A Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Type 1 Diabetes (REPLACE-BG)

• ClinicalTrials.gov Identifier: NCT02258373
• Recruitment Status: Completed
• First Posted: October 7, 2014
• Results First Posted: August 9, 2018
• Last Update Posted: August 9, 2018
• Sponsor: Jaeb Center for Health Research
• Information provided by (Responsible Party): Jaeb Center for Health Research

Study Description

Brief Summary:

The primary objective of the study is to determine whether the routine use of Continuous Glucose Monitoring (CGM) without Blood Glucose Monitoring (BGM) confirmation is as safe and effective as CGM used as an adjunct to BGM.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Device: CGM+BGM; Device: CGM Only	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 226 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Type 1 Diabetes
• Study Start Date: March 2015
• Actual Primary Completion Date: October 2016
• Actual Study Completion Date: October 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: CGM Only; Participants will be instructed to check the blood glucose with the standard study BGM for calibration of the CGM and for specific circumstances that are specified in the protocol. This group will make management decisions based on the CGM glucose value without a BGM confirmation measurement as long as the participant is confident that the CGM glucose value is not erroneous. In addition, participants will be instructed to make a BGM measurement on the blinded study BGM before going to bed, whenever an insulin bolus is given and when treating or attempting to prevent hypoglycemia and a standard BGM measurement has not been made. The participant may be asked to make post-prandial blinded BGM measurements at selected times.	Device: CGM Only; Dexcom G4 Platinum Continuous Glucose Monitoring System with modified algorithm
Active Comparator: CGM+BGM; Participants will be instructed to perform BGM measurements for sensor calibration according to Dexcom specifications and measure the blood glucose whenever a diabetes management decision is made. A BGM measurement is to be made on the study BGM before going to bed, whenever an insulin bolus is given and when treating or attempting to prevent hypoglycemia. Additional BGM measurements can be made on the study BGM at any time that the participant desires.	Device: CGM+BGM; Dexcom G4 Platinum Continuous Glucose Monitoring System with modified algorithm + Abbot Precision Xtra Blood Glucose-Ketone Meter

Outcome Measures

Primary Outcome Measures :

1. Percentage of Time in Range of 70 to 180 mg/dl, Measured With CGM [ Time Frame: Between baseline (randomization) and 6 months ]

Secondary Outcome Measures :

1. Mean Glucose [ Time Frame: Between baseline (randomization) and 6 months ]
2. Measures of Glycemic Variability: Coefficient of Variation [ Time Frame: Between baseline (randomization) and 6 months ]
   Coefficient of variation = SD/mean
3. Percentage of Time With Sensor Value <70 mg/dl, Measured With CGM [ Time Frame: Between baseline (randomization) and 6 months ]
4. Percentage of Time With Sensor Values <60 mg/dl, Measured With CGM [ Time Frame: Between baseline (randomization) and 6 months ]
5. Percentage of Time With Sensor Values <50 mg/dl, Measured With CGM [ Time Frame: Between baseline (randomization) and 6 months ]
6. Percentage of Days With at Least 20 Minutes of Sensor Glucose Values <60 mg/dl [ Time Frame: Between baseline (randomization) and 6 months ]
7. Percentage of Time With Sensor Values >180 mg/dl, Measured With CGM [ Time Frame: Between baseline (randomization) and 6 months ]
8. Percentage of Time With Sensor Values > 250 mg/dl, Measured With CGM [ Time Frame: Between baseline (randomization) and 6 months ]
9. Percentage of Time With Sensor Values > 300 mg/dl, Measured With CGM [ Time Frame: Between baseline (randomization) and 6 months ]
10. Percentage of Days With at Least 20 Minutes of Sensor Glucose Values >300 mg/dl [ Time Frame: Between baseline (randomization) and 6 months ]
11. Change in HbA1c [ Time Frame: Between baseline (randomization) and 6 months ]
12. Number of Participants With no Worsening of HbA1c by Greater Than 0.3% AND no Severe Hypoglycemia Event [ Time Frame: Between baseline (randomization) and 6 months ]
13. Number of Participants With >=1 Severe Hypoglycemia Events [ Time Frame: Between baseline (randomization) and 6 months ]
14. Number of Participants With >=1 Diabetic Ketoacidosis (DKA) Events [ Time Frame: Between baseline (randomization) and 6 months ]
15. Number of Participants With >=1 Ketotic Events Not Meeting Criteria for DKA With Blood Ketone Level >=0.6 mmol/L [ Time Frame: Between baseline (randomization) and 6 months ]
16. Number of Participants With >=1 Ketotic Events Not Meeting Criteria for DKA With Blood Ketone Level >=1.0 mmol/L [ Time Frame: Between baseline (randomization) and 6 months ]
17. Number of Participants With >=1 Serious Adverse Event Other Than SH [ Time Frame: Between baseline (randomization) and 6 months ]

    A serious adverse event is any untoward occurrence that:

    • Results in death.
    • Is life-threatening; (a non-life-threatening event which, had it been more severe, might have become life-threatening, is not necessarily considered a serious adverse event).
    • Requires inpatient hospitalization or prolongation of existing hospitalization.
    • Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions (sight threatening).
    • Is a congenital anomaly or birth defect.
    • Is considered a significant medical event by the investigator based on medical judgment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

To be eligible, all participants must meet the following inclusion criteria:

