Type 1 Diabetes Mellitus
Conditions
Brief summary
The purpose of the study is to compare the glycemic control during and following aerobic exercise using either an open or closed-loop insulin delivery system.
Detailed description
This is an open-label, single-center, randomized crossover study evaluating the performance of a closed-loop insulin delivery system using a subcutaneous glucose sensor and an external insulin pump and comparing it to an open-loop delivery system during aerobic exercise. Subject participation will be for a maximum of 16 weeks including an outpatient study (up to 6 days) and two inpatient studies (one closed-loop; the other open-loop). The closed- and open-loop visit consists of approximately 67 hours over 4 days and 3 nights.
Interventions
DEVICEClosed Loop
Insulin pump controlled by closed loop unit and algorithm
Sponsors
Juvenile Diabetes Research Foundation
Medtronic Diabetes
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects between 12-30 years of age. * Subjects must weigh at least 50 kg to accommodate phlebotomy. * Previously diagnosed Type 1 Diabetes Mellitus * Diabetes duration at least 1 year. * Currently treating their diabetes with an insulin pump. * A1C of ≤ 9.0 % at time of enrollment. * Willing to have an intravenous (IV) line inserted for frequent blood sampling and infusion of glucose if needed. * Willing to wear two (2) subcutaneous glucose sensors and two (2) transmitters simultaneously during closed-loop portion of the study. * Be in good general health without other acute or chronic illnesses except treated hypothyroidism or celiac disease and asthma not requiring glucocorticoid use. * Able to tolerate a 75-minute exercise period of moderate intensity. * Speak and understand English. * Subject and parent (if minor) must be able to comprehend and sign the informed consent form and other study documents.
Exclusion criteria
* Pregnancy (urine pregnancy test) or lactation, if female. * Subject has any major concomitant disease or any physical or psychological disorder within the last five years, which might be considered life threatening, or which might confound the collection or interpretation of the study data. * Subject has a cardiac pacemaker or similar device that may be sensitive to radio frequency telemetry. * Subject using any of the following medications: * glucocorticoids * cyclosporine * L-asparaginase * niacin * protease inhibitors * anti-psychotics * GnRH agonists * beta-blockers * calcium channel blockers * immunosuppressants * over-the-counter medications that may effect glucose metabolism. * Subject has any of the following conditions * insulin allergy * severe insulin resistance * exercise-induced asthma * musculoskeletal problems that may impact ability to complete exercise protocol * substance abuse * skin ulcers or poor wound healing * bleeding disorders * chronic infections * eating disorders * give a history of or are predisposed to major stress * any other major organ system disease. * Subject has experienced two (2) or more severe hypoglycemic events -seizures/coma requiring assistance in the past six (6) months. * Subject has any other condition that in the investigator's opinion warrants exclusion from the study or precludes him/her from completing the protocol. * Subjects using dietary supplements within 14 days of study enrollment * Subject is currently enrolled in another study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Glucose (PG) Response to Exercise | Begins at start of exercise, at or after 15:00 on the in-patient visit day randomly assigned each subject for exercise; ends at start of the subsequent meal. Median period: 121 minutes (min), interquartile range (IQR): 15 min, range: 93 to 133 min. | PG at start of exercise minus the subsequent PG nadir |
| Incidence of Hypoglycemia Immediately Following Exercise | Begins at end of exercise, at or after 16:15 on the in-patient visit day randomly assigned each subject for exercise; ends at 22:00 of same day. Median period: 333 minutes (min), interquartile range (IQR): 28 min, range: 262 to 344 min. | Tally of episodes where either plasma glucose (PG) \< 60 mg/dL, or supplemental glucose was administered to prevent imminent PG \< 60 mg/dL. Maximum tally of hypoglycemic events within any 30 minute period is 1. |
| Incidence of Nocturnal Hypoglycemia Following Exercise | Begins at 22:00 on the in-patient visit day randomly assigned each subject for exercise; ends at 6:00 of the subsequent day. Period was 480 minutes (min) for all subjects, both study phases. | Tally of episodes where either plasma glucose (PG) \< 60 mg/dL, or supplemental glucose was administered to prevent imminent PG \< 60 mg/dL. Maximum tally of hypoglycemic events within any 30 minute period is 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time Plasma Glucose (PG) is Within the Euglycemic Range. | Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total. | For each subject and arm, the percentage of the PG curve such that 70 \<= PG curve \<= 180 mg/dL. Linear interpolations furnished the data between the actual sampled PG to address potential sample influence bias arising from non-uniform sampling intervals. |
| Peak Post-prandial Plasma Glucose (PG) | Union of 6 meal periods (3 per day on study days 2 & 3). A meal period runs from meal start to start of next meal, or 22:00 for 3rd meal of the day. Union of 6 periods median: 1666 minutes (min), interquartile range (IQR): 15 min, range: 1638 to 1680 min. | For each subject and study phase, the six peak PG following each of the six meals were determined. The median of these six peaks became the one peak post-prandial PG value representing each subject and study phase. |
