction (carbohydrate intake) during control phase
Time Frame: 4 weeks
total number of active events per person during the weeks of Control Phase
4 weeks
active hypoglycemia correction (carbohydrate intake) after meal 1
Time Frame: up to 24 hours
total number of active events per person after meal 1 all day
up to 24 hours
active hypoglycemia correction (carbohydrate intake) after meal 2
Time Frame: up to 24 hours
total number of active events per person after meal 2 all day
up to 24 hours
active hypoglycemia correction (carbohydrate intake) after meal 3
Time Frame: up to 23 hours
total number of active events per person after meal 3 all day
up to 23 hours
active hypoglycemia correction (carbohydrate intake) during intervention phase
Time Frame: 4 weeks
total number of active events per person during the weeks of Intervention Phase
4 weeks
corrective bolus after meal during control phase
Time Frame: 4 weeks
total number of active events per person during the weeks of Control Phase vs Intervention Phase
4 weeks
corrective bolus after meal 1
Time Frame: up to 24 hours
total number of active events per person after meal 1 for the entire day
up to 24 hours
corrective bolus after meal after meal 2
Time Frame: up to 24 hours
total number of active events per person after meal 2 for the entire day
up to 24 hours
corrective bolus after meal after meal 3
Time Frame: up to 24 hours
total number of active events per person after meal 3 for the entire day
up to 24 hours
corrective bolus after meal during intervention phase
Time Frame: 4 weeks
total number of active events per person during the weeks of Intervention Phase
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Eda Cengiz, MD, Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 24, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2017

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 27, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 11, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1611018615

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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