Back to resultsEmpagliflozin for the Treatment of Postprandial Hypoglycemia (EmpHy)
Primary Purpose
Postprandial Hypoglycemia
Status
Recruiting
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
Empagliflozin (Jardiance®;
Placebo Control Intervention
Sponsored by
About this trial
This is an interventional treatment trial for Postprandial Hypoglycemia focused on measuring Empagliflozin, bariatric surgery, hyperinsulinemic response, SGLT2-inhibitor, insulin secretion, postbariatric hypoglycemia
Eligibility Criteria
Inclusion Criteria:
- Patients after bariatric surgery (i.e. sleeve gastrectomy, Roux-en-Y gastric bypass, omega- loop bypass, biliopancreatic diversion) with documented hypoglycemia, i. e. < 3.0 mmol/l and at least 5 hypoglycemic episodes per week despite dietary modification
- For women with child-bearing potential, willingness to use contraceptive measures adequate to prevent pregnancy during the study
- Informed Consent as documented by signature
Exclusion Criteria:
- Any type of diabetes mellitus according to ADA criteria
- Intolerance to the study drug
- Signs of current infection
- Use of any drug therapy for postbariatric hypoglycemia apart from acarbose (all remaining drugs have to be discontinued four half-life times before screening phase)
- Neutropenia (leukocyte count < 1.5 × 109/L or absolute neutrophil count (ANC) < 0.5 × 109/L)
- Anemia (hemoglobin < 11 g/dL for males, < 10 g/dL for females)
- Clinically significant kidney or liver disease (creatinine > 1.5 mg/dL, AST/ALT > 2 × ULN, alkaline phosphatase > 2 × ULN, or total bilirubin [tBili] > 1.5 × ULN)
- Uncontrolled congestive heart failure
- Uncontrolled malignant disease
- Currently pregnant or breastfeeding
- Known or suspected non-compliance, drug or alcohol abuse
- Meeting the criteria for vulnerability (e.g. participants incapable of judgment or participants under tutelage)
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.
- Participation in another clinical trial using investigational drugs in the last 30 days or planned participation in the next 60 days
- Previous enrolment into the current study,
- Enrolment of the investigator, his/her family members, employees and other dependent persons
Sites / Locations
- University Hospital Basel, Division of Endocrinology, Diabetes and MetabolismRecruiting
- University Hospital Berne and Center of Bariatric Surgery BerneRecruiting
- Cantonal Hospital Olten, Endocrine Outpatient ClinicRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Empagliflozin
Placebo
Arm Description
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.
Placebo provided by Boehringer Ingelheim Switzerland. Per os once daily in the morning for 28 days.
Outcomes
Primary Outcome Measures
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.
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.
Hypoglycemic events defined as glucose values below 3.0 mmol/l
Hypoglycemic events defined as glucose values below 3.0 mmol/l
Secondary Outcome Measures
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.
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.
Fear of hypoglycemia (measured on a scale of 0 to 10)
Fear of hypoglycemia (measured on a scale of 0 to 10)
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)
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
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).
Glycemic variability
Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)
Mean amplitude of sensor glucose excursions (MAGE)
Mean amplitude of sensor glucose excursions (MAGE)
Total number of adverse events
Total number of adverse events
Number of Serious adverse events
Number of Serious adverse events
Full Information
NCT ID
NCT05036317
First Posted
September 1, 2021
Last Updated
April 3, 2023
Sponsor
University Hospital, Basel, Switzerland
Collaborators
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT05036317
Brief Title
Empagliflozin for the Treatment of Postprandial Hypoglycemia
Acronym
EmpHy
Official Title
Empagliflozin for the Treatment of Postprandial Hypoglycemia
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 11, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
Collaborators
Boehringer Ingelheim
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postprandial Hypoglycemia
Keywords
Empagliflozin, bariatric surgery, hyperinsulinemic response, SGLT2-inhibitor, insulin secretion, postbariatric hypoglycemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
1:1 randomized, placebo-controlled, parallel-group double-blind superiority trial
Masking
ParticipantInvestigator
Masking Description
Both subjects and investigators will be blinded.
Allocation
Randomized
Enrollment
62 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Empagliflozin
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo provided by Boehringer Ingelheim Switzerland. Per os once daily in the morning for 28 days.
Intervention Type
Drug
Intervention Name(s)
Empagliflozin (Jardiance®;
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo Control Intervention
Intervention Description
Placebo will be provided by Boehringer Ingelheim. It is identical to the interventional product apart from the active compound.
Primary Outcome Measure Information:
Title
Change in Quality of life (mental health; as assessed by the SF-36 mental health component score; MCS)
Description
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.
Time Frame
at baseline, at day 29 and at day 60 (+/- 10 days) after baseline
Title
Change in Quality of life (physical health; as assessed by the SF-36 mental physical component score; PCS)
Description
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.
