Clinical trial NCT02258373: A Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Type 1 Diabetes
Official title: A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: Diabetes Mellitus
Continuous Glucose Monitoring
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
First posted: 2014-10-07
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Time in Range of 70 to 180 mg/dl, Measured With CGM
timeFrame: Between baseline (randomization) and 6 months
Secondary outcomes:
measure: Mean Glucose
timeFrame: Between baseline (randomization) and 6 months
measure: Measures of Glycemic Variability: Coefficient of Variation
timeFrame: Between baseline (randomization) and 6 months
measure: Percentage of Time With Sensor Value <70 mg/dl, Measured With CGM
timeFrame: Between baseline (randomization) and 6 months
measure: Percentage of Time With Sensor Values <60 mg/dl, Measured With CGM
timeFrame: Between baseline (randomization) and 6 months
measure: Percentage of Time With Sensor Values <50 mg/dl, Measured With CGM
timeFrame: Between baseline (randomization) and 6 months
measure: Percentage of Days With at Least 20 Minutes of Sensor Glucose Values <60 mg/dl
timeFrame: Between baseline (randomization) and 6 months
measure: Percentage of Time With Sensor Values >180 mg/dl, Measured With CGM
timeFrame: Between baseline (randomization) and 6 months
measure: Percentage of Time With Sensor Values > 250 mg/dl, Measured With CGM
timeFrame: Between baseline (randomization) and 6 months
measure: Percentage of Time With Sensor Values > 300 mg/dl, Measured With CGM
timeFrame: Between baseline (randomization) and 6 months
measure: Percentage of Days With at Least 20 Minutes of Sensor Glucose Values >300 mg/dl
timeFrame: Between baseline (randomization) and 6 months
measure: Change in HbA1c
timeFrame: Between baseline (randomization) and 6 months
measure: Number of Participants With no Worsening of HbA1c by Greater Than 0.3% AND no Severe Hypoglycemia Event
timeFrame: Between baseline (randomization) and 6 months
measure: Number of Participants With >=1 Severe Hypoglycemia Events
timeFrame: Between baseline (randomization) and 6 months
measure: Number of Participants With >=1 Diabetic Ketoacidosis (DKA) Events
timeFrame: Between baseline (randomization) and 6 months
measure: Number of Participants With >=1 Ketotic Events Not Meeting Criteria for DKA With Blood Ketone Level >=0.6 mmol/L
timeFrame: Between baseline (randomization) and 6 months
measure: Number of Participants With >=1 Ketotic Events Not Meeting Criteria for DKA With Blood Ketone Level >=1.0 mmol/L
timeFrame: Between baseline (randomization) and 6 months
measure: Number of Participants With >=1 Serious Adverse Event Other Than SH
timeFrame: Between baseline (randomization) and 6 months
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: University of Southern California
state: California
city: San Diego
country: United States
facility: Scripps Health
state: California
city: Denver
country: United States
facility: Barbara Davis Center for Diabetes
state: Colorado
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Des Moines
country: United States
facility: Iowa Diabetes and Endocrinology Center
state: Iowa
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: International Diabetes Center-Park Nicollet
state: Minnesota
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Jaeb Center for Health Research
name: Katrina Ruedy, MSPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.