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Empagliflozin for the Treatment of Postprandial Hypoglycemia (EmpHy)

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ClinicalTrials.gov Identifier: NCT05036317
Recruitment Status : Recruiting
First Posted : September 5, 2021
Last Update Posted : September 14, 2021
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:
This randomized trial is to test whether a treatment with empagliflozin is superior to placebo in patients with postprandial hypoglycemia after bariatric surgery, that is if it improves health related quality of life (mentally or physically) or reduces the risk of hypoglycemic events.

Condition or disease Intervention/treatment Phase
Postprandial Hypoglycemia Drug: Empagliflozin (Jardiance®; Other: Placebo Control Intervention Phase 3

Detailed Description:

Postprandial hypoglycemia is a debilitating medical complication after bariatric surgery for which no approved pharmacological treatment exists. The prevalence of hypoglycemia in bariatric patients ranges from 0.5 % severe episodes up to 56 % and its symptoms range from asymptomatic to deleterious. This hypoglycemic condition is characterized by a rapid increase of plasma glucose after carbohydrate ingestion followed by an exaggerated hyperinsulinemic response. Hypoglycemia itself may lead to increased hunger, carbohydrate ingestion and following weight regain.

In a placebo-controlled, randomized, double-blind, crossover study, the SGLT2-inhibitor empagliflozin statistically significantly reduced the number of symptomatic hypoglycemia (2 vs. 7 symptomatic hypoglycemic episodes; p=0.013) compared to placebo after a mixed meal test in 12 patients after Roux-en-Y gastric bypass. Empagliflozin reduced the postprandial rise in glycemia and decreased subsequent insulin secretion, underlining the postulated mechanism of action.

This randomized trial is to test whether a treatment with empagliflozin is superior to placebo in patients with postprandial hypoglycemia after bariatric surgery, that is if it improves health related quality of life (mentally or physically) or reduces the risk of hypoglycemic events.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 1:1 randomized, placebo-controlled, parallel-group double-blind superiority trial
Masking: Double (Participant, Investigator)
Masking Description: Both subjects and investigators will be blinded.
Primary Purpose: Treatment
Official Title: Empagliflozin for the Treatment of Postprandial Hypoglycemia
Estimated Study Start Date : October 2021
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia

Arm Intervention/treatment
Experimental: Empagliflozin
Standard dose of empagliflozin (Jardiance®; Boehringer Ingelheim GmbH), i. e. 10 mg. Empagliflozin is an orally available inhibitor of SGLT2 and approved for the treatment of type 2 diabetes mellitus and will be given per os once daily in the morning for 28 days.
Drug: Empagliflozin (Jardiance®;
Each tablet contains the active substance of 10 mg empagliflozin as well as the adjuvant lactose-monohydrate and is taken orally once daily in the morning.

Placebo Comparator: Placebo
Placebo provided by Boehringer Ingelheim Switzerland. Per os once daily in the morning for 28 days.
Other: Placebo Control Intervention
Placebo will be provided by Boehringer Ingelheim. It is identical to the interventional product apart from the active compound.




Primary Outcome Measures :
  1. Change in Quality of life (mental health; as assessed by the SF-36 mental health component score; MCS) [ Time Frame: at baseline, at day 29 and at day 60 (+/- 10 days) after baseline ]
    Change in Quality of life (mental health; as assessed by the SF-36 mental health component. Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved.

  2. Change in Quality of life (physical health; as assessed by the SF-36 mental physical component score; PCS) [ Time Frame: at baseline, at day 29 and at day 60 (+/- 10 days) after baseline ]
    Change in Quality of life (physical health; as assessed by the SF-36 mental physical component score; PCS). Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved.

  3. Hypoglycemic events defined as glucose values below 3.0 mmol/l [ Time Frame: at 28 days after randomization ]
    Hypoglycemic events defined as glucose values below 3.0 mmol/l


Secondary Outcome Measures :
  1. Postprandial Symptoms of hypoglycemia defined as acute onset of typical symptoms according to Edinburgh Hypoglycemia Scale along with a decreasing blood glucose level. [ Time Frame: at 28 days after randomization ]
    Postprandial Symptoms of hypoglycemia defined as acute onset of typical symptoms according to Edinburgh Hypoglycemia Scale (7-point Likert scale (1 = not present, 7 = very intense)) along with a decreasing blood glucose level. The postprandial period is defined as 3 hours following meal intake.

