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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03200782
Recruitment Status : Completed
First Posted : June 27, 2017
Last Update Posted : October 24, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

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).

Condition or disease Intervention/treatment Phase
Postprandial Hypoglycemia Bariatric Surgery Late Dumping Syndrome Drug: Empagliflozin Drug: Anakinra Other: oral placebo (winthrop tablet) Other: subcutaneous placebo (0.67 ml of 0.9% sodium chloride) Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Diagnostic
Official Title: Postprandial Hypoglycemia in Patients After Bariatric Surgery With Empagliflozin and Anakinra - The Hypo-BEAR-Study
Actual Study Start Date : May 30, 2017
Actual Primary Completion Date : September 21, 2018
Actual Study Completion Date : September 21, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: 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
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

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'

Active Comparator: 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
Drug: Empagliflozin
Glucose lowering effect of empagliflozin for reducing the counter-regulatory glucose-lowering response

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'

Active Comparator: 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
Drug: 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




Primary Outcome Measures :
  1. Postprandial hypoglycemia in patients after bariatric surgery [ Time Frame: 6 hours ]
    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.


Secondary Outcome Measures :
  1. change of C-peptide [ Time Frame: 6 hours ]
    plasma level of c-peptide with anakinra or empagliflozin in comparison to placebo

  2. plasma level of IL-1Beta [ Time Frame: 6 hours ]
    plasma level of IL-1Beta with anakinra or empagliflozin in comparison to placebo

  3. plasma level of Glucagon-like Peptide1 (GLP1) [ Time Frame: 6 hours ]
    plasma level of GLP1 with anakinra or empagliflozin in comparison to placebo

  4. change of glucagon level [ Time Frame: 6 hours ]
    plasma level of glucagon with anakinra or empagliflozin in comparison to placebo

  5. changes in Edinburgh Hypoglycemia Scale [ Time Frame: 6 hours ]
    changes in Edinburgh Hypoglycemia Scale with anakinra or empagliflozin in comparison to placebo

  6. amount of glucose needed for restoring normoglycemia [ Time Frame: 6 hours ]
    amount (gramme) of glucose needed for restoring normoglycemia with anakinra or empagliflozin in comparison to placebo

  7. length of time needed for restoring normoglycemia [ Time Frame: 6 hours ]
    length of time (minutes) needed for restoring normoglycemia with anakinra or empagliflozin in comparison to placebo



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03200782


Locations
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Switzerland
University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism
Basel, Switzerland, 4056 Basel
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
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Principal Investigator: Marc Donath, MD, Prof. University Hopsital Basel
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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT03200782    
Other Study ID Numbers: EKNZ 2017-00689
First Posted: June 27, 2017    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Basel, Switzerland:
postprandial hypoglycemia
bariatric surgery
late dumping syndrome
anakinra
empagliflozin
SGLT2 inhibitor
IL-1Beta
IL1
Additional relevant MeSH terms:
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Dumping Syndrome
Hypoglycemia
Pathologic Processes
Glucose Metabolism Disorders
Metabolic Diseases
Postgastrectomy Syndromes
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Postoperative Complications
Empagliflozin
Interleukin 1 Receptor Antagonist Protein
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs
Antirheumatic Agents