Type 1 Diabetes
Conditions
Keywords
Type 1 Diabetes, Closed Loop Therapy, Continuous Glucose Monitor
Brief summary
The purpose of this study is to find out if very tight blood glucose control from the onset of Type 1 Diabetes can preserve beta cell function. Study subjects will be randomly assigned to receive either standard diabetes management or intensive diabetes management, which involves several days of closed loop therapy followed by home use of a continuous glucose monitor and insulin pump.
Detailed description
The specific aim of this study is to determine if early restoration of metabolic control will improve C-peptide production compared to children receiving routine diabetes management and the secondary aim is to determine if allowing the islet cells to be less metabolically active will have an impact on the underlying autoimmune process. Following completion of the baseline procedures (Mixed Meal Tolerance Test and blood sample collection), participants are randomized to either the Standard Treatment Group or the Intensive Treatment Group which includes 4-6 days of inpatient closed loop therapy followed by outpatient use of an insulin pump and continuous glucose monitor for diabetes management. All subjects will be seen 7 times in the first year and 4 times in the second year for follow-up testing. Subjects who are still producing insulin after 2 years may be asked to return every 6 months for an additional 2 years.
Interventions
DEVICEClosed loop
Closed loop therapy for up to 4 to 6 days
DEVICEHome glucose monitoring
Standard diabetes management using a home glucose meter.
DEVICEInsulin pump
Insulin pump use for 2 years
DEVICEContinuous glucose monitor
Continuous glucose monitor use for 2 years
Sponsors
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Age 6.0 to \<46.0 years * Diagnosis of type 1 diabetes with initiation of insulin therapy within past 7 days (day 1 being the first day of insulin therapy) * If participant is female with reproductive potential, willing to avoid pregnancy and pregnancy test negative. * Willing to accept randomization to either the intensive diabetes management group or the standard care group. * Willing to complete the planned 2 years of follow-up. * Able to electronically transmit data monthly. * Investigator believes that the participant (and parent/guardian for children) understands and agrees to comply with the study protocol and is capable of undertaking all necessary testing.
Exclusion criteria
* Currently pregnant or lactating, or anticipate getting pregnant in the next one year. * Currently anemic (hematocrit level will be obtained at the screening visit). * Chronic use of systemic steroids or other noninsulin pharmaceuticals that might affect glycemic control or the presence of a disease that is likely to be treated with such medications during the first two years of the study. * Complicating medical issues that might interfere with study conduct. * Inpatient psychiatric treatment in the past 6 months (if the participant is a minor, for either the participant or the participant's primary care giver). * Currently participating in another type 1 diabetes treatment study, including an intervention trial for treatment of diabetic ketoacidosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C-peptide Average Area Under the Curve (AUC) in Response to a Mixed Meal at 1 Year Following Enrollment. | At baseline, MMTT data were collected at 0 and 90 min; at 12 months, MMTT data were collected at 0 to 240 min post meal | In the primary analysis of the 12-month Mixed-Meal Tolerance Test (MMTT) results, the geometric mean (95% C.I.) of C-peptide average AUC (=AUC/time) was 0.43 (0.34, 0.52) pmol/ml in the intensive treatment group and 0.52 (0.32, 0.75) pmol/ml in the usual care group (P=0.49). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of the Loss of the 2 Hour Peak C-peptide < 0.2 Pmol/ml on a Semi-annual MMTT | 0 to 240 min post meal at 1 year MMTT | Outcome measure in the table is the incidence of 2 hour peak C-peptide\>=0.2 pmol/ml. Since the formal clinical trial stopped at 12 months due to lack of efficiency (later follow-up were used to collect data for secondary analyses by pooling the two groups), only the outcome at 12 months are reported. |
| HbA1c | 1 year | — |
| Adverse Events (Severe Hypoglycemia) | 1 year | — |
| Peak C-peptide in Response to a Mixed Meal at 1 Year Following Enrollment | 0 to 240 min post meal at 1 year MMTT | — |
| CGM Measured Glucose Outcomes | 1 year | Include a series of glucose indices created from CGM measured glucose data, such as % time with glucose values \<=70 mg/dl, % time with glucose values within target range of 71-180 mg/dl, % time with glucose values \>180 mg/dl, and glucose variability as measured by coefficient of variation. These indices were calculated by giving equal weight to each of the 24 h of the day. At least 24 h of CGM data were required for calculating these indices. |
| Daily Insulin Dose | 1 year | — |
| BMI Percentile | 1 year | — |
| CGM Mean Glucose | 1 year | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intensive Treatment The Intensive Treatment group will participate in 4-6 days of inpatient closed loop therapy followed by use of an insulin pump and CGM in addition to standard monitoring with a home glucose meter for 2 years. | 48 |
| Standard Treatment The Standard Care group will receive standard diabetes management using a home glucose meter for blood sugar monitoring for 2 years. | 20 |
| Total | 68 |
Baseline characteristics
| Characteristic | Standard Treatment | Intensive Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 19 Participants | 46 Participants | 65 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Continuous | 14.7 years STANDARD_DEVIATION 7.6 | 12.7 years STANDARD_DEVIATION 4.7 | 13.3 years STANDARD_DEVIATION 5.7 |
| Gender Female | 7 Participants | 17 Participants | 24 Participants |
| Gender Male | 13 Participants | 31 Participants | 44 Participants |
| Race/Ethnicity, Customized Black | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized More than one race | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Unknown | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized White | 18 participants | 42 participants | 60 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 48 | 2 / 20 |
| serious Total, serious adverse events | 2 / 48 | 1 / 20 |
Outcome results
Primary
C-peptide Average Area Under the Curve (AUC) in Response to a Mixed Meal at 1 Year Following Enrollment.
