Clinical trial NCT05036317: Empagliflozin for the Treatment of Postprandial Hypoglycemia
Official title: Empagliflozin for the Treatment of Postprandial Hypoglycemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Postprandial Hypoglycemia
Keywords: Empagliflozin
bariatric surgery
hyperinsulinemic response
SGLT2-inhibitor
insulin secretion
postbariatric hypoglycemia
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2021-09-05
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomized, placebo-controlled, parallel-group double-blind superiority trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Quality of life (mental health; as assessed by the SF-36 mental health component score; MCS)
timeFrame: at baseline, at day 29 and at day 60 (+/- 10 days) after baseline
measure: Change in Quality of life (physical health; as assessed by the SF-36 mental physical component score; PCS)
timeFrame: at baseline, at day 29 and at day 60 (+/- 10 days) after baseline
measure: Hypoglycemic events defined as glucose values below 3.0 mmol/l
timeFrame: at 28 days after randomization
Secondary outcomes:
measure: Postprandial Symptoms of hypoglycemia defined as acute onset of typical symptoms according to Edinburgh Hypoglycemia Scale along with a decreasing blood glucose level.
timeFrame: at 28 days after randomization
measure: Hypoglycemia unawareness (measured by modified Clarke Score)
timeFrame: at 28 days after randomization
measure: Fear of hypoglycemia (measured on a scale of 0 to 10)
timeFrame: at 28 days after randomization
measure: Time below range (TBR): % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)
timeFrame: at 28 days after randomization
measure: Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L
timeFrame: at 28 days after randomization
measure: Pattern of sensor glucose
timeFrame: at 28 days after randomization
measure: Glycemic variability
timeFrame: at 28 days after randomization
measure: Mean amplitude of sensor glucose excursions (MAGE)
timeFrame: at 28 days after randomization
measure: Total number of adverse events
timeFrame: up to 60 days after randomization
measure: Number of Serious adverse events
timeFrame: up to 60 days after randomization
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism
city: Bern
country: Switzerland
facility: University Hospital Berne and Center of Bariatric Surgery Berne
city: Olten
country: Switzerland
facility: Cantonal Hospital Olten, Endocrine Outpatient Clinic
Study officials:
affiliation: University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism
name: Marc Y Donath, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: