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

NCT ID: NCT03200782

Last Updated: 2018-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-30
• Study Completion Date: 2018-09-21

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.

Conditions

Postprandial Hypoglycemia; Bariatric Surgery; Late Dumping Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: DOUBLE

Study Groups

Placebo-Placebo

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

Group Type: PLACEBO_COMPARATOR

oral placebo (winthrop tablet)

Intervention Type: 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

subcutaneous placebo (0.67 ml of 0.9% sodium chloride)

Intervention Type: OTHER

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

Investigational Drug A Empagliflozin

subcutaneous placebo (0.67 ml of 0.9% sodium chloride) 3 hours before the test meal and an 10mg of empagliflozin 2 hours before the test meal will be administered by an independent nurse to the blinded patient

Group Type: ACTIVE_COMPARATOR

Empagliflozin

Intervention Type: DRUG

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

subcutaneous placebo (0.67 ml of 0.9% sodium chloride)

Intervention Type: OTHER

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

Investigational Drug B Anakinra

subcutaneous injection of 100mg anakinra 3 hours before the test meal and an oral placebo (winthrop tablet)before the test meal will be administered by an Independent nurse to the blinded patient

Group Type: ACTIVE_COMPARATOR

Anakinra

Intervention Type: DRUG

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

oral placebo (winthrop tablet)

Intervention Type: 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

Interventions

Empagliflozin

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

Intervention Type: DRUG

Anakinra

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

Intervention Type: DRUG

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

Intervention Type: OTHER

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'

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Donath, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Hopsital Basel

Locations

University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism

Basel, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 32197070 (View on PubMed)

Other Identifiers

EKNZ 2017-00689

Identifier Type: -

Identifier Source: org_study_id