Status:
COMPLETED
Glucose Counterregulation in Long Standing Type 1 Diabetes
Lead Sponsor:
University of Pennsylvania
Collaborating Sponsors:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Conditions:
Hypoglycemia Unawareness
Type 1 Diabetes
Eligibility:
All Genders
25-70 years
Phase:
NA
Brief Summary
Enrollment for this study is complete. This study is designed to determine if use of a real-time continuous glucose monitor (RT-CGM) can reverse defective Glucose counter regulation and hypoglycemia ...
Detailed Description
The present protocol is designed to determine whether strict hypoglycemia avoidance by real-time continuous glucose monitoring (RT-CGM), can restore endogenous glucose production in response to hypogl...
Eligibility Criteria
Inclusion
- Key Inclusion Criteria for intervention GROUP 1 (Long-standing T1D complicated by hypoglycemia unawareness)
- Male and female subjects aged 25 to 70 years
- Able to provide written informed consent and to comply with the protocol procedures
- Clinical history compatible with type 1 diabetes with disease onset \< 40 years of age OR onset ≥ 40 years and documented islet autoimmunity
- Insulin-dependent for \> 10 years
- Absent C-peptide (\< 0.3 ng/mL).
- Involvement in intensive diabetes management defined as self-monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the previous 12 months.)
- Hypoglycemia unawareness manifested by a Clarke score of 4 or more AND at least one of the following:
- HYPO score greater than or equal to the 90th percentile (1047); OR marked glycemic lability defined by a glycemic lability index (LI) score greater than or equal to the 90th percentile (433 mmol/l2/h·wk-1); OR
- A composite of a HYPO score greater than or equal to the 75th percentile (423) and a LI greater than or equal to the 75th percentile (329).
- At least one episode of severe hypoglycemia in the past 12 months defined as an event with symptoms or signs compatible with hypoglycemia in which the subject was unable to treat him/herself and which was associated with either a blood glucose level \< 54 mg/dl \[3.0 mmol/L\] or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration; OR documented \> 5% time spent in the hypoglycemic range (glucose \< 60 mg/dl) by 72-hour blinded CGM.
- Key Inclusion Criteria for control GROUP 2 (Long-standing T1D with intact hypoglycemia awareness)
- Male and female subjects aged 25 to 70 years.
- Able to provide written informed consent and to comply with the procedures of the study protocol.
- Clinical history compatible with type 1 diabetes with disease onset \< 40 years of age
- Insulin-dependent for \> 10 years
- Absent C-peptide (\< 0.3 ng/mL).
- Involvement in intensive diabetes management defined as the use of basal-bolus insulin analog delivery by multi-dose injection (MDI) or continuous subcutaneous insulin infusion (CSII) together with self-monitoring of blood glucose values four or more times daily, without continuous glucose monitoring (CGM), under the direction of an endocrinologist, diabetologist, or diabetes nurse practitioner with at least 3 clinical evaluations during the previous 12 months.
- Intact hypoglycemia awareness indicated by a Clarke score of 3 or less.
- No episodes of severe hypoglycemia in the past 3 years.
- Key Inclusion Criteria for control GROUP 3 (Non-diabetic controls)
- Male and female subjects aged 25 to 70 years.
- Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol.
- No history of diabetes.
- Key Exclusion Criteria for ALL 3 groups
- Body mass index (BMI) greater than 38 kg/m2.
- Insulin requirement of more than 1.0 IU/kg/day.
- HbA1c greater than 10%.
- Untreated proliferative diabetic retinopathy.
- SBP greater than 160 mmHg or DBP greater than 100 mmHg.
- Glomerular filtration rate (GFR) less than 55 ml/min/1.73 m-squared
- Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study.
- Baseline hemoglobin less than 11 g/dl in women and less than12 g/dl in men.
- Severe co-existing cardiac disease
- Persistent elevation of liver function tests greater than 1.5 upper normal limits
- Hyperlipidemia despite medical therapy
- Receiving treatment for a medical condition requiring chronic use of systemic steroids
- Presence of a seizure disorder not attributable to hypoglycemia.
- Untreated hypothyroidism, Addisons disease, or Celiac disease.
- Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment.
- Use of RT-CGM (continuous glucose monitor) within last 4 weeks.
- Non-diabetic patients do not need to meet any of the glucose criteria.
Exclusion
Key Trial Info
Start Date :
October 1 2011
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 5 2021
Estimated Enrollment :
37 Patients enrolled
Trial Details
Trial ID
NCT01474889
Start Date
October 1 2011
End Date
March 5 2021
Last Update
August 31 2023
Active Locations (3)
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1
Clinical and Translational Research Center, Hospital of University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
2
Rodebaugh Diabetes Center, University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
3
University of Pennsylvania - Institute for Diabetes, Obesity and Metabolism
Philadelphia, Pennsylvania, United States, 19104