  2. Hypoglycemia unawareness (measured by modified Clarke Score) [ Time Frame: at 28 days after randomization ]
    Hypoglycemia unawareness (measured by modified Clarke Score). The Clarke method comprises eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia. It also examines the glycemic threshold for, and symptomatic responses to, hypoglycemia. A score of four or more implies impaired awareness of hypoglycemia.

  3. Fear of hypoglycemia (measured on a scale of 0 to 10) [ Time Frame: at 28 days after randomization ]
    Fear of hypoglycemia (measured on a scale of 0 to 10)

  4. Time below range (TBR): % of sensor glucose readings and time between 3.0 and 3.8 mmol/L) [ Time Frame: at 28 days after randomization ]
    Time below range (TBR): % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)

  5. Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L [ Time Frame: at 28 days after randomization ]
    Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L

  6. Pattern of sensor glucose [ Time Frame: at 28 days after randomization ]
    Pattern of sensor glucose, defined as the slope of postprandial increase (calculated as the maximal rate of increase observed over 20min in the postprandial period) and decrease (calculated as the maximal rate of decrease over 20min in the postprandial period).

  7. Glycemic variability [ Time Frame: at 28 days after randomization ]
    Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)

  8. Mean amplitude of sensor glucose excursions (MAGE) [ Time Frame: at 28 days after randomization ]
    Mean amplitude of sensor glucose excursions (MAGE)

  9. Total number of adverse events [ Time Frame: up to 60 days after randomization ]
    Total number of adverse events

  10. Number of Serious adverse events [ Time Frame: up to 60 days after randomization ]
    Number of Serious adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 bariatric surgery (i.e. sleeve gastrectomy, Roux-en-Y gastric bypass, omega- loop bypass, biliopancreatic diversion) with documented hypoglycemia, i. e. < 3.0 mmol/l and at least 5 hypoglycemic episodes per week despite dietary modification
  • Age ≥ 18 years
  • For women with child-bearing potential, willingness to use contraceptive measures adequate to prevent pregnancy during the study
  • Informed Consent as documented by signature

Exclusion Criteria:

  • Any type of diabetes mellitus according to ADA criteria
  • Signs of current infection
  • Use of any drug therapy for postbariatric hypoglycemia apart from acarbose (all remaining drugs have to be discontinued four half-life times before screening phase)
  • 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, AST/ALT > 2 × ULN, alkaline phosphatase > 2 × ULN, or total bilirubin [tBili] > 1.5 × ULN)
  • Uncontrolled congestive heart failure
  • Uncontrolled malignant disease
  • Currently pregnant or breastfeeding
  • Known or suspected non-compliance, drug or alcohol abuse
  • Meeting the criteria for vulnerability (e.g. participants incapable of judgment or participants under tutelage)
  • Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.
  • Participation in another clinical trial using investigational drugs in the last 30 days or planned participation in the next 60 days
  • Previous enrolment into the current study,
  • Enrolment of the investigator, his/her family members, employees and other dependent persons

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): NCT05036317


Contacts
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Contact: Marc Y Donath, Prof. Dr. med. +41 61 265 25 25 marc.donath@usb.ch
Contact: Matthias Hepprich, Dr. med. +41 61 328 60 77 matthias.hepprich@usb.ch

Locations
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Switzerland
University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism Recruiting
Basel, Switzerland, 4031
Contact: Marc Y Donath, Prof. Dr. med.    +41 61 265 25 25    marc.donath@usb.ch   
Contact: Matthias Hepprich, Dr. med.    +41 61 328 60 77    matthias.hepprich@usb.ch   
Principal Investigator: Marc Y Donath, Prof. Dr. med.         
Sub-Investigator: Matthias Hepprich, Dr. med.         
Sub-Investigator: Jonathan Mudry         
University Hospital Bern and Center for Bariatric Surgery Berne Recruiting
Bern, Switzerland, 3011
Contact: Lia Bally, Prof