Clinical trial NCT00406133: Randomized Study of Real-Time Continuous Glucose Monitors (RT-CGM) in the Management of Type 1 Diabetes
Official title: A Randomized Clinical Trial to Assess the Efficacy of Real-Time Continuous Glucose Monitoring (RT-CGM) in the Management of Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: JDRF Artificial Pancreas Project
First posted: 2006-12-04
Enrollment: 451
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Subjects with intensively-treated type 1 diabetes and glycated hemoglobin (HbA1c) 7.0%-10.0% in 3 age groups (\>25, 15-24, 8-14) will be randomized to a continuous glucose monitoring (CGM) group or control group. The primary outcome is change in HbA1c after 26 weeks. A parallel randomized trial is being conducted for a second cohort with HbA1c \<7.0% that will follow an identical protocol to that of the first cohort with HbA1c \>=7.0%.

The \>=7.0% trial was specifically designed and statistically powered to compare separately the impact of continuous versus standard intensive glucose monitoring in the three age groups. Both trials used standardized treatment algorithms and equivalent frequent contacts with subjects in both the CGM and control group.

After completion of the 26-week trial, the CGM group continues to use CGM for another 26 weeks to evaluate whether any beneficial effect seen in the first 6 months is sustained with longer-term use and less intensive contact and the control group initiates CGM use with less intensive contact after the first month than was provided at initiation of CGM use in the CGM group in the randomized trial.

Detailed description: 1. On the day of enrollment, a glycated hemoglobin (HbA1c) level will be obtained, psychosocial questionnaires will be completed, and instructions will be given for use of the real time continuous glucose monitoring device (RT-CGM). The study personnel will supervise the subject or parent inserting the RT-CGM sensor in the clinic and will instruct the subject or parent to insert a second sensor at home as needed. To obtain a baseline assessment of glycemic control and variability, the RT-CGM used during the first week will be blinded so subjects will not be able to view the data from the sensor. The subject will be instructed to complete at least four glucose measurements a day using the study home glucose meter (HGM) and as needed to calibrate the RT-CGM.
2. The subject will return for a second visit about 10 days after the enrollment visit.

   * Subjects who have been compliant with use of the RT-CGM and HGM will be randomized to one of two treatment groups: RT-CGM Group or Control Group.

     * Compliance will be defined as use of the RT-CGM for at least 6 out of the 7 days prior to the second visit, at least 96 hours of RT-CGM glucose values obtained with at least 24 hours between the hours of 10 p.m. and 6 a.m., and use of the HGM for testing at least 3 times each day prior to the second visit.
     * Subjects who are not compliant will be given another opportunity to complete the baseline requirements at the discretion of the investigator.
   * For the RT-CGM Group, the RT-CGM, HGM, and pump data (if subject uses an insulin pump) will be reviewed and changes will be made to diabetes management as needed. Subjects/parents will be taught to use the protocol-developed instructions for changes to diabetes management to be used in real time based on RT-CGM and HGM data. Instructions for downloading the RT-CGM and HGM will be provided to subjects with a home computer.
   * For the Control Group, a HGM and test strips will be provided. The HGM and pump data (if subject uses an insulin pump) will be reviewed and changes made in diabetes management as needed. The blinded RT-CGM data will be downloaded but will not be reviewed by study personnel until the end of the first 6 months of the study. Subjects and parents will be taught to use the protocol-developed instructions for how to make changes to diabetes management based on HGM data.
3. Both groups will have follow-up visits at 1, 4, 8, 13, 19, and 26 weeks (+/- 1 week) plus one phone contact between each visit (including one phone contact between the second visit and the one week visit) to review their diabetes management.

   * Both groups will download device data on a weekly basis (if the subject has a computer). Subjects with email access will be instructed to email the downloaded data to the clinical center prior to each phone contact.
   * For both groups, at each visit, the HGM and pump (if subject uses an insulin pump) will be downloaded and for the RT-CGM Group, the RT-CGM will be downloaded.
4. In the 13th and 26th weeks, the Control Group will use a blinded RT-CGM for one week. The RT-CGM Group will continue to use the unblinded RT-CGM. The Control Group will return the blinded RT-CGM to the clinic after a week. The data will be reviewed by personnel who are not involved in the care of the subject to determine if additional blinded sensor data are needed. The blinded data will not be reviewed by study personnel for management decisions until the end of the first 6 months of the study.
5. Following the 26-week visit:

   * Subjects in the RT-CGM Group will continue to use the RT-CGM.
   * Subjects in the Control Group will be provided with a RT-CGM and sensors after the week of blinded use and will have visits after 1 week and 4 weeks, with a phone contact during the first and third weeks.
   * Both groups will have visits after 13 weeks and 26 weeks (study time 9 and 12 months).

