EmpHy: Empagliflozin for the Treatment of Postprandial Hypoglycemia

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Recruiting

CT.gov ID

NCT05036317

Collaborator

Boehringer Ingelheim (Industry)

Enrollment

Locations

Arms

20.7

Anticipated Duration (Months)

20.7

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Postprandial Hypoglycemia	Drug: Empagliflozin (Jardiance®; Other: Placebo Control Intervention	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

62 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

1:1 randomized, placebo-controlled, parallel-group double-blind superiority trial1:1 randomized, placebo-controlled, parallel-group double-blind superiority trial

Masking:

Double (Participant, Investigator)

Masking Description:

Both subjects and investigators will be blinded.

Primary Purpose:

Treatment

Official Title:

Empagliflozin for the Treatment of Postprandial Hypoglycemia

Actual Study Start Date :

Mar 11, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Empagliflozin 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.	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.
Placebo Comparator: Placebo Placebo provided by Boehringer Ingelheim Switzerland. Per os once daily in the morning for 28 days.	Other: Placebo Control Intervention Placebo will be provided by Boehringer Ingelheim. It is identical to the interventional product apart from the active compound.

Arm

Intervention/Treatment

Experimental: Empagliflozin

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.

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.

Placebo Comparator: Placebo

Placebo provided by Boehringer Ingelheim Switzerland. Per os once daily in the morning for 28 days.

Other: Placebo Control Intervention

Placebo will be provided by Boehringer Ingelheim. It is identical to the interventional product apart from the active compound.

Outcome Measures

Primary Outcome Measures

Change in Quality of life (mental health; as assessed by the SF-36 mental health component score; MCS) [at baseline, at day 29 and at day 60 (+/- 10 days) after baseline]
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) [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). 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 [at 28 days after randomization]
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. [at 28 days after randomization]
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) [at 28 days after randomization]
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) [at 28 days after randomization]
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) [at 28 days after randomization]
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 [at 28 days after randomization]
Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L
Pattern of sensor glucose [at 28 days after randomization]
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 [at 28 days after randomization]
Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)
Mean amplitude of sensor glucose excursions (MAGE) [at 28 days after randomization]
Mean amplitude of sensor glucose excursions (MAGE)
Total number of adverse events [up to 60 days after randomization]
Total number of adverse events
Number of Serious adverse events [up to 60 days after randomization]
Number of Serious adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism	Basel	Switzerland	4031
2	University Hospital Bern and Center for Bariatric Surgery Berne	Bern	Switzerland	3011
3	Department of Endocrinology Cantonal Hospital Olten	Olten	Switzerland