| Percentage of Time Plasma Glucose (PG) is Below the Euglycemic Range. | Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total. | For each subject and study phase, the percentage of the PG curve \< 70 mg/dL. Linear interpolations furnished the data between the actual sampled PG to address potential sample influence bias arising from non-uniform sampling intervals. |
| Percentage of Time Plasma Glucose (PG) is Above the Euglycemic Range. | Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total. | For each subject and study phase, the percentage of the PG curve \> 180 mg/dL. Linear interpolations furnished the data between the actual sampled PG to address potential sample influence bias arising from non-uniform sampling intervals. |
| Nadir Plasma Glucose (PG) Immediately Following Exercise | Begins at start of exercise, at or after 15:00 on the in-patient visit day randomly assigned each subject for exercise; ends at start of the subsequent meal. Median period: 121 minutes (min), interquartile range (IQR): 15 min, range: 93 to 133 min. | The PG nadir observed following the start of exercise |
| Overnight Nadir Plasma Glucose (PG) | Union of the two 8-hour overnight periods beginning at 22:00 on in-patient visit days 2 & 3, ending at 6:00 on the subsequent day. The union of the two periods was 960 minutes (min) for all subjects, both study phases. | For each subject and study phase, the overnight nadir PG for each of two nights were determined. The mean of these two nadirs became the one nadir overnight PG value representing each subject and study phase. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| First Closed Loop, Then Standard of Care or Open Loop First Closed Loop, Then Standard of Care or Open Loop | 7 |
| First Standard of Care or Open Loop, Then CLosed Loop First Standard of Care or Open Loop, Then CLosed Loop | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | First Closed Loop, Then Standard of Care or Open Loop | First Standard of Care or Open Loop, Then CLosed Loop | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 4 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Continuous | 14.4 years STANDARD_DEVIATION 2.1 | 17.7 years STANDARD_DEVIATION 4.7 | 15.9 years STANDARD_DEVIATION 3.8 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 1 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Incidence of Hypoglycemia Immediately Following Exercise
Tally of episodes where either plasma glucose (PG) \< 60 mg/dL, or supplemental glucose was administered to prevent imminent PG \< 60 mg/dL. Maximum tally of hypoglycemic events within any 30 minute period is 1.
Time frame: Begins at end of exercise, at or after 16:15 on the in-patient visit day randomly assigned each subject for exercise; ends at 22:00 of same day. Median period: 333 minutes (min), interquartile range (IQR): 28 min, range: 262 to 344 min.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Incidence of Hypoglycemia Immediately Following Exercise | 0 hypoglycemic events |
| Closed Loop (CL) Phase | Incidence of Hypoglycemia Immediately Following Exercise | 0 hypoglycemic events |
Comparison: Null hypothesis: Median tally of hypoglycemic events immediately following exercise for the OL and CL study phases do not differ.p-value: 0.5Wilcoxon (Mann-Whitney)
Primary
Incidence of Nocturnal Hypoglycemia Following Exercise
Tally of episodes where either plasma glucose (PG) \< 60 mg/dL, or supplemental glucose was administered to prevent imminent PG \< 60 mg/dL. Maximum tally of hypoglycemic events within any 30 minute period is 1.
Time frame: Begins at 22:00 on the in-patient visit day randomly assigned each subject for exercise; ends at 6:00 of the subsequent day. Period was 480 minutes (min) for all subjects, both study phases.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Incidence of Nocturnal Hypoglycemia Following Exercise | 0 hypoglycemic events |
| Closed Loop (CL) Phase | Incidence of Nocturnal Hypoglycemia Following Exercise | 0 hypoglycemic events |
Comparison: Null hypothesis: Median tally of nocturnal hypoglycemic events following exercise for the OL and CL study phases do not differ.p-value: 0.25Wilcoxon (Mann-Whitney)
Primary
Plasma Glucose (PG) Response to Exercise
PG at start of exercise minus the subsequent PG nadir
Time frame: Begins at start of exercise, at or after 15:00 on the in-patient visit day randomly assigned each subject for exercise; ends at start of the subsequent meal. Median period: 121 minutes (min), interquartile range (IQR): 15 min, range: 93 to 133 min.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Plasma Glucose (PG) Response to Exercise | 75 mg/dL |
| Closed Loop (CL) Phase | Plasma Glucose (PG) Response to Exercise | 90.5 mg/dL |
Comparison: Null hypothesis: Median change in PG concentration due to exercise for the OL and CL study phases do not differ.p-value: 0.791Wilcoxon (Mann-Whitney)
Secondary
Nadir Plasma Glucose (PG) Immediately Following Exercise
The PG nadir observed following the start of exercise
Time frame: Begins at start of exercise, at or after 15:00 on the in-patient visit day randomly assigned each subject for exercise; ends at start of the subsequent meal. Median period: 121 minutes (min), interquartile range (IQR): 15 min, range: 93 to 133 min.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Nadir Plasma Glucose (PG) Immediately Following Exercise | 80.5 mg/dL |
| Closed Loop (CL) Phase | Nadir Plasma Glucose (PG) Immediately Following Exercise | 70.5 mg/dL |
Comparison: Null hypothesis: Median nadir PG immediately following exercise for the OL and CL study phases do not differ.p-value: 0.2256Wilcoxon (Mann-Whitney)
Secondary
Overnight Nadir Plasma Glucose (PG)
For each subject and study phase, the overnight nadir PG for each of two nights were determined. The mean of these two nadirs became the one nadir overnight PG value representing each subject and study phase.
Time frame: Union of the two 8-hour overnight periods beginning at 22:00 on in-patient visit days 2 & 3, ending at 6:00 on the subsequent day. The union of the two periods was 960 minutes (min) for all subjects, both study phases.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Overnight Nadir Plasma Glucose (PG) | 74.5 mg/dL |
| Closed Loop (CL) Phase | Overnight Nadir Plasma Glucose (PG) | 93.5 mg/dL |
Comparison: Null hypothesis: Median overnight nadir PG for the OL and CL arms do not differ.p-value: 0.791Wilcoxon (Mann-Whitney)
Secondary
Peak Post-prandial Plasma Glucose (PG)
For each subject and study phase, the six peak PG following each of the six meals were determined. The median of these six peaks became the one peak post-prandial PG value representing each subject and study phase.
Time frame: Union of 6 meal periods (3 per day on study days 2 & 3). A meal period runs from meal start to start of next meal, or 22:00 for 3rd meal of the day. Union of 6 periods median: 1666 minutes (min), interquartile range (IQR): 15 min, range: 1638 to 1680 min.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Peak Post-prandial Plasma Glucose (PG) | 188 mg/dL |
| Closed Loop (CL) Phase | Peak Post-prandial Plasma Glucose (PG) | 229.75 mg/dL |
Comparison: Null hypothesis: Median peak post-prandial PG for the OL and CL study phases do not differ.p-value: 0.0669Wilcoxon (Mann-Whitney)
Secondary
Percentage of Time Plasma Glucose (PG) is Above the Euglycemic Range.
For each subject and study phase, the percentage of the PG curve \> 180 mg/dL. Linear interpolations furnished the data between the actual sampled PG to address potential sample influence bias arising from non-uniform sampling intervals.
Time frame: Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Percentage of Time Plasma Glucose (PG) is Above the Euglycemic Range. | 19.7 percentage of time |
| Closed Loop (CL) Phase | Percentage of Time Plasma Glucose (PG) is Above the Euglycemic Range. | 17.3 percentage of time |
Comparison: Null hypothesis: Median percentage of time PG is above euglycemic range for the OL and CL phases do not differ.p-value: 0.6221Wilcoxon (Mann-Whitney)
Secondary
Percentage of Time Plasma Glucose (PG) is Below the Euglycemic Range.
For each subject and study phase, the percentage of the PG curve \< 70 mg/dL. Linear interpolations furnished the data between the actual sampled PG to address potential sample influence bias arising from non-uniform sampling intervals.
Time frame: Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Percentage of Time Plasma Glucose (PG) is Below the Euglycemic Range. | 6 percentage of time |
| Closed Loop (CL) Phase | Percentage of Time Plasma Glucose (PG) is Below the Euglycemic Range. | 1.1 percentage of time |
Comparison: Null hypothesis: Median percentage of time PG is below euglycemic range for the OL and CL phases do not differ.p-value: 0.021Wilcoxon (Mann-Whitney)
Secondary
Percentage of Time Plasma Glucose (PG) is Within the Euglycemic Range.
For each subject and arm, the percentage of the PG curve such that 70 \<= PG curve \<= 180 mg/dL. Linear interpolations furnished the data between the actual sampled PG to address potential sample influence bias arising from non-uniform sampling intervals.
Time frame: Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Percentage of Time Plasma Glucose (PG) is Within the Euglycemic Range. | 74.1 percentage of time |
| Closed Loop (CL) Phase | Percentage of Time Plasma Glucose (PG) is Within the Euglycemic Range. | 79.8 percentage of time |
Comparison: Null hypothesis: Median percentage of time PG is within euglycemic range for the OL and CL phases do not differ.p-value: 0.2036Wilcoxon (Mann-Whitney)
Post Hoc
Overall Incidence of Hypoglycemia
Tally of episodes where either plasma glucose (PG) \< 60 mg/dL, or supplemental glucose was administered to prevent imminent PG \< 60 mg/dL. Maximum tally of hypoglycemic events within any 30 minute period is 1.
Time frame: Begins at 6:00 of in-patient visit day 2 and ends at 6:00 of day 4; 48 hours total.
Population: All subjects were used for final analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (OL) Phase | Overall Incidence of Hypoglycemia | 3 hypoglycemic events |
| Closed Loop (CL) Phase | Overall Incidence of Hypoglycemia | 1 hypoglycemic events |
Comparison: Null hypothesis: Median tally of hypoglycemic events over 48 hour in-patient period for the OL and CL phases do not differ.p-value: 0.0176Wilcoxon (Mann-Whitney)