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| Name | Class |
|---|---|
| The Novo Nordisk Foundation Center for Basic Metabolic Research | OTHER |
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The goal of this clinical trial is to evaluate the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP) and its two isoforms, GIP[1-30] and GIP[1-42], in patients with type 1 diabetes. The main question it aims to answer is:
• What dose and isoform of GIP can most potently stimulate glucagon secretion during low blood sugar in patients with type 1 diabetes?
Participants will go through 5 experimental days that are identical except for an intravenous infusion of either placebo (saline), high or low dose GIP[1-42] or high or low dose GIP[1-30]. On all days, blood sugar will be lowered to around 2.5mmol/l for around 20-30min.
After being informed about the study and the potential risks, each participant giving written informed consent will participate in five double-blinded experimental days (Day A-E) in a randomized order. Each experimental day is identical except for an intravenous infusion of either placebo (saline), high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-42] or high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-30].
Each experimental day will consist of an induction period where the participant's blood sugar is adjusted to around 5-6mmol/l with either insulin or glucose. Then the infusion of either placebo or hormone will be initiated and continued for 135 minutes.
After 30 minutes of hormone infusion, a separate infusion of insulin (1.5mU/kg/min) will be initiated and continued for 60 minutes. Based on frequent bed-side plasma glucose measurements and an adjustable 20% glucose infusion, plasma glucose will be clamped at 2.5 mmol/l until the insulin infusion is terminated. Following this is a 45 minute recovery period, during which a minimum of glucose is infused, to ensure a steady rise from 2.5mmol/l to 3.5mmol/l.
After the study day, patients will receive a meal to prevent subsequent hypoglycemia.
The effects of each infusion will be evaluated with regards to glucagonotropic potency, as well as a series of exploratory outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Infusion of GIP[1-42], GIP[1-30] or placebo | Experimental | This is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP[1-42] B) 8pmol/kg/min GIP[1-42] C) 4pmol/kg/min GIP[1-30] D) 8pmol/kg/min GIP[1-30] E) Saline (placebo) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Infusion of GIP[1-42], GIP[1-30] or placebo | Other | This is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP[1-42] B) 8pmol/kg/min GIP[1-42] C) 4pmol/kg/min GIP[1-30] D) 8pmol/kg/min GIP[1-30] E) Saline (placebo) |
| Measure | Description | Time Frame |
|---|---|---|
| Total glucagon response | Difference in baseline subtracted area under the curve (bsAUC) for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Glucagon response during insulin infusion | Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively during the insulin infusion | 30-90minutes |
| Glucagon response after blood glucose (BG) falls below 3.0 mmol/L |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Clinical Metabolic Research, Gentofte Hospital | Hellerup | Copenhagen | 2900 | Denmark |
All published data will be made available to other researchers upon reasonable request
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Randomized, double-blinded, single-arm study. Each participant goes through five experimental days in a randomized order - acting as their own controls
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The randomized order of infusions is blinded to both participant and investigator
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|
Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively in the 30 minutes following a blood glucose of below 3.0 mmol/L |
| t[BG<3.0] and the following 30 minutes |
| Glucagon response during recovery | Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively during the recovery period | 90-135minutes |
| Total insulin response | Difference in plasma levels of insulin between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Total c-peptide response | Difference in plasma levels of c-peptide between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Amount of glucose infused | Difference in infusion rates for glucose between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Difference in epinephrine | Difference in plasma levels of epinephrine between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Difference in norepinephrine | Difference in plasma levels of norepinephrine between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Difference in cortisol | Difference in plasma levels of cortisol between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Difference in growth hormone hormones | Difference in plasma levels of growth hormone between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP) | Difference in plasma levels of P1NP between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Difference in carboxy-terminal collagen crosslinks (CTX) | Difference in plasma levels of CTX between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Difference in blood pressure | Difference in blood pressure between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| Difference in heart rate | Difference in heart rate between study days with GIP[1-42], GIP[1-30] and placebo, respectively | 0-135minutes |
| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C549099 | gastric inhibitory polypeptide (1-30) |
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