Type 1 Diabetes
Conditions
Brief summary
The incidence of low blood sugar and hypoglycemic seizures at diabetes camp has been reduced thanks to overnight blood glucose level testing. The timing of the overnight blood test is often arbitrary and it is unclear when the highest frequency of nocturnal hypoglycemic events at camp are occurring. It is also unclear what the most appropriate treatment for nocturnal hypoglycemia is: simple carbohydrates, or mini-glucagon. In this study, we will use Continuous Glucose Monitors (CGMs) that will send subject data securely to a remote computer located in the medical cottage at camp throughout the night. Study staff will monitor the computer and will intervene on low blood sugar as it occurs in real time. On half of the nights, campers will receive mini-glucagon for low blood sugar, and on the rest, they will receive standard carbohydrate treatment.
Detailed description
The study will include approximately 20 subjects with Type 1 Diabetes per camp session. 10 will be linked to remote monitoring with the Diabetes Assistant Computational/Communication platform (DIAs), and 10 will wear the Dexcom CGM with the same threshold alarm setting as those wearing the DiAs (70 mg/dl), but without remote monitoring. Study participants will be between the ages of 7-21 with type 1 diabetes. This would allow for a counselor in training or a young counselor with a history of recent nocturnal hypoglycemia to be included. It is these late adolescents and young adults who often have the most severe hypoglycemic events during a camp session. We will preferentially recruit campers into the study who: 1) have a history of nocturnal hypoglycemia requiring treatment within the last 2 months, 2) have hypoglycemia unawareness confirmed with the Clark screening test, 3) have an A1c of \<8% while requiring \>0.7 units/kg/day of insulin and diabetes duration of \> 1year. At the beginning of camp, a Dexcom G4 sensor will be inserted into each participating subject and after the initial calibration, they will be calibrated with blood glucose levels in the morning and before bed each day as well as when the Dexcom sensor requests a calibration. All insulin doses and treatment decisions at camp will be based on capillary blood glucose levels and they will not be based on sensor readings. Each night, 10 of the 20 campers will be randomly assigned to remote monitoring. The randomization schedule will be computer generated prior to camp. A hypoglycemia threshold will be set for 70 mg/dl. The Dexcom communicating with the DiAs will not sound a local alarm, but an alarm will be generated at the remote monitoring. Medical personnel on call at the remote monitoring station will come to the camper's cabin and confirmatory capillary blood glucose (CBG) glucose will be obtained. If the camper is \<70 hypoglycemia, treatment will be given (we will not use predictive alarms or use the rate of change to determine treatment). Treatment will be randomized to mini-glucagon or standard oral treatment if campers are \<70 mg/dl in a 1:1 ratio. All subjects less than 70 mg/dl will then be retested in 15 minutes with a CBG to confirm recovery from hypoglycemia. If a sensor should fail or be dislodged during camp, it will be replaced. If a sensor needs to be replaced more than 2 times, a subject may be dropped and a different subject enrolled. There will be a designed medical staff person who will be monitoring subjects remotely each night. A second staff person will be available to go to subjects cabins to provide treatment for hypoglycemia. If a second event should occur at the same time, a third staff person will be on call to attend the second camper.
Interventions
DRUGMini-glucagon
Mini dose glucagon given for glucose \<70 mg/dl at a dose of 1unit/year of age
DEVICERemote monitoring
Provides real-time continuous glucose monitoring
DIETARY_SUPPLEMENTCarbohydrates
16 grams of carbohydrate
Sponsors
University of Virginia
DexCom, Inc.
The Leona M. and Harry B. Helmsley Charitable Trust
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least one year * Age 7-21 years * Attendee of Camp De Los Ninos or Conrad Chinnock * Come to camp with a consent already signed after having talked to study staff about the study, or at the onset of the camp meet with study staff and sign the consent before the first night at camp. * Using multiple daily insulin injections (Lantus) or on an insulin pump (any brand)
Exclusion criteria
* Cystic fibrosis * Medications such as current use of oral steroids or other medications, which in the judgment of the investigator would be a contraindication to participation in the study. * History of adhesive allergies which would interfere with sensor wear.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Nocturnal Hypoglycemia | 8 hours | Number of minutes with glucose reading \< 50 mg/dL. Each camper had Remote Monitoring nights and Control nights. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Glucose Readings <70 mg/dl | 8 Hours | Number of minutes with glucose reading \< 70 mg/dL. Each camper had Remote Monitoring nights and Control nights. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Prolonged Episodes of Hypoglycemic Events | 8 hours at night | Prolonged hypoglycemia is defined as glucose readings of either \<70 mg/dL for greater than one hour on and off the device, \<70 mg/dL for greater than 2 hours on and off the device, \<50 mg/dL that lasted longer than 30 minutes on and off the device and readings of \<50 mg/dL for longer than an hour, again for both the control and the subjects that were remotely monitored with the device. Each camper had Remote Monitoring nights and Control nights. |
Countries
United States
Participant flow
Recruitment details
Potential subjects were recruited from clinic; if more than 20 subjects were interested in participating in a given session, we preferentially enrolled those with a history of nocturnal awareness confirmed within the previous 2 months, (hypoglycemia unawareness confirmed with the Clarke screening test), or A1c \<8% needing \>0.7 units/kg day insulin.