In the primary analysis of the 12-month Mixed-Meal Tolerance Test (MMTT) results, the geometric mean (95% C.I.) of C-peptide average AUC (=AUC/time) was 0.43 (0.34, 0.52) pmol/ml in the intensive treatment group and 0.52 (0.32, 0.75) pmol/ml in the usual care group (P=0.49).
Time frame: At baseline, MMTT data were collected at 0 and 90 min; at 12 months, MMTT data were collected at 0 to 240 min post meal
Population: Among the 68 participants who completed 1 year visit and with positive autoantibody, 1 participant in the intensive treatment group did not complete MMTT test, thus was excluded from all C-peptide analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Intensive Treatment | C-peptide Average Area Under the Curve (AUC) in Response to a Mixed Meal at 1 Year Following Enrollment. | 0.43 pmol/ml |
| Standard Treatment | C-peptide Average Area Under the Curve (AUC) in Response to a Mixed Meal at 1 Year Following Enrollment. | 0.52 pmol/ml |
p-value: 0.49ANCOVA
Secondary
Adverse Events (Severe Hypoglycemia)
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensive Treatment | Adverse Events (Severe Hypoglycemia) | 1 participants |
| Standard Treatment | Adverse Events (Severe Hypoglycemia) | 0 participants |
Secondary
BMI Percentile
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intensive Treatment | BMI Percentile | 58 percent |
| Standard Treatment | BMI Percentile | 62 percent |
Secondary
CGM Mean Glucose
Time frame: 1 year
Population: Participants who used CGM (either blinded or unblinded CGM) for at least 24 hours at 12 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intensive Treatment | CGM Mean Glucose | 150 mg/dL |
| Standard Treatment | CGM Mean Glucose | 152 mg/dL |
Secondary
CGM Measured Glucose Outcomes
Include a series of glucose indices created from CGM measured glucose data, such as % time with glucose values \<=70 mg/dl, % time with glucose values within target range of 71-180 mg/dl, % time with glucose values \>180 mg/dl, and glucose variability as measured by coefficient of variation. These indices were calculated by giving equal weight to each of the 24 h of the day. At least 24 h of CGM data were required for calculating these indices.
Time frame: 1 year
Population: Participants who used CGM (either blinded or unblinded CGM) for at least 24 hours at 12 months.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intensive Treatment | CGM Measured Glucose Outcomes | %Glucose 71-180 mg/dL | 69 percent |
| Intensive Treatment | CGM Measured Glucose Outcomes | %Glucose <=70 mg/dL | 2.5 percent |
| Intensive Treatment | CGM Measured Glucose Outcomes | %Glucose >180 mg/dL | 27 percent |
| Intensive Treatment | CGM Measured Glucose Outcomes | %Coefficient of variation | 35 percent |
| Standard Treatment | CGM Measured Glucose Outcomes | %Coefficient of variation | 35 percent |
| Standard Treatment | CGM Measured Glucose Outcomes | %Glucose 71-180 mg/dL | 70 percent |
| Standard Treatment | CGM Measured Glucose Outcomes | %Glucose >180 mg/dL | 22 percent |
| Standard Treatment | CGM Measured Glucose Outcomes | %Glucose <=70 mg/dL | 0.7 percent |
Secondary
Daily Insulin Dose
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intensive Treatment | Daily Insulin Dose | 0.6 u/day/kg | Standard Deviation 0.2 |
| Standard Treatment | Daily Insulin Dose | 0.6 u/day/kg | Standard Deviation 0.3 |
Secondary
HbA1c
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intensive Treatment | HbA1c | 7.4 percent | Standard Deviation 1.2 |
| Standard Treatment | HbA1c | 7.3 percent | Standard Deviation 1.1 |
p-value: 0.4ANCOVA
Secondary
Incidence of the Loss of the 2 Hour Peak C-peptide < 0.2 Pmol/ml on a Semi-annual MMTT
Outcome measure in the table is the incidence of 2 hour peak C-peptide\>=0.2 pmol/ml. Since the formal clinical trial stopped at 12 months due to lack of efficiency (later follow-up were used to collect data for secondary analyses by pooling the two groups), only the outcome at 12 months are reported.
Time frame: 0 to 240 min post meal at 1 year MMTT
Population: Among the 68 participants who completed 1 year visit and with positive autoantibody, 1 participant in the intensive treatment group did not complete MMTT test, thus was excluded from all C-peptide analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensive Treatment | Incidence of the Loss of the 2 Hour Peak C-peptide < 0.2 Pmol/ml on a Semi-annual MMTT | 37 participants |
| Standard Treatment | Incidence of the Loss of the 2 Hour Peak C-peptide < 0.2 Pmol/ml on a Semi-annual MMTT | 16 participants |
Secondary
Peak C-peptide in Response to a Mixed Meal at 1 Year Following Enrollment
Time frame: 0 to 240 min post meal at 1 year MMTT
Population: Among the 68 participants who completed 1 year visit and with positive autoantibody, 1 participant in the intensive treatment group did not complete MMTT test, thus was excluded from all C-peptide analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Intensive Treatment | Peak C-peptide in Response to a Mixed Meal at 1 Year Following Enrollment | 0.53 pmol/ml |
| Standard Treatment | Peak C-peptide in Response to a Mixed Meal at 1 Year Following Enrollment | 0.65 pmol/ml |