Trial Outcomes & Findings for Glucose Counterregulation in Long Standing Type 1 Diabetes (NCT NCT01474889)

Results Overview

Measure of hepatic glucose output during final hour of hypoglycemic clamp. Outcome Measures are not assigned to the control groups in ct.gov as they were only used as a baseline for clinical significance. Neither group wore a CGM nor were they analyzed at 6-month and 18-month time-points.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

37 participants

Primary outcome timeframe

6 months

Results posted on

2023-08-31

Participant Flow

The Intervention Group (Group 1) consists of participants with Type 1 Diabetes complicated by Hypoglycemia Unawareness. There were two Control Groups: (Group 2) T1Ds With Intact Awareness and (Group 3) Non-diabetics are used as a baseline for clinical significance. Neither of these two Control Groups wore a CGM nor were they analyzed at 6-month and 18-month time-points.

Participant milestones

Participant milestones
Measure	Hypoglycemia Unaware T1 Diabetics This Intervention Group (Group 1) consists of participants with type 1 diabetes complicated by hypoglycemia unawareness. Patients wore an RT-CGM for 18 months. We studied glucose production and symptom generation during insulin-induced hypoglycemia (metabolic testing) by subjecting this intervention group to a pair of metabolic clamps (hypoglycemic and euglycemic) at baseline, at 6 months and at 18 months to determine if hypoglycemia avoidance can reverse unawareness.	Control Group 2 - T1Ds With Intact Awareness This control group was one of two control groups used as a baseline for clinical significance. Neither of these two control groups wore a CGM nor were they analyzed at 6-month and 18-month time-points.	Control Group 3 - Non-diabetics This control group was one of two control groups used as a baseline for clinical significance. Neither of these two control groups wore a CGM nor were they analyzed at 6-month and 18-month time-points.
Overall Study STARTED	13	12	12
Overall Study COMPLETED	11	11	12
Overall Study NOT COMPLETED	2	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Hypoglycemia Unaware T1 Diabetics This Intervention Group (Group 1) consists of participants with type 1 diabetes complicated by hypoglycemia unawareness. Patients wore an RT-CGM for 18 months. We studied glucose production and symptom generation during insulin-induced hypoglycemia (metabolic testing) by subjecting this intervention group to a pair of metabolic clamps (hypoglycemic and euglycemic) at baseline, at 6 months and at 18 months to determine if hypoglycemia avoidance can reverse unawareness.	Control Group 2 - T1Ds With Intact Awareness This control group was one of two control groups used as a baseline for clinical significance. Neither of these two control groups wore a CGM nor were they analyzed at 6-month and 18-month time-points.
Overall Study Physician Decision	1	0
Overall Study Did not meet inclusion	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Glucose Counterregulation in Long Standing Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hypoglycemia Unaware T1 Diabetics n=13 Participants This main arm is the intervention group. It consists of participants with type 1 diabetes complicated by hypoglycemia unawareness. Patients wore an RT-CGM for 18 months. We studied glucose production and symptom generation during insulin-induced hypoglycemia (metabolic testing) by subjecting this intervention group to a pair of metabolic clamps (hypoglycemic and euglycemic) at baseline, at 6 months and at 18 months to determine if hypoglycemia avoidance can reverse unawareness. RT-CGM: Each device is approximately the size of a pager and transmits with a subcutaneously placed sensor consisting of a 21 - 26 gauge needle 5 - 12 mm in length. Sensors are placed using sterile precautions and changed every 3 - 7 days depending on the manufacturers' instructions. All devices are approved as adjunctive tools to blood glucose monitoring that will be continued at least 4 times daily, before each meal and at bedtime.	Control Group 2 - T1Ds With Intact Awareness n=12 Participants Control Group 2 consists of 12 type one diabetics with intact awareness. Participants in control group 2 are enrolled as a baseline for clinical significance and not assessed for outcome measures. Control group 2 did not wear a CGM. They attended 3 visits (screening, HypoGlycemic clamp and EuGlycemic clamp) and they were not analyzed at 6-month and 18-month time-points.	Control Group 3 - Non-diabetics n=12 Participants Control Group 3 consists of 12 non-diabetics. Participants in control group 3 are enrolled as a baseline for clinical significance and not assessed for outcome measures. Control group 3 did not wear a CGM. They attended 3 visits (screening, HypoGlycemic clamp and EuGlycemic clamp) and they were not analyzed at 6-month and 18-month time-points.	Total n=37 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	37 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	46.307 years STANDARD_DEVIATION 14.343 • n=5 Participants	35.416 years STANDARD_DEVIATION 12.442 • n=7 Participants	46.166 years STANDARD_DEVIATION 7.309 • n=5 Participants	42.729 years STANDARD_DEVIATION 12.593 • n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants
Region of Enrollment United States	13 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	37 participants n=4 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Type 1 Diabetes with Hypoglycemia Unawareness. Patients wear an RT-CGM for 18 months.

