Clinical trial NCT03200782: Postprandial Hypoglycemia in Patients After Bariatric Surgery With Empagliflozin and Anakinra - The Hypo-BEAR-Study
Official title: Postprandial Hypoglycemia in Patients After Bariatric Surgery With Empagliflozin and Anakinra - The Hypo-BEAR-Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postprandial Hypoglycemia
Bariatric Surgery
Late Dumping Syndrome
Keywords: postprandial hypoglycemia
bariatric surgery
late dumping syndrome
anakinra
empagliflozin
SGLT2 inhibitor
IL-1Beta
IL1
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2017-06-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Postprandial hypoglycemia in patients after bariatric surgery
timeFrame: 6 hours
Secondary outcomes:
measure: change of C-peptide
timeFrame: 6 hours
measure: plasma level of IL-1Beta
timeFrame: 6 hours
measure: plasma level of Glucagon-like Peptide1 (GLP1)
timeFrame: 6 hours
measure: change of glucagon level
timeFrame: 6 hours
measure: changes in Edinburgh Hypoglycemia Scale
timeFrame: 6 hours
measure: amount of glucose needed for restoring normoglycemia
timeFrame: 6 hours
measure: length of time needed for restoring normoglycemia
timeFrame: 6 hours
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism
Study officials:
affiliation: University Hopsital Basel
name: Marc Donath, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hepprich M, Wiedemann SJ, Schelker BL, Trinh B, Starkle A, Geigges M, Loliger J, Boni-Schnetzler M, Rudofsky G, Donath MY. Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1beta. Cell Metab. 2020 Apr 7;31(4):699-709.e5. doi: 10.1016/j.cmet.2020.02.013. Epub 2020 Mar 19.