Trial Outcomes & Findings for Effect of Closed Loop Glucose Control on Exercise-Associated Hypoglycemia (NCT NCT00831389)

NCT ID: NCT00831389

Last Updated: 2017-12-12

Results Overview

PG at start of exercise minus the subsequent PG nadir

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 13 participants
• Primary outcome timeframe: 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.
• Results posted on: 2017-12-12

Participant Flow

Participant milestones

Measure	First Standard of Care or Open Loop, Then CLosed Loop All participants were treated and observed during in-patient visits twice during the study - two (2) in-patient study phases per subject. Each such in-patient phase was conducted for four (4) days. Insulin delivery during the first in-patient study phase was determined by either Standard of Care (OL), or autonomously by a glycemic control algorithm (CL), depending upon randomization. The exercise challenge was conducted on either the second or third day of this visit, depending upon randomization. Insulin delivery during the second in-patient study phase was the delivery mechanism not used during the 1st in-patient visit. The second in-patient study phase exercise challenge was conducted on the day not chosen for exercise during the first in-patient visit. Intervention was performed only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	First Closed Loop, Then Standard of Care or Open Loop All participants were treated and observed during in-patient visits twice during the study - two (2) in-patient study phases per subject. Each such in-patient phase was conducted for four (4) days. Insulin delivery during the first in-patient study phase was determined by either Standard of Care (OL), or autonomously by a glycemic control algorithm (CL), depending upon randomization. The exercise challenge was conducted on either the second or third day of this visit, depending upon randomization. Insulin delivery during the second in-patient study phase was the delivery mechanism not used during the 1st in-patient visit. The second in-patient study phase exercise challenge was conducted on the day not chosen for exercise during the first in-patient visit. Intervention was performed only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Overall Study STARTED	6	7
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	First Standard of Care or Open Loop, Then CLosed Loop All participants were treated and observed during in-patient visits twice during the study - two (2) in-patient study phases per subject. Each such in-patient phase was conducted for four (4) days. Insulin delivery during the first in-patient study phase was determined by either Standard of Care (OL), or autonomously by a glycemic control algorithm (CL), depending upon randomization. The exercise challenge was conducted on either the second or third day of this visit, depending upon randomization. Insulin delivery during the second in-patient study phase was the delivery mechanism not used during the 1st in-patient visit. The second in-patient study phase exercise challenge was conducted on the day not chosen for exercise during the first in-patient visit. Intervention was performed only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	First Closed Loop, Then Standard of Care or Open Loop All participants were treated and observed during in-patient visits twice during the study - two (2) in-patient study phases per subject. Each such in-patient phase was conducted for four (4) days. Insulin delivery during the first in-patient study phase was determined by either Standard of Care (OL), or autonomously by a glycemic control algorithm (CL), depending upon randomization. The exercise challenge was conducted on either the second or third day of this visit, depending upon randomization. Insulin delivery during the second in-patient study phase was the delivery mechanism not used during the 1st in-patient visit. The second in-patient study phase exercise challenge was conducted on the day not chosen for exercise during the first in-patient visit. Intervention was performed only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Effect of Closed Loop Glucose Control on Exercise-Associated Hypoglycemia

Baseline characteristics by cohort

Measure	First Closed Loop, Then Standard of Care or Open Loop n=7 Participants First Closed Loop, Then Standard of Care or Open Loop	First Standard of Care or Open Loop, Then CLosed Loop n=6 Participants First Standard of Care or Open Loop, Then CLosed Loop	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	14.4 years STANDARD_DEVIATION 2.1 • n=5 Participants	17.7 years STANDARD_DEVIATION 4.7 • n=7 Participants	15.9 years STANDARD_DEVIATION 3.8 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

PG at start of exercise minus the subsequent PG nadir

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Plasma Glucose (PG) Response to Exercise	75 mg/dL Interval 48.0 to 100.0	90.5 mg/dL Interval 59.75 to 105.0

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Incidence of Hypoglycemia Immediately Following Exercise	0 hypoglycemic events Interval 0.0 to 0.0	0 hypoglycemic events Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Incidence of Nocturnal Hypoglycemia Following Exercise	0 hypoglycemic events Interval 0.0 to 1.0	0 hypoglycemic events Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Peak Post-prandial Plasma Glucose (PG)	188 mg/dL Interval 162.5 to 227.875	229.75 mg/dL Interval 207.875 to 242.375

SECONDARY outcome

Timeframe: 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

The PG nadir observed following the start of exercise

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Nadir Plasma Glucose (PG) Immediately Following Exercise	80.5 mg/dL Interval 65.75 to 120.75	70.5 mg/dL Interval 66.75 to 80.5

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Overnight Nadir Plasma Glucose (PG)	74.5 mg/dL Interval 61.375 to 109.625	93.5 mg/dL Interval 84.5 to 97.25

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Percentage of Time Plasma Glucose (PG) is Within the Euglycemic Range.	74.1 percentage of time Interval 66.2 to 81.4	79.8 percentage of time Interval 73.3 to 83.8

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Percentage of Time Plasma Glucose (PG) is Above the Euglycemic Range.	19.7 percentage of time Interval 6.7 to 32.6	17.3 percentage of time Interval 15.6 to 21.8

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Percentage of Time Plasma Glucose (PG) is Below the Euglycemic Range.	6 percentage of time Interval 0.1 to 10.0	1.1 percentage of time Interval 0.5 to 2.9

POST_HOC outcome

Timeframe: 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

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.

Outcome measures

Measure	Standard of Care (OL) Phase n=12 Participants Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=12 Participants Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Overall Incidence of Hypoglycemia	3 hypoglycemic events Interval 0.0 to 5.5	1 hypoglycemic events Interval 0.75 to 1.0

Adverse Events

Standard of Care (OL) Phase

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Closed Loop (CL) Phase

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Standard of Care (OL) Phase n=13 participants at risk Four day inpatient visit during which insulin administration was dictated by standard of care. Subject determines basal rate, meal bolusing, and any correction boluses using her/his normal regimen. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.	Closed Loop (CL) Phase n=13 participants at risk Four day inpatient visit during which insulin administration was determined autonomously by a glycemic control algorithm, with the exception of pre-meal bolus determined by study protocol. Subject performs no adjustment to insulin dosage. Health Care Provider intervention only when dictated by protocol or determined necessary by the Health Care Professionals monitoring the study.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/13	7.7% 1/13 • Number of events 2
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/13	7.7% 1/13 • Number of events 2

Additional Information

Harry Clark

Medtronic Diabetes

Phone: 818-576-5653

Email: bud.clark@medtronic.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60