Safety Study of Repeated Doses of Glucagon on Animal Starch in the Liver
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|ClinicalTrials.gov Identifier: NCT01986231|
Recruitment Status : Completed
First Posted : November 18, 2013
Results First Posted : April 30, 2015
Last Update Posted : May 4, 2015
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes Mellitus||Drug: Glucagon||Not Applicable|
Hypoglycemia remains a barrier to optimal glucose control, which is necessary to prevent diabetes-related complications including eye, kidney, and nerve diseases. Despite treatment advances such as insulin pump therapy and continuous glucose monitoring, hypoglycemia remains a concern, even when insulin is given in a closed-loop system. A closed-loop system consists of a glucose-measuring device, from which data are collected and entered into an algorithm, which in turn controls insulin delivery. The difficulty of delivering regular or analog insulin in such a manner is related to its slow onset and prolonged effect when delivered subcutaneously. Until a more rapidly-acting insulin preparation is available, discontinuation of subcutaneous insulin during impending hypoglycemia, with any algorithm, may be insufficient to prevent hypoglycemia.
Glucagon, a hormone secreted from the alpha cells of the normal endocrine pancreas, rapidly raises circulating glucose levels within minutes via glycogenolysis, even when given subcu-taneously. Glucagon is approved for use as a parenteral injection for treatment of severe hypoglycemia. Our group has successfully completed studies in humans using a closed-loop system that delivers insulin (in a nearly continuous fashion) to prevent and treat hyperglycemia as well as glucagon (intermittently) to prevent and treat hypoglycemia.
However, it is unknown whether or not repeated doses lead to hepatic glycogen depletion, which would increase the risk of a severe hypoglycemic episode. 13C MRS (magnetic resonance spectroscopy) has been successfully used to quantify hepatic glycogen in a non-invasive fashion. We are proposing to use 13C MRS to compare glycogen stores in subjects with type 1 diabetes after a period without glucagon vs after a period of repeated glucagon dosing. The comparisons will be made when glycogen stores should be replete (after a lunch meal) and when glycogen stores should be lower (after an overnight fast). If repeated doses of glucagon do cause glycogen depletion, then we would revise our dosing strategy in the closed-loop system and/or consider alternative methods for preventing hypoglycemia.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||The Effect of Repeated Doses of Subcutaneous Glucagon on Hepatic Glycogen Stores in Persons With Type 1 Diabetes|
|Study Start Date :||January 2011|
|Actual Primary Completion Date :||December 2012|
|Actual Study Completion Date :||December 2012|
Experimental: Open-Label Glucagon
Subjects will receive 8 doses of glucagon, each dose will be 2.0 mcg per kg.
Subjects will receive 8 doses of glucagon, each dose will be 2.0 mcg per kg. Glucagon will be reconstituted immediately prior to administration and each dose will be administered subcutaneously via syringe/needle. The first glucagon dose is at hour 17, second at hour 22, third at hour 24, fourth at hour 27, fifth at hour 29, sixth at hour 31, seventh at hour 33, eighth at hour 35.
Other Name: GlucaGen
- Assess Difference in Hepatic Glycogen Measured in the Fasting State Before vs. After Repeated Glucagon Administration [ Time Frame: Baseline and 41 hours ]The mean difference in estimated hepatic glycogen will be assessed using Carbon 13 Magnetic Resonance Spectroscopy before vs. after glucagon administration in the fasting state.
- Assess Difference in Hepatic Glycogen Measured in the Fed State Before vs. After Repeated Glucagon Administration [ Time Frame: Baseline and 41 hours ]The mean difference in estimated hepatic glycogen will be assessed using Carbon 13 Magnetic Resonance Spectroscopy before vs. after glucagon administration in the fed state.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01986231
|United States, Oregon|
|Oregon Health and Science University|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||W Kenneth Ward, MD||Legacy Health System|