1. Clinical diagnosis of type 1 diabetes (based on investigator's judgment)
2. Age >=18 years
3. T1D duration >=1
4. HbA1c <=9.0% (a local laboratory or DCA2000 or comparable point of care device will be used to assess eligibility)
5. Use of an insulin pump for insulin delivery for at least 3 months, with no plans to discontinue pump use during the next 8 months
6. Participant is able to manage his/her diabetes with respect to insulin administration and glucose monitoring, as assessed by the investigator during the screening visit
7. Participant understands the study protocol and agrees to comply with it, including willingness to use the study CGM and BGM
8. No expectation that participant will be moving out of the area of the clinical center during the time period of the study, unless the move will be to an area served by another study center

Exclusion Criteria:

Individuals who meet any of the following criteria are not eligible for the study:

1. Severe hypoglycemia in the last 12 months in which the assistance of another individual was needed or seizure/loss of consciousness in the past 3 years

2. Significant hypoglycemia unawareness based on the Clarke Hypoglycemia Unawareness Survey defined as at least one of the following being present:

   • Survey score >2
   • Survey Q1 is answered as 'I no longer have symptoms when my blood sugar is low'
   • Survey Q7 response indicates that symptoms of hypoglycemia are not felt until glucose level is <50 mg/dl
   • Survey Q8 response is never or rarely to the question 'to what extent can you tell by your symptoms that your blood sugar is low'
3. More than one DKA event in the past year
4. History of seizures other than due to hypoglycemia
5. Current use of a threshold suspend pump feature (note: participant is eligible if a pump with this feature was being used but the threshold suspend was not active)
6. Myocardial infarction or stroke in past 6 months
7. Estimated Glomerular Filtration Rate (GFR) <30 obtained within the prior 12 months as part of usual care or kidney transplant
8. Most recent thyroid function test results abnormal, obtained as part of usual care within the prior 2 years
9. The presence of a significant medical or psychiatric disorder or use of a medication that in the judgment of the investigator will affect the wearing of the sensors, the completion of any aspect of the protocol, or increase risk
10. Cognitive difficulties that, in the judgment of the investigator, could impair the individual's ability to follow the protocol or increase risk
11. Initiation of a non-insulin drug for glucose control during the past 3 months, planned initiation during the next 8 months, or discontinuation of a non-insulin drug for glucose control during the past 3 months (note: individuals using a non-insulin medication for glucose control for 3 or more months are eligible provided there is no expectation that the medication will be discontinued during the time period of study participation)
12. Use of a systemic beta blocker drug
13. Regular use of oral corticosteroids
14. Anticipated need to use acetaminophen during the time course of the study
15. Inpatient psychiatric treatment in the past 6 months

16. Currently pregnant or lactating or plan to attempt getting pregnant during the time period of the study

    • Females with child-bearing potential will be queried about the possibility of pregnancy and a urine pregnancy test will be performed if there is uncertainty as to the possibility of pregnancy. They must agree to use appropriate birth control during the time period of the study. Participants will receive education regarding birth control methods which may be considered as highly effective, which are methods that can achieve a failure rate less than 1% per year when used consistently and correctly and include:

    • Combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
    • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
    • Intrauterine device (IUD)
    • Intrauterine hormone-releasing system (IUS)
    • Bilateral tubal occlusion
    • Vasectomised partner
    • Sexual abstinence
17. Participation in an intervention study (including psychological studies) in past 6 weeks
18. Known adhesive allergy
19. From the blinded run-in phase (or from pre-study CGM use if criteria met to skip the blinded run-in phase), CGM values <60 mg/dl for more than 10.0% of the time
20. Unsuccessful completion of the run-in phases with respect to CGM or BGM use

Contacts and Locations

Locations

United States, California

University of Southern California

Beverly Hills, California, United States, 90211

Scripps Health

San Diego, California, United States, 92121

United States, Colorado

Barbara Davis Center for Diabetes

Denver, Colorado, United States, 80045

United States, Florida

University of South Florida

Tampa, Florida, United States, 33612

United States, Georgia

Atlanta Diabetes

Atlanta, Georgia, United States, 30318

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Iowa

Iowa Diabetes and Endocrinology Center

Des Moines, Iowa, United States, 50314

United States, Massachusetts

Joslin Diabetes Center

Boston, Massachusetts, United States, 02215

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109-5456

Henry Ford Health System

Detroit, Michigan, United States, 48202

United States, Minnesota

International Diabetes Center-Park Nicollet

Minneapolis, Minnesota, United States, 55416

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104-5160

United States, Washington

University of Washington

Seattle, Washington, United States, 98105

Sponsors and Collaborators

Jaeb Center for Health Research

Investigators

• Principal Investigator: Katrina Ruedy, MSPH; Jaeb Center for Health Research

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Herrero P, Reddy M, Georgiou P, Oliver NS. Identifying Continuous Glucose Monitoring Data Using Machine Learning. Diabetes Technol Ther. 2022 Jun;24(6):403-408. doi: 10.1089/dia.2021.0498. Epub 2022 May 12.

Aleppo G, Ruedy KJ, Riddlesworth TD, Kruger DF, Peters AL, Hirsch I, Bergenstal RM, Toschi E, Ahmann AJ, Shah VN, Rickels MR, Bode BW, Philis-Tsimikas A, Pop-Busui R, Rodriguez H, Eyth E, Bhargava A, Kollman C, Beck RW; REPLACE-BG Study Group. REPLACE-BG: A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Well-Controlled Type 1 Diabetes. Diabetes Care. 2017 Apr;40(4):538-545. doi: 10.2337/dc16-2482. Epub 2017 Feb 16.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT02258373
• Other Study ID Numbers: T1DX-REPLACE-BG
• First Posted: October 7, 2014
• Results First Posted: August 9, 2018
• Last Update Posted: August 9, 2018
• Last Verified: August 2018

Keywords provided by Jaeb Center for Health Research:

Diabetes Mellitus; Continuous Glucose Monitoring

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases