Postprandial Hypoglycemia in Patients After Bariatric Surgery With Empagliflozin and Anakinra - The Hypo-BEAR-Study

N/ACompletedNCT03200782

University Hospital, Basel, Switzerland12 enrolled

Overview

The purpose of the study is to investigate whether hypoglycaemia observed after food intake in bariatric patients can be either influenced by an SGLT2 inhibitor, empagliflozin, or via inhibition of inflammation with an human interleukin-1 receptor antagonist (IL1-RA, anakinra).

Postprandial hypoglycemia also referred as late-dumping after bariatric surgery can be clinically asymptomatic but also life-threatening. The exact mechanisms leading to postprandial hypoglycemia are not fully understood and therapeutic options are limited and often accompanied with reduced life-quality and weight gain. In this study, prospective, randomly selected and double-blinded treatment is performed to investigate the effect on postprandial hypoglycemia. A total of 12 subjects participate in the study. After a screening date, three study dates will be performed. Participation in the study usually takes two weeks, but can also be extended to three weeks in individual cases. The University Hospital Basel will be the only test center in this study. In order to check whether the increase in blood glucose after food intake and subsequent excessive reaction of the body followed by hypoglycaemia patients receive either anakinra as a subcutaneous injection 3h or empagliflozin as a tablet 2 h before a liquid standardized test meal. On one study day only subcutaneous and oral placebo control will be used. At the beginning of each study date as well as at the time of the test meal several blood samples will be taken to evaluate blood glucose and blood glucose-influencing parameters (insulin / C-peptide, intestinal hormones, inflammatory parameters such as C-reactive protein, IL1beta and IL1-receptor agonist as well as macrophage and t-lymphocyte subpopulations) will be controlled. Questionnaires for dumping symptoms (Dumping Rating scale, Sigstad Score) and hypoglycemia testing with mini-mental test, stanford sleepiness scale and Edinburgh Hypoglycemia Scale will be performed repetitively.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

DOUBLE

Enrollment

Conditions

Postprandial Hypoglycemia Bariatric Surgery Late Dumping Syndrome

Interventions

EmpagliflozinDRUG

Glucose lowering effect of empagliflozin for reducing the counter-regulatory glucose-lowering response

AnakinraDRUG

IL-1Beta blockage effect on insulin secretion and thereby influencing postprandial glucose level

oral placebo (winthrop tablet)OTHER

subcutaneous placebo (0.67 ml of 0.9% sodium chloride) 3 hours before the test meal and an oral placebo (winthrop tablet) 2 hours before the test meal will be administered by an Independent nurse to the blinded patient

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients after roux-y-gastric bypass or biliopancreatic diversion with documented hypoglycemia, i. e. ≤ 2.5 mmol/l and hypoglycaemic symptoms. * For subjects with reproductive potential, willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study Exclusion Criteria: * Signs of current infection * Use of any investigational drug in the last four weeks prior to enrolment * Use of any anti-diabetic drugs * adrenal insufficiency and/or substitution with glucocorticoids * 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, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 2 × ULN, alkaline phosphatase \> 2 × ULN, or total bilirubin \[tBili\] \> 1.5 × ULN) * Current immunosuppressive treatment or documented immunodeficiency * Uncontrolled congestive heart failure * Uncontrolled malignant disease * Currently pregnant or breastfeeding * known lactose intolerance

Locations (1)

University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism

Basel, Switzerland

Outcomes

Primary Outcomes

Postprandial hypoglycemia in patients after bariatric surgery

To assess whether empagliflozin or anakinra compared to placebo reduce the severity of hypoglycemia (i.e. change of blood glucose level in mmol/l) following a mixed-meal in patients after bariatric surgery.

Time frame: 6 hours

Secondary Outcomes

change of C-peptide

plasma level of c-peptide with anakinra or empagliflozin in comparison to placebo

Time frame: 6 hours

plasma level of IL-1Beta

plasma level of IL-1Beta with anakinra or empagliflozin in comparison to placebo

Time frame: 6 hours

plasma level of Glucagon-like Peptide1 (GLP1)

plasma level of GLP1 with anakinra or empagliflozin in comparison to placebo

Time frame: 6 hours

change of glucagon level

plasma level of glucagon with anakinra or empagliflozin in comparison to placebo

Time frame: 6 hours

changes in Edinburgh Hypoglycemia Scale

changes in Edinburgh Hypoglycemia Scale with anakinra or empagliflozin in comparison to placebo

Time frame: 6 hours

amount of glucose needed for restoring normoglycemia

amount (gramme) of glucose needed for restoring normoglycemia with anakinra or empagliflozin in comparison to placebo

Time frame: 6 hours

length of time needed for restoring normoglycemia

Data from ClinicalTrials.gov

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