Measure of hepatic glucose output during final hour of hypoglycemic clamp. Outcome Measures are not assigned to the control groups in ct.gov as they were only used as a baseline for clinical significance. Neither group wore a CGM nor were they analyzed at 6-month and 18-month time-points.

Outcome measures

Outcome measures
Measure	Hypoglycemia Unaware T1 Diabetes RT-CGM n=13 Participants This arm is the intervention group. It consists of participants with type 1 diabetes complicated by hypoglycemia unawareness. Patients wore an RT-CGM for 18 months. We studied glucose production and symptom generation during insulin-induced hypoglycemia (metabolic testing) by subjecting this intervention group to a pair of metabolic clamps (hypoglycemic and euglycemic) at baseline, at 6 months and at 18 months to determine if hypoglycemia avoidance can reverse unawareness. Please note: Arms are not assigned to the two control groups (non-diabetics and T1Ds with intact awareness) in ct.gov as they are only used as a baseline for clinical significance. Neither group wore a CGM nor are they analyzed at 6-month and 18-month time-points. RT-CGM: Each device is approximately the size of a pager and transmits with a subcutaneously placed sensor consisting of a 21 - 26 gauge needle 5 - 12 mm in length. Sensors are placed using sterile precautions and changed every 3 - 7 days depending on the manufacturers' instructions. All devices are approved as adjunctive tools to blood glucose monitoring that will be continued at least 4 times daily, before each meal and at bedtime.
Endogenous Glucose Production	0.54 mg/kg/min Standard Error 0.07

SECONDARY outcome

Timeframe: 18 months

Population: Type 1 Diabetes with Hypoglycemia Unawareness. Patients wear an RT-CGM for 18 months.

Measure of hepatic glucose output during final hour of hypoglycemic clamp

Outcome measures

Outcome measures
Measure	Hypoglycemia Unaware T1 Diabetes RT-CGM n=11 Participants This arm is the intervention group. It consists of participants with type 1 diabetes complicated by hypoglycemia unawareness. Patients wore an RT-CGM for 18 months. We studied glucose production and symptom generation during insulin-induced hypoglycemia (metabolic testing) by subjecting this intervention group to a pair of metabolic clamps (hypoglycemic and euglycemic) at baseline, at 6 months and at 18 months to determine if hypoglycemia avoidance can reverse unawareness. Please note: Arms are not assigned to the two control groups (non-diabetics and T1Ds with intact awareness) in ct.gov as they are only used as a baseline for clinical significance. Neither group wore a CGM nor are they analyzed at 6-month and 18-month time-points. RT-CGM: Each device is approximately the size of a pager and transmits with a subcutaneously placed sensor consisting of a 21 - 26 gauge needle 5 - 12 mm in length. Sensors are placed using sterile precautions and changed every 3 - 7 days depending on the manufacturers' instructions. All devices are approved as adjunctive tools to blood glucose monitoring that will be continued at least 4 times daily, before each meal and at bedtime.
Endogenous Glucose Production	0.84 mg/kg/min Standard Error 0.15

SECONDARY outcome

Timeframe: 6 months

Population: Type 1 Diabetes with Hypoglycemia Unawareness. Patients wear an RT-CGM for 18 months.

