Empagliflozin for the Treatment of Postprandial Hypoglycemia

Postprandial Hypoglycemia Clinical Trial

— EmpHy  

Official title:

Empagliflozin for the Treatment of Postprandial Hypoglycemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05036317
• Other study ID #: 2021-00078; kt21Donath
• Status: Recruiting
• Phase: Phase 3
• Start date: March 11, 2022
• Est. completion date: December 2023

Study information

• Verified date: April 2023
• Source: University Hospital, Basel, Switzerland
• Contact: Marc Y Donath, Prof. Dr. med.
• Phone: +41 61 265 25 25
• Email: marc.donath[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypoglycemia
• Postprandial Hypoglycemia

Intervention

Drug:
• Empagliflozin (Jardiance®;
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.

Other:
• Placebo Control Intervention
Placebo will be provided by Boehringer Ingelheim. It is identical to the interventional product apart from the active compound.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism	Basel
Switzerland	University Hospital Berne and Center of Bariatric Surgery Berne	Bern
Switzerland	Cantonal Hospital Olten, Endocrine Outpatient Clinic	Olten

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Boehringer Ingelheim

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Secondary	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.	at 28 days after randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Glycemic variability	Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)	at 28 days after randomization
Secondary	Mean amplitude of sensor glucose excursions (MAGE)	Mean amplitude of sensor glucose excursions (MAGE)	at 28 days after randomization
Secondary	Total number of adverse events	Total number of adverse events	up to 60 days after randomization
Secondary	Number of Serious adverse events	Number of Serious adverse events	up to 60 days after randomization