Participants by arm
| Arm | Count |
|---|---|
| All Participants The subjects were enrolled at three camps for diabetes; from each camp approximately 20 subjects were enrolled. There were two locations, one hosting two sessions. Each camp was approximately 5-6 days in length. Campers wore a continuous glucose sensor every day they were in the study. On alternate nights they had remote monitoring, this defined the primary treatment arms: remote monitoring or no remote monitoring. On alternating days of remote monitoring hypoglycemia was treated with either mini glucagon or carbohydrates, this was a secondary randomization. | 57 |
| Total | 57 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 13.9 years STANDARD_DEVIATION 3.8 |
| Age, Customized 12-16 years | 39 Participants |
| Age, Customized 17-21 years | 6 Participants |
| Age, Customized 7-11 years | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants |
| Race (NIH/OMB) White | 39 Participants |
| Region of Enrollment United States | 57 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 57 | 3 / 57 |
| serious Total, serious adverse events | 0 / 57 | 0 / 57 |
Outcome results
Primary
Duration of Nocturnal Hypoglycemia
Number of minutes with glucose reading \< 50 mg/dL. Each camper had Remote Monitoring nights and Control nights.
Time frame: 8 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remote Monitoring | Duration of Nocturnal Hypoglycemia | 12.5 minutes |
| Control | Duration of Nocturnal Hypoglycemia | 15 minutes |
Comparison: The study was a feasibility and preliminary safety study. As such, the sample size was not statistically derived and the protocol was not powered to provide for definitive conclusions. The study was limited to 20 participants at each camp session. A hypoglycemic event was defined as at least two consecutive CGM readings (10 mins) below the hypoglycemic threshold of \<70 mg/dL. Recovery from a hypoglycemic event required readings above threshold for \> or = 25 minutes.p-value: 0.106Wilcoxon (Mann-Whitney)
Secondary
Duration of Glucose Readings <70 mg/dl
Number of minutes with glucose reading \< 70 mg/dL. Each camper had Remote Monitoring nights and Control nights.
Time frame: 8 Hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remote Monitoring | Duration of Glucose Readings <70 mg/dl | 30 minutes |
| Control | Duration of Glucose Readings <70 mg/dl | 35 minutes |
p-value: 0.078Wilcoxon (Mann-Whitney)
Other Pre-specified
Prolonged Episodes of Hypoglycemic Events
Prolonged hypoglycemia is defined as glucose readings of either \<70 mg/dL for greater than one hour on and off the device, \<70 mg/dL for greater than 2 hours on and off the device, \<50 mg/dL that lasted longer than 30 minutes on and off the device and readings of \<50 mg/dL for longer than an hour, again for both the control and the subjects that were remotely monitored with the device. Each camper had Remote Monitoring nights and Control nights.
Time frame: 8 hours at night
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remote Monitoring | Prolonged Episodes of Hypoglycemic Events | Events <70 mg/dL >1 hour | 7 events |
| Remote Monitoring | Prolonged Episodes of Hypoglycemic Events | Events <70 mg/dL >2hr | 0 events |
| Remote Monitoring | Prolonged Episodes of Hypoglycemic Events | Events <50 mg/dL >30 mins | 0 events |
| Remote Monitoring | Prolonged Episodes of Hypoglycemic Events | Events <50 mg/dL >1hr | 0 events |
| Control | Prolonged Episodes of Hypoglycemic Events | Events <50 mg/dL >1hr | 6 events |
| Control | Prolonged Episodes of Hypoglycemic Events | Events <70 mg/dL >1 hour | 33 events |
| Control | Prolonged Episodes of Hypoglycemic Events | Events <50 mg/dL >30 mins | 9 events |
| Control | Prolonged Episodes of Hypoglycemic Events | Events <70 mg/dL >2hr | 12 events |
Comparison: This is the P value for the number of events \<70 mg/dL longer than one hourp-value: 0.003Wilcoxon (Mann-Whitney)
Comparison: This is the p value for the number of events \<70 mg/dL that were greater than 2 hoursp-value: 0.01Fisher's exact test
Comparison: This is the p value for the number of events that were \<50 mg/dL for \> 30 minutesp-value: 0.021Fisher's exact test
Comparison: This is the P value for the number of events \<50 mg/dL that were \>1 hrp-value: 0.077Fisher's exact