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least one year

  * The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.
* Age \>8 years
* Glycated hemoglobin(HbA1c) 7.0%-10.0% for the primary cohort and \<7.0% for the secondary cohort

  * The DCA2000 or comparable point of care device will be used to assess eligibility.
* Insulin regimen involves either use of an insulin pump or multiple daily injections of insulin (at least 3 shots per day) and has been stable for the last two months, with no plans to switch the modality of insulin administration during the next 6 months (e.g., injection user switching to a pump, pump user switching to injections, or the addition of Lantus (Glargine) insulin)

  * Subjects using premixed fixed doses of insulin at the time of enrollment will not be eligible
* Subject (and parent/guardian for children) understands the study protocol and agrees to comply with it
* Subjects \>9 years old and primary care giver (i.e., parent or guardian if subject is a minor) comprehend written English or Spanish

  * This requirement is due to the fact that the questionnaires to be used as outcome measures do not have validated versions in other languages.
  * Spanish-speaking subjects will be enrolled only if a RT-CGM device that functions in Spanish and has a User Guide in Spanish is available.
* No expectation that subject will be moving out of the area of the clinical center during the next year, unless the move will be to an area served by another study center.
* Informed Consent Form signed by the subject (or parent/guardian if subject is a minor, with subject signing the Child Assent Form)

Exclusion Criteria:

* The presence of a significant medical disorder or use of a medication such as oral/inhaled glucocorticoids that in the judgment of the investigator will affect the wearing of the sensors or the completion of any aspect of the protocol.
* The presence of any of the following diseases:

  * Asthma if treated with systemic or inhaled corticosteroids in the last 6 months
  * Cystic fibrosis
* Adequately treated thyroid disease and celiac disease do not exclude subjects from enrollment
* Inpatient psychiatric treatment in the past 6 months (if the subject is a minor, for either the subject or the subject's primary care giver).
* Home use of RT-CGM in past 6 months

  * Use of a CGMS or GlucoWatch does not exclude subjects from enrollment
* Participation in an intervention study (including psychological studies) in past 6 weeks.
* Another member of the same household is participating in this study.
* For females, pregnant or intending to become pregnant during the next year Pregnancy is an exclusion because of uncertainty about the lag between interstitial fluid glucose and blood glucose during pregnancy, which might affect the accuracy of the sensor. Subjects who become pregnant during the study will be discontinued from the study.

Primary outcomes:
measure: Change in Glycated Hemoglobin (HbA1c) From Baseline to 26 Weeks in the Continuous Glucose Monitoring (CGM) and Control Groups (for the Cohort With Baseline HbA1c >=7.0% Cohort)
timeFrame: Baseline and 26 weeks
measure: Time With Glucose Level <=70 mg/dL (for the Cohort With Baseline HbA1c <7.0%)
timeFrame: Baseline and 26 weeks
Secondary outcomes:
measure: Severe Hypoglycemia (for the Cohort With Baseline HbA1c >=7.0% Cohort)
timeFrame: Baseline and 26 weeks
measure: Minutes Per Day Continuous Glucose Monitoring (CGM) Glucose Values 71-180 mg/dL (for the Cohort With Baseline HbA1c >=7.0% Cohort)
timeFrame: Baseline and 26 weeks
measure: Minutes Per Day Continuous Glucose Monitoring (CGM) Glucose Values >180 mg/dL (for the Cohort With Baseline HbA1c >=7.0% Cohort)
timeFrame: Baseline and 26 weeks
measure: Minutes Per Day Continuous Glucose Monitoring (CGM) Glucose Values >250 mg/dL (for the Cohort With Baseline HbA1c >=7.0% Cohort
timeFrame: Baseline and 26 weeks
measure: Minutes Per Day Continuous Glucose Monitoring (CGM) Glucose Values <=70 mg/dL (for Cohort With Baseline HbA1c >=7.0%)
timeFrame: Baseline and 26 weeks
measure: Minutes Per Day Continuous Glucose Monitoring (CGM) Glucose Values <=50 mg/dL (for Cohort With Baseline HbA1c >=7.0%)
timeFrame: Baseline and 26 weeks
measure: Glucose (mg/dl) at Baseline and 26 Weeks (for Cohort With Baseline HbA1c >=7.0%)
timeFrame: Baseline and 26 weeks
measure: Change in Glycated Hemoglobin (HbA1c) From Baseline to 26 Weeks in the Continuous Glucose Monitoring (CGM) and Control Groups (for the Cohort With Baseline HbA1c <7.0% Cohort)
timeFrame: Baseline and 26 weeks
measure: Minutes Per Day of Continuous Glucose Monitoring (CGM) Glucose Values 71-180 mg/dL (for Cohort With Baseline HbA1c <7.0%)
timeFrame: Baseline and 26 weeks
measure: Minutes Per Day Continuous Glucose Monitoring (CGM) Glucose Values >180 mg/dL (for Cohort With Baseline HbA1c <7.0%)
timeFrame: Baseline and 26 weeks
measure: Minutes Per Day Continuous Glucose Monitoring (CGM) Glucose Values >250 mg/dL (for the Cohort With Baseline HbA1c <7.0% Cohort
timeFrame: Baseline and 26 weeks
measure: Minutes Per Day Continuous Glucose Monitoring (CGM) Glucose Values <=50 mg/dL (for Cohort With Baseline HbA1c <7.0%)
timeFrame: Baseline and 26 weeks
measure: Absolute Rate of Change (mg/dl/Min) at 26 Weeks (for Cohort With Baseline HbA1c <7.0%)
timeFrame: Baseline and 26 weeks
measure: Quality of Life
timeFrame: 26 weeks
measure: Cost-effectiveness of CGM.
timeFrame: 26 weeks
measure: QALW
timeFrame: 26 weeks
measure: Total Costs: Direct and Indirect Costs
timeFrame: 26 weeks
Other outcomes:
measure: Relative Decrease in A1c Level by >=10% (for Cohort With Baseline HbA1c >=7.0%)
timeFrame: Baseline and 26 weeks
measure: Relative Increase in A1c Level by >=10% (for Cohort With Baseline HbA1c >=7.0%)
timeFrame: Baseline and 26 weeks
measure: Relative Decrease in A1c Level by >=0.5% (for Cohort With Baseline HbA1c >=7.0%)
timeFrame: Baseline and 26 weeks
measure: Relative Increase in A1c Level by >=0.5% (for Cohort With Baseline HbA1c >=7.0%)
timeFrame: Baseline and 26 weeks
measure: 26-week A1c Level <7.0% (for Cohort With Baseline HbA1c >=7.0%)
timeFrame: Baseline and 26 weeks
measure: Decrease in A1c From Baseline by >=0.3% (for Cohort With Baseline HbA1c <7.0%)
timeFrame: Baseline and 26 weeks
measure: Increase in A1c From Baseline by >=0.3% (for Cohort With Baseline HbA1c <7.0%)
timeFrame: Baseline and 26 weeks
measure: 26-week A1c Level <7.0% (for Cohort With Baseline HbA1c <7.0%)
timeFrame: Baseline and 26 weeks
Locations:
city: Beverly Hills
country: United States
facility: University of Southern California
state: California
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Iowa City
country: United States
facility: Children's Hospital of Iowa
state: Iowa
city: Boston
country: United States
facility: Joslin Diabetes Center - Adults
state: Massachusetts
city: Boston
country: United States
facility: Joslin Diabetes Center - Children
state: Massachusetts
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Jaeb Center for Health Research
name: Roy W Beck, MD, PhD
role: STUDY_DIRECTOR
affiliation: Joslin Diabetes Center Pediatric Section
name: Lori Laffel, MD
role: STUDY_CHAIR
affiliation: Yale University
name: William V. Tamborlane, MD
