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| Name | Class |
|---|---|
| Juvenile Diabetes Research Foundation | OTHER |
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The purpose of this research study will be to test and evaluate if dapagliflozin has an effect on the amount of glucagon (a hormone produced by the pancreas and stomach that stimulates liver glucose production) produced by the body and if that change will improve recovery time from hypoglycemia (low blood sugar) in participants with Type 1 Diabetes.
The purpose of this research study will be to test and evaluate if dapagliflozin has an effect on the amount of glucagon (a hormone produced by the pancreas and stomach that stimulates liver glucose production) produced by the body and if that change will improve recovery time from hypoglycemia (low blood sugar) in participants with Type 1 Diabetes. The study is a blinded, placebo-controlled, crossover design, where participants will receive dapagliflozin during one treatment period and placebo during a separate treatment period with neither the study team nor participants knowing what they are receiving at any given time. Participants will have 9 clinic visits over the course of 14-16 weeks, with 3 of those visits being overnight stays. The overnight stays are intended to control blood sugars in a normal state throughout the night and then participants will complete a hypoglycemic challenge the following morning. The body's response to the hypoglycemic challenge will provide the information needed to determine if dapagliflozin had an effect on recovery time from hypoglycemia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dapagliflozin 5mg | Experimental |
| |
| Placebo | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dapagliflozin 5mg | Drug | Dapagliflozin treatment taken daily for 4-weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glucagon Response to Hypoglycemia | Participants will undergo a baseline hypoglycemic clamp during which glucagon will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing glucagon. | 12 Weeks |
| Epinephrine Response to Hypoglycemia | Participants will undergo a baseline hypoglycemic clamp during which epinephrine will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing epinephrine. | 12 Weeks |
| Norepinephrine Response to Hypoglycemia | Participants will undergo a baseline hypoglycemic clamp during which norepinephrine will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing norepinephrine. | 12 Weeks |
| Cortisol Response to Hypoglycemia | Participants will undergo a baseline hypoglycemic clamp during which cortisol will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing cortisol. | 12 Weeks |
| Growth Hormone Response to Hypoglycemia | Participants will undergo a baseline hypoglycemic clamp during which growth hormone will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing growth hormone. | 12 Weeks |
| Hypoglycemia Awareness | Participants will undergo a baseline hypoglycemic clamp during which they will complete the Edinburgh Hypoglycemia Scale (EHS). Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing the EHS. |
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Inclusion Criteria:
Signed and dated written informed consent by the date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation
Male or female patient receiving insulin for the treatment of documented diagnosis of T1DM for at least 1 year at the time of Visit 1
Non-fasting C-peptide < 0.7 ng/mL at Visit 1
HbA1c ≤ 10.0% at Visit 1
Based on the Investigator's judgment patient must have a good understanding of his/her disease and how to manage it, and be willing and capable of performing the following study assessments (assessed at Visits 1):
Age ≥ 18 and ≤ 70 years at Visit 1
Body Mass Index (BMI) of 18.5 kg/m2 to 35.0 kg/m2 at Visit 1
eGFR ≥ 60 mL/min/1.73m²
Patients must be able and willing to perform study assessments
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Diego Altman Clinical & Translational Research Institute | La Jolla | California | 92037 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34857545 | Derived | Boeder SC, Gregory JM, Giovannetti ER, Pettus JH. SGLT2 Inhibition Increases Fasting Glucagon but Does Not Restore the Counterregulatory Hormone Response to Hypoglycemia in Participants With Type 1 Diabetes. Diabetes. 2022 Mar 1;71(3):511-519. doi: 10.2337/db21-0769. |
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| ID | Term |
|---|---|
| C529054 | dapagliflozin |
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| Placebo Oral Tablet | Drug | Placebo treatment taken daily for 4-weeks. |
|
| 12 Weeks |
| Trails Making B Performance Response to Hypoglycemia | Participants will undergo a baseline hypoglycemic clamp during which they will complete the cognitive test, Trails Making B. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing Trails Making B. | 12 Weeks |
| Digit Symbol Substitution Performance Response to Hypoglycemia | Participants will undergo a baseline hypoglycemic clamp during which they will complete the cognitive test, Digit Symbol Substitution. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing Digit Symbol Substitution. | 12 Weeks |