The Effect and Safety of a Novel CGM-Based Titration Algorithm for Basal Insulin in T2DM Participants. (CGM-DTx)

An Exploratory 16-Week Pilot Study of the Effect and Safety of a Novel CGM-Based Titration Algorithm for Basal Insulin, With or Without Non-Insulin Antidiabetic Drugs, in Type 2 Diabetes Mellitus Participants Treated With Basal Insulin.

The goal of this clinical trial is to compare the effect of a continuous glucose monitor (CGM) based titration algorithm to standard titration by self-monitoring blood glucose (SMBG) in participants with Type 2 Diabetes already using long acting insulin. The comparison aims to study the difference in glycemic control between the two therapies. Participants will be followed for 18 weeks and will be provided with Degludec insulin, insulin pen, and a CGM (Dexcom G6).

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Device: Continuous Glucose Monitoring (CGM)-based titration algorithm implemented in DiAs

Detailed Description

This is an 18-week study designed to investigate the effect of a continuous glucose monitor (CGM) based titration algorithm versus a standard titration by self-monitoring blood glucose (SMBG) on glycemic control in Type 2 Diabetes (T2DM) participants using insulin Degludec. After 2 weeks of blinded CGM baseline observation, participants are randomized 2:1 to CGM-based titration or standard titration by SMBG for 16 weeks. In the SMBG group, all titrated doses will be reviewed by a study physician prior to use and participants will wear a blinded CGM during the whole study. After completion of the 16-week titration, participants are followed up for 2 days. Participants will be divided related to use of sulfonylureas or glinides with a maximum cap of nine participants being treated with sulfonylureas and glinides to complete the study.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marc D Breton, Ph.D.; Phone Number: 4349826484; Email: mb6nt@virginia.edu
• Study Contact Backup: Name: Emma G Emory, RN; Phone Number: 4342433992; Email: ee9m@uvahealth.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: Carol Levy, MD, CDE; Phone Number: 212-241-0068; Email: carol.levy@mssm.edu
      • Contact: Camilla Levister, NP, CDE; Phone Number: 212-241-5177; Email: camilla.levister@mssm.edu
      • Sub-Investigator: Selassie Ogyaadu, MD, MPH
      • Sub-Investigator: Grenye O'Malley, MD
      • Sub-Investigator: Nirali Shah, MD
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
      • Contact: Emma G Emory, RN; Phone Number: 4342433992; Email: ee9m@uvahealth.org
      • Contact: Raph Nass, MD; Phone Number: 434-982-0868; Email: rmn9a@uvahealth.org
      • Sub-Investigator: Marc D Breton, Ph.D.
      • Principal Investigator: Ralf M Nass, MD
      • Sub-Investigator: Anas El Fathi, PhD
      • Sub-Investigator: Leela Krishna Chaitanya Koravi, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older at signing of informed consent
2. Diagnosis of Type 2 Diabetes minimum 180 days before the day of screening
3. Hemoglobin A1c between 7-9% and measured by local lab at screening
4. On daily basal insulin for at least 90 days before inclusion into the study

5. Stable dose of oral and injectable (other than insulin) antidiabetic medications for 90 days prior inclusion. Acceptable medications include:

   1. Metformin
   2. Sulfonylureas
   3. Meglitinides (glinides)
   4. Dipeptidyl peptidase 4 (DPP-4) inhibitors
   5. Sodium glucose co-transporter 2 (SGLT2) inhibitors
   6. Thiazolidinediones
   7. Alpha-glucosidase inhibitors
   8. Oral combination products (for the allowed individual oral anti-diabetic drugs)
   9. Oral or injectable Glucagon-like peptide-1 (GLP-1) Receptor Agonists (RAs)
   10. If on sulfonylureas or glinides, willingness to reduce dose by 50%