role: STUDY_CHAIR
References:
citation: JDRF CGM Study Group. JDRF randomized clinical trial to assess the efficacy of real-time continuous glucose monitoring in the management of type 1 diabetes: research design and methods. Diabetes Technol Ther. 2008 Aug;10(4):310-21. doi: 10.1089/dia.2007.0302.
citation: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Tamborlane WV, Beck RW, Bode BW, Buckingham B, Chase HP, Clemons R, Fiallo-Scharer R, Fox LA, Gilliam LK, Hirsch IB, Huang ES, Kollman C, Kowalski AJ, Laffel L, Lawrence JM, Lee J, Mauras N, O'Grady M, Ruedy KJ, Tansey M, Tsalikian E, Weinzimer S, Wilson DM, Wolpert H, Wysocki T, Xing D. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med. 2008 Oct 2;359(14):1464-76. doi: 10.1056/NEJMoa0805017. Epub 2008 Sep 8.
citation: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Beck RW, Hirsch IB, Laffel L, Tamborlane WV, Bode BW, Buckingham B, Chase P, Clemons R, Fiallo-Scharer R, Fox LA, Gilliam LK, Huang ES, Kollman C, Kowalski AJ, Lawrence JM, Lee J, Mauras N, O'Grady M, Ruedy KJ, Tansey M, Tsalikian E, Weinzimer SA, Wilson DM, Wolpert H, Wysocki T, Xing D. The effect of continuous glucose monitoring in well-controlled type 1 diabetes. Diabetes Care. 2009 Aug;32(8):1378-83. doi: 10.2337/dc09-0108. Epub 2009 May 8.
citation: Wilson DM, Xing D, Cheng J, Beck RW, Hirsch I, Kollman C, Laffel L, Lawrence JM, Mauras N, Ruedy KJ, Tsalikian E, Wolpert H; Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Persistence of individual variations in glycated hemoglobin: analysis of data from the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Randomized Trial. Diabetes Care. 2011 Jun;34(6):1315-7. doi: 10.2337/dc10-1661. Epub 2011 Apr 19.
citation: Xing D, Kollman C, Beck RW, Tamborlane WV, Laffel L, Buckingham BA, Wilson DM, Weinzimer S, Fiallo-Scharer R, Ruedy KJ; Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Optimal sampling intervals to assess long-term glycemic control using continuous glucose monitoring. Diabetes Technol Ther. 2011 Mar;13(3):351-8. doi: 10.1089/dia.2010.0156. Epub 2011 Feb 7.
citation: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Fiallo-Scharer R, Cheng J, Beck RW, Buckingham BA, Chase HP, Kollman C, Laffel L, Lawrence JM, Mauras N, Tamborlane WV, Wilson DM, Wolpert H. Factors predictive of severe hypoglycemia in type 1 diabetes: analysis from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized control trial dataset. Diabetes Care. 2011 Mar;34(3):586-90. doi: 10.2337/dc10-1111. Epub 2011 Jan 25.
citation: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Wilson DM, Xing D, Beck RW, Block J, Bode B, Fox LA, Hirsch I, Kollman C, Laffel L, Ruedy KJ, Steffes M, Tamborlane WV. Hemoglobin A1c and mean glucose in patients with type 1 diabetes: analysis of data from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized trial. Diabetes Care. 2011 Mar;34(3):540-4. doi: 10.2337/dc10-1054. Epub 2011 Jan 25.
citation: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Prolonged nocturnal hypoglycemia is common during 12 months of continuous glucose monitoring in children and adults with type 1 diabetes. Diabetes Care. 2010 May;33(5):1004-8. doi: 10.2337/dc09-2081. Epub 2010 Mar 3.
citation: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Effectiveness of continuous glucose monitoring in a clinical care environment: evidence from the Juvenile Diabetes Research Foundation continuous glucose monitoring (JDRF-CGM) trial. Diabetes Care. 2010 Jan;33(1):17-22. doi: 10.2337/dc09-1502. Epub 2009 Oct 16.
citation: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Beck RW, Buckingham B, Miller K, Wolpert H, Xing D, Block JM, Chase HP, Hirsch I, Kollman C, Laffel L, Lawrence JM, Milaszewski K, Ruedy KJ, Tamborlane WV. Factors predictive of use and of benefit from continuous glucose monitoring in type 1 diabetes. Diabetes Care. 2009 Nov;32(11):1947-53. doi: 10.2337/dc09-0889. Epub 2009 Aug 12.
citation: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Bode B, Beck RW, Xing D, Gilliam L, Hirsch I, Kollman C, Laffel L, Ruedy KJ, Tamborlane WV, Weinzimer S, Wolpert H. Sustained benefit of continuous glucose monitoring on A1C, glucose profiles, and hypoglycemia in adults with type 1 diabetes. Diabetes Care. 2009 Nov;32(11):2047-9. doi: 10.2337/dc09-0846. Epub 2009 Aug 12.