Response measure during hypoglycemic clamp using an Autonomic Symptom Questionnaire. The autonomic symptom response is calculated during the final hour of the Hypoglycemic clamp as the sum of scores ranging from 0 (none) to 5 (severe) for each of the following symptoms: anxiety, palpitations, sweating, tremor, hunger, and tingling. This results in a minimum of 0 or a maximum of 30 score with the higher score a better outcome. The scale title is Autonomic Symptom Response to hypoglycemia.

Outcome measures

Outcome measures
Measure	Hypoglycemia Unaware T1 Diabetes RT-CGM n=13 Participants This arm is the intervention group. It consists of participants with type 1 diabetes complicated by hypoglycemia unawareness. Patients wore an RT-CGM for 18 months. We studied glucose production and symptom generation during insulin-induced hypoglycemia (metabolic testing) by subjecting this intervention group to a pair of metabolic clamps (hypoglycemic and euglycemic) at baseline, at 6 months and at 18 months to determine if hypoglycemia avoidance can reverse unawareness. Please note: Arms are not assigned to the two control groups (non-diabetics and T1Ds with intact awareness) in ct.gov as they are only used as a baseline for clinical significance. Neither group wore a CGM nor are they analyzed at 6-month and 18-month time-points. RT-CGM: Each device is approximately the size of a pager and transmits with a subcutaneously placed sensor consisting of a 21 - 26 gauge needle 5 - 12 mm in length. Sensors are placed using sterile precautions and changed every 3 - 7 days depending on the manufacturers' instructions. All devices are approved as adjunctive tools to blood glucose monitoring that will be continued at least 4 times daily, before each meal and at bedtime.
Autonomic Symptom Response to Hypoglycemia	5.1 score on a scale Standard Error 1.0

SECONDARY outcome

Timeframe: 18 months

Population: Type 1 Diabetes with Hypoglycemia Unawareness. Patients wear an RT-CGM for 18 months.

Response measure during hypoglycemic clamp using an Autonomic Symptom Questionnaire. The autonomic symptom response is calculated during the final hour of the Hypoglycemic clamp as the sum of scores ranging from 0 (none) to 5 (severe) for each of the following symptoms: anxiety, palpitations, sweating, tremor, hunger, and tingling. This results in a minimum of 0 or a maximum of 30 score with the higher score a better outcome. The scale title is Autonomic Symptom Response to hypoglycemia.

Outcome measures

Outcome measures
Measure	Hypoglycemia Unaware T1 Diabetes RT-CGM n=11 Participants This arm is the intervention group. It consists of participants with type 1 diabetes complicated by hypoglycemia unawareness. Patients wore an RT-CGM for 18 months. We studied glucose production and symptom generation during insulin-induced hypoglycemia (metabolic testing) by subjecting this intervention group to a pair of metabolic clamps (hypoglycemic and euglycemic) at baseline, at 6 months and at 18 months to determine if hypoglycemia avoidance can reverse unawareness. Please note: Arms are not assigned to the two control groups (non-diabetics and T1Ds with intact awareness) in ct.gov as they are only used as a baseline for clinical significance. Neither group wore a CGM nor are they analyzed at 6-month and 18-month time-points. RT-CGM: Each device is approximately the size of a pager and transmits with a subcutaneously placed sensor consisting of a 21 - 26 gauge needle 5 - 12 mm in length. Sensors are placed using sterile precautions and changed every 3 - 7 days depending on the manufacturers' instructions. All devices are approved as adjunctive tools to blood glucose monitoring that will be continued at least 4 times daily, before each meal and at bedtime.
Autonomic Symptom Response to Hypoglycemia	5.6 score on a scale Standard Error 1.2

Adverse Events

Hypoglycemia Unaware T1 Diabetics

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Control Group 2 - T1 Diabetics

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Control Group 3 - Non Diabetics

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Cornelia V. Dalton Bakes

UPenn

Phone: 215-746-2085

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place