Exclusion Criteria

1. Hypersensitivity to Degludec
2. Use of an insulin pump
3. Use of a short-acting insulin
4. Participation or has participated in another trial within 90 days of the screening visit
5. Female who is pregnant or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method
6. Any disorder, except for conditions associated with T2D, which in the investigator's opinion might jeopardize participant's safety or compliance with the protocol.
7. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days of the screening visit
8. Known skin reactions to CGM adhesives
9. Current/prior use of CGM within 30 days of the screening visit
10. Any planned surgery or procedures where basal insulin would be decreased or held in anticipation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous Glucose Monitoring (CGM) based Titration; The CGM-based titration algorithm will run on the Diabetes Assistant and Amazon Web Services (AWS) platform (DiAs-Cloud). DiAs-Cloud enables the seamless integration of a smart phone application and AWS server architecture to enable data capture, dose computation, review by the clinical team, and communication to study participants. For dose computation the algorithm is comprised of three components; titration glucose level, personalized target, and safety hypoglycemia feature.	Device: Continuous Glucose Monitoring (CGM)-based titration algorithm implemented in DiAs; A Continuous Glucose Monitoring (CGM)-based once weekly titration algorithm of basal insulin as implemented in DiAs Cloud platform; Other Names: Degludec
No Intervention: Standard Self-Monitoring Blood Glucose (SMBG) Titration; The SMBG-based titration algorithm will run on the Diabetes Assistant and Amazon Web Services (AWS) platform (DiAs-Cloud). DiAs-Cloud enables the seamless integration of a smart phone application and AWS server architecture to enable data capture, dose computation, review by the clinical team, and communication to study participants. Participants in the standard SMBG based titration group will wear a blinded CGM during the whole study. The total daily basal insulin dose will be converted 1:1 to Degludec. Algorithm informed dose changes will be made once weekly and checked by study physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Time in Range	Change in CGM-measured time in range 3.9-10.0 mmol/L (70-180 mg/dL) from baseline to weeks 14-16, compared between control and experimental arm.	From baseline (-2 to 0 weeks) to weeks 14-16 (2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Percent change in HbA1c	From week 0 to week 16
Change in Time in Tight Range	Percent change in time in tight range 3.9-7.8 mmol/L (70-140 mg/dL)	From baseline (week -2-0) to week 14-16
Change in Time above 10.0 mmol/L (180 mg/dL)	Percent of time spent above 10.0 mmol/L (180 mg/dL).	From baseline (week -2-0) to week 14-16
Change in Time above 13.9 mmol/L (250 mg/dL)	Percent of time spent above 13.9 mmol/L (250 mg/dL)	From baseline (week -2-0) to week 14-16
Change in Continuous Glucose Monitoring Coefficient of variation (%)	The statistical measure (%) of the relative dispersion of data points in a data series around the average CGM-measured blood glucose level.	From baseline (week -2-0) to week 14-16
Change in Mean Glucose Level	The average CGM-measured blood glucose level (mmol/L).	From baseline (week -2-0) to week 14-16
Change in Time below 3.9 mmol/L (70 mg/dL)	Percent of time spent below 3.9 mmol/L (70 mg/dL).	From baseline (week -2-0) to week 14-16
Change in Time below 3.0 mmol/L (54 mg/dL)	Percent of time spent below 3.0 mmol/L (54 mg/dL).	From baseline (week -2-0) to week 14-16
Frequency of Hypoglycemic Events	The number of clinically significant hypoglycemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycemic episodes (level 3).	From week 0 to week 16
Frequency of Serious Adverse Events	The number of serious adverse events (SAEs).	From week 0 to week 16
Frequency of Treatment Emergent Adverse Events	The number of treatment emergent adverse events (TAEs).	From week 0 to week 16
Frequency of Device Deficiencies	The number of device deficiencies (DDs). A device malfunction is any failure of a device to meet its performance specifications or otherwise work as intended. Performance specifications include all claims made in the labelling for the device. The intended performance of a device refers to the intended use for which the device is labelled or marketed.	From week 0 to week 16
Percent Acceptance Rate	Investigator acceptance rate of weekly dose guidance - from CGM-based titration (Experimental arm only).	From week 0 to week 16
Frequency of Dose Changes	The investigator changes the dose from the recommended or the current dose (Experimental arm only).	From week 0 to week 16

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: Novo Nordisk A/S
• Investigators: Study Chair: Ralf M Nass, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2023
• Primary Completion (Estimated): August 15, 2024
• Study Completion (Estimated): August 15, 2024

Study Registration Dates

• First Submitted: October 26, 2023
• First Submitted That Met QC Criteria: October 26, 2023
• First Posted (Actual): November 1, 2023

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Type 2 Diabetes; Continuous Glucose Monitoring (CGM); Self-monitoring blood glucose (SMBG); Degludec Insulin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 230357

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Will follow the NIH Data Sharing Policy and Implementation Guidance on sharing research resources for research purposes to qualified individuals in the scientific community.
• IPD Sharing Time Frame: Data will be made available after the primary publications of each study.
• IPD Sharing Access Criteria: The Data Sharing Agreements will be formulated by the study team.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes