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Early terminated after prespecified interim analysis due to lack of efficacy. No relevant safety signals.
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| Name | Class |
|---|---|
| Boehringer Ingelheim | INDUSTRY |
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This randomized trial is to test whether a treatment with empagliflozin is superior to placebo in patients with postprandial hypoglycemia after bariatric surgery, that is if it improves health related quality of life (mentally or physically) or reduces the risk of hypoglycemic events.
Postprandial hypoglycemia is a debilitating medical complication after bariatric surgery for which no approved pharmacological treatment exists. The prevalence of hypoglycemia in bariatric patients ranges from 0.5 % severe episodes up to 56 % and its symptoms range from asymptomatic to deleterious. This hypoglycemic condition is characterized by a rapid increase of plasma glucose after carbohydrate ingestion followed by an exaggerated hyperinsulinemic response. Hypoglycemia itself may lead to increased hunger, carbohydrate ingestion and following weight regain.
In a placebo-controlled, randomized, double-blind, crossover study, the SGLT2-inhibitor empagliflozin statistically significantly reduced the number of symptomatic hypoglycemia (2 vs. 7 symptomatic hypoglycemic episodes; p=0.013) compared to placebo after a mixed meal test in 12 patients after Roux-en-Y gastric bypass. Empagliflozin reduced the postprandial rise in glycemia and decreased subsequent insulin secretion, underlining the postulated mechanism of action.
This randomized trial is to test whether a treatment with empagliflozin is superior to placebo in patients with postprandial hypoglycemia after bariatric surgery, that is if it improves health related quality of life (mentally or physically) or reduces the risk of hypoglycemic events.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Empagliflozin | Experimental | Standard dose of empagliflozin (Jardiance®; Boehringer Ingelheim GmbH), i. e. 10 mg. Empagliflozin is an orally available inhibitor of SGLT2 and approved for the treatment of type 2 diabetes mellitus and will be given per os once daily in the morning for 28 days. |
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| Placebo | Placebo Comparator | Placebo provided by Boehringer Ingelheim Switzerland. Per os once daily in the morning for 28 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin (Jardiance®; | Drug | Each tablet contains the active substance of 10 mg empagliflozin as well as the adjuvant lactose-monohydrate and is taken orally once daily in the morning. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Quality of life (mental health; as assessed by the SF-36 mental health component score; MCS) | Change in Quality of life (mental health; as assessed by the SF-36 mental health component. Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. | at baseline, at day 29 and at day 60 (+/- 10 days) after baseline |
| Change in Quality of life (physical health; as assessed by the SF-36 mental physical component score; PCS) | Change in Quality of life (physical health; as assessed by the SF-36 mental physical component score; PCS). Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. | at baseline, at day 29 and at day 60 (+/- 10 days) after baseline |
| Hypoglycemic events defined as glucose values below 3.0 mmol/l | Hypoglycemic events defined as glucose values below 3.0 mmol/l | at 28 days after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Postprandial Symptoms of hypoglycemia defined as acute onset of typical symptoms according to Edinburgh Hypoglycemia Scale along with a decreasing blood glucose level. | Postprandial Symptoms of hypoglycemia defined as acute onset of typical symptoms according to Edinburgh Hypoglycemia Scale (7-point Likert scale (1 = not present, 7 = very intense)) along with a decreasing blood glucose level. The postprandial period is defined as 3 hours following meal intake. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marc Y Donath, Prof. Dr. med. | University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism | Basel | 4031 | Switzerland | |||
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| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C570240 | empagliflozin |
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1:1 randomized, placebo-controlled, parallel-group double-blind superiority trial
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Both subjects and investigators will be blinded.
| Placebo Control Intervention | Other | Placebo will be provided by Boehringer Ingelheim. It is identical to the interventional product apart from the active compound. |
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| at 28 days after randomization |
| Hypoglycemia unawareness (measured by modified Clarke Score) | Hypoglycemia unawareness (measured by modified Clarke Score). The Clarke method comprises eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia. It also examines the glycemic threshold for, and symptomatic responses to, hypoglycemia. A score of four or more implies impaired awareness of hypoglycemia. | at 28 days after randomization |
| Fear of hypoglycemia (measured on a scale of 0 to 10) | Fear of hypoglycemia (measured on a scale of 0 to 10) | at 28 days after randomization |
| Time below range (TBR): % of sensor glucose readings and time between 3.0 and 3.8 mmol/L) | Time below range (TBR): % of sensor glucose readings and time between 3.0 and 3.8 mmol/L) | at 28 days after randomization |
| Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L | Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L | at 28 days after randomization |
| Pattern of sensor glucose | Pattern of sensor glucose, defined as the slope of postprandial increase (calculated as the maximal rate of increase observed over 20min in the postprandial period) and decrease (calculated as the maximal rate of decrease over 20min in the postprandial period). | at 28 days after randomization |
| Glycemic variability | Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose) | at 28 days after randomization |
| Mean amplitude of sensor glucose excursions (MAGE) | Mean amplitude of sensor glucose excursions (MAGE) | at 28 days after randomization |
| Total number of adverse events | Total number of adverse events | up to 60 days after randomization |
| Number of Serious adverse events | Number of Serious adverse events | up to 60 days after randomization |
| University Hospital Berne and Center of Bariatric Surgery Berne |
| Bern |
| 3010 |
| Switzerland |
| Cantonal Hospital Olten, Endocrine Outpatient Clinic | Olten | Switzerland |