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

NCT03200782 | Completed DMC

• 1 other identifier: EKNZ 2017-00689
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

Postprandial Hypoglycemia; Bariatric Surgery; Late Dumping Syndrome

Keywords

postprandial hypoglycemia; bariatric surgery; late dumping syndrome; anakinra; empagliflozin; SGLT2 inhibitor; IL-1Beta; IL1

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• change of C-peptide

  6 hours

• plasma level of IL-1Beta

  6 hours

• plasma level of Glucagon-like Peptide1 (GLP1)

  6 hours

• change of glucagon level

  6 hours

• changes in Edinburgh Hypoglycemia Scale

  6 hours

Study Arms (3)

Placebo-Placebo

PLACEBO COMPARATOR

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

Other: oral placebo (winthrop tablet); Other: subcutaneous placebo (0.67 ml of 0.9% sodium chloride)

Investigational Drug A Empagliflozin

ACTIVE COMPARATOR

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

Drug: Empagliflozin; Other: subcutaneous placebo (0.67 ml of 0.9% sodium chloride)

Investigational Drug B Anakinra

ACTIVE COMPARATOR

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

Drug: Anakinra; Other: oral placebo (winthrop tablet)

Interventions

Empagliflozin DRUG

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

Investigational Drug A Empagliflozin

Anakinra DRUG

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

Investigational Drug B Anakinra

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

Investigational Drug B Anakinra; Placebo-Placebo

subcutaneous placebo (0.67 ml of 0.9% sodium chloride) 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; Placebo-Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism

Basel, 4056 Basel, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 32197070 DERIVED

MeSH Terms

Conditions

Hypoglycemia

Interventions

empagliflozin; Interleukin 1 Receptor Antagonist Protein; Sodium Chloride

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Marc Donath, MD, Prof.

  University Hopsital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 27, 2017
• Study Start: May 30, 2017
• Primary Completion: September 21, 2018
• Study Completion: September 21, 2018
• Last Updated: October 24, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)