Time Frame
at baseline, at day 29 and at day 60 (+/- 10 days) after baseline
Title
Hypoglycemic events defined as glucose values below 3.0 mmol/l
Description
Hypoglycemic events defined as glucose values below 3.0 mmol/l
Time Frame
at 28 days after randomization
Secondary Outcome Measure Information:
Title
Postprandial Symptoms of hypoglycemia defined as acute onset of typical symptoms according to Edinburgh Hypoglycemia Scale along with a decreasing blood glucose level.
Description
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.
Time Frame
at 28 days after randomization
Title
Hypoglycemia unawareness (measured by modified Clarke Score)
Description
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.
Time Frame
at 28 days after randomization
Title
Fear of hypoglycemia (measured on a scale of 0 to 10)
Description
Fear of hypoglycemia (measured on a scale of 0 to 10)
Time Frame
at 28 days after randomization
Title
Time below range (TBR): % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)
Description
Time below range (TBR): % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)
Time Frame
at 28 days after randomization
Title
Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L
Description
Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L
Time Frame
at 28 days after randomization
Title
Pattern of sensor glucose
Description
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).
Time Frame
at 28 days after randomization
Title
Glycemic variability
Description
Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)
Time Frame
at 28 days after randomization
Title
Mean amplitude of sensor glucose excursions (MAGE)
Description
Mean amplitude of sensor glucose excursions (MAGE)
Time Frame
at 28 days after randomization
Title
Total number of adverse events
Description
Total number of adverse events
Time Frame
up to 60 days after randomization
Title
Number of Serious adverse events
Description
Number of Serious adverse events
Time Frame
up to 60 days after randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients after bariatric surgery (i.e. sleeve gastrectomy, Roux-en-Y gastric bypass, omega- loop bypass, biliopancreatic diversion) with documented hypoglycemia, i. e. < 3.0 mmol/l and at least 5 hypoglycemic episodes per week despite dietary modification
For women with child-bearing potential, willingness to use contraceptive measures adequate to prevent pregnancy during the study
Informed Consent as documented by signature
Exclusion Criteria:
Any type of diabetes mellitus according to ADA criteria
Intolerance to the study drug
Signs of current infection
Use of any drug therapy for postbariatric hypoglycemia apart from acarbose (all remaining drugs have to be discontinued four half-life times before screening phase)
Neutropenia (leukocyte count < 1.5 × 109/L or absolute neutrophil count (ANC) < 0.5 × 109/L)
Anemia (hemoglobin < 11 g/dL for males, < 10 g/dL for females)
Clinically significant kidney or liver disease (creatinine > 1.5 mg/dL, AST/ALT > 2 × ULN, alkaline phosphatase > 2 × ULN, or total bilirubin [tBili] > 1.5 × ULN)
Uncontrolled congestive heart failure
Uncontrolled malignant disease
Currently pregnant or breastfeeding
Known or suspected non-compliance, drug or alcohol abuse
Meeting the criteria for vulnerability (e.g. participants incapable of judgment or participants under tutelage)
Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.
Participation in another clinical trial using investigational drugs in the last 30 days or planned participation in the next 60 days
Previous enrolment into the current study,
Enrolment of the investigator, his/her family members, employees and other dependent persons
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marc Y Donath, Prof. Dr. med.
Phone
+41 61 265 25 25
Email
marc.donath@usb.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Matthias Hepprich, Dr. med.
Phone
+41 61 328 60 77
Email
matthias.hepprich@usb.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Y Donath, Prof. Dr. med.
Organizational Affiliation
University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc Y Donath, Prof. Dr. med.
Phone
+41 61 265 25 25
Email
marc.donath@usb.ch
First Name & Middle Initial & Last Name & Degree
Matthias Hepprich, Dr. med.
Phone
+41 61 328 60 77
Email
matthias.hepprich@usb.ch
First Name & Middle Initial & Last Name & Degree
Marc Y Donath, Prof. Dr. med.
First Name & Middle Initial & Last Name & Degree
Matthias Hepprich, Dr. med.
First Name & Middle Initial & Last Name & Degree
Justus Fischer
Facility Name
University Hospital Berne and Center of Bariatric Surgery Berne
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lia Bally, Prof. Dr. med.
Email
lia.bally@insel.ch
First Name & Middle Initial & Last Name & Degree
David Herzig, Dr. med.
Email
david.herzig@extern.insel.ch
First Name & Middle Initial & Last Name & Degree
Lia Bally, Prof. Dr. med.
First Name & Middle Initial & Last Name & Degree
David Herzig, Dr. med.
Facility Name
Cantonal Hospital Olten, Endocrine Outpatient Clinic
City
Olten
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gottfried Rudofsky, Prof. Dr. med.
Email
gottfried.rudofsky@spital.so.ch
First Name & Middle Initial & Last Name & Degree
Gottfried Rudofsky, Prof. Dr. med.
12. IPD Sharing Statement
Learn more about this trial
Empagliflozin for the Treatment of Postprandial Hypoglycemia
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