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

Bariatric Surgery Clinical Trial

— Hypo-BEAR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03200782
• Other study ID #: EKNZ 2017-00689
• Status: Completed
• Phase: N/A
• Start date: May 30, 2017
• Est. completion date: September 21, 2018

Study information

• Verified date: October 2018
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 21, 2018
• Est. primary completion date: September 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bariatric Surgery
• Dumping Syndrome
• Hypoglycemia
• Late Dumping Syndrome
• Postprandial Hypoglycemia

Intervention

Drug:
• Empagliflozin
Glucose lowering effect of empagliflozin for reducing the counter-regulatory glucose-lowering response
• Anakinra
IL-1Beta blockage effect on insulin secretion and thereby influencing postprandial glucose level

Other:
• oral placebo (winthrop tablet)
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
• subcutaneous placebo (0.67 ml of 0.9% sodium chloride)
subcutaneous placebo (0.67 ml of 0.9% sodium chloride) will be administered in arm 'Placebo-Placebo' and arm 'drug: Empagliflozin'

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 hours
Secondary	change of C-peptide	plasma level of c-peptide with anakinra or empagliflozin in comparison to placebo	6 hours
Secondary	plasma level of IL-1Beta	plasma level of IL-1Beta with anakinra or empagliflozin in comparison to placebo	6 hours
Secondary	plasma level of Glucagon-like Peptide1 (GLP1)	plasma level of GLP1 with anakinra or empagliflozin in comparison to placebo	6 hours
Secondary	change of glucagon level	plasma level of glucagon with anakinra or empagliflozin in comparison to placebo	6 hours
Secondary	changes in Edinburgh Hypoglycemia Scale	changes in Edinburgh Hypoglycemia Scale with anakinra or empagliflozin in comparison to placebo	6 hours
Secondary	amount of glucose needed for restoring normoglycemia	amount (gramme) of glucose needed for restoring normoglycemia with anakinra or empagliflozin in comparison to placebo	6 hours
Secondary	length of time needed for restoring normoglycemia	length of time (minutes) needed for restoring normoglycemia with anakinra or empagliflozin in comparison to placebo	6 hours