Postprandial HypoglycemiaHypo-BEARNCT03200782
Postprandial Hypoglycemia in Patients After Bariatric Surgery With Empagliflozin and Anakinra - The Hypo-BEAR-Study
A study testing Empagliflozin and Anakinra in people with Postprandial Hypoglycemia and Bariatric Surgery, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postprandial Hypoglycemia, Bariatric Surgery, Late Dumping Syndrome
- What is being tested?
- Empagliflozin and Anakinra
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteSwitzerland
- Study dates
- 30 May 2017to 21 Sep 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism
Basel, 4056 Basel
About this study
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).
Read the 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.
- Being tested
- Empagliflozin, Anakinra, oral placebo (winthrop tablet), subcutaneous placebo (0.67 ml of 0.9% sodium chloride)
- Keywords
- postprandial hypoglycemia, bariatric surgery, late dumping syndrome, anakinra, empagliflozin, SGLT2 inhibitor, IL-1Beta, IL1
- Medical subject headings
- Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmpagliflozinDrug
Glucose lowering effect of empagliflozin for reducing the counter-regulatory glucose-lowering response
AnakinraDrug
IL-1Beta blockage effect on insulin secretion and thereby influencing postprandial glucose level
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
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'
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Anakinra; Other: oral placebo (winthrop tablet) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 hours
Secondary outcomes (7)
change of C-peptide
plasma level of c-peptide with anakinra or empagliflozin in comparison to placebo
Measured: 6 hours
plasma level of IL-1Beta
plasma level of IL-1Beta with anakinra or empagliflozin in comparison to placebo
Measured: 6 hours
plasma level of Glucagon-like Peptide1 (GLP1)
plasma level of GLP1 with anakinra or empagliflozin in comparison to placebo
Measured: 6 hours
change of glucagon level
plasma level of glucagon with anakinra or empagliflozin in comparison to placebo
Measured: 6 hours
changes in Edinburgh Hypoglycemia Scale
changes in Edinburgh Hypoglycemia Scale with anakinra or empagliflozin in comparison to placebo
Measured: 6 hours
amount of glucose needed for restoring normoglycemia
amount (gramme) of glucose needed for restoring normoglycemia with anakinra or empagliflozin in comparison to placebo
Measured: 6 hours
length of time needed for restoring normoglycemia
length of time (minutes) needed for restoring normoglycemia with anakinra or empagliflozin in comparison to placebo
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2017
- Study start30 May 2017
- Primary completion21 Sep 2018
- Study completion21 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Postprandial HypoglycemiaStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marc Donath, MD, Prof., Principal investigator, University Hopsital Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03200782
- Sponsor's protocol ID
- EKNZ 2017-00689
- Acronym
- Hypo-BEAR
- Status last verified
- Oct 2018
- First submitted
- 30 May 2017
- Last updated
- 24 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32197070
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Postprandial Hypoglycemia in Patients After Bariatric Surgery With Empagliflozin and Anakinra - The Hypo-BEAR-Study
- ClinicalTrials.gov ID
- NCT03200782
- Acronym / sponsor ID
- Hypo-BEAR / EKNZ 2017-00689
- Keywords
- postprandial hypoglycemia, bariatric surgery, late dumping syndrome, anakinra, empagliflozin, SGLT2 inhibitor, IL-1Beta, IL1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 30 May 2017 (actual)
- Primary completion
- 21 Sep 2018 (actual)
- Study completion
- 21 Sep 2018 (actual)
- First posted
- 27 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo-Placebo | Placebo comparator | Other: oral placebo (winthrop tablet), Other: subcutaneous placebo (0.67 ml of 0.9% sodium chloride)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 A Empagliflozin | Active comparator | Drug: Empagliflozin, Other: subcutaneous placebo (0.67 ml of 0.9% sodium chloride)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 |
| Investigational Drug B Anakinra | Active comparator | Drug: Anakinra, Other: oral placebo (winthrop tablet)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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmpagliflozinGlucose lowering effect of empagliflozin for reducing the counter-regulatory glucose-lowering response | Drug | Investigational Drug A Empagliflozin |
| AnakinraIL-1Beta blockage effect on insulin secretion and thereby influencing postprandial glucose level | Drug | Investigational Drug B Anakinra |
| 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 | Investigational Drug B Anakinra, Placebo-Placebo |
| 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' | Other | Investigational Drug A Empagliflozin, Placebo-Placebo |
Primary outcome
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.
7 secondary outcomes
change of C-peptide
Time frame: 6 hours
plasma level of IL-1Beta
Time frame: 6 hours
plasma level of Glucagon-like Peptide1 (GLP1)
Time frame: 6 hours
change of glucagon level
Time frame: 6 hours
changes in Edinburgh Hypoglycemia Scale
Time frame: 6 hours
amount of glucose needed for restoring normoglycemia
Time frame: 6 hours
length of time needed for restoring normoglycemia
Time frame: 6 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2018.
- Derived from this study: PubMed 32197070Hepprich 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Donath, MD, Prof. principal investigator
University Hopsital Basel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Empagliflozin and Anakinra in people with Postprandial Hypoglycemia and Bariatric Surgery, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postprandial hypoglycemia in patients after bariatric surgery (time frame: 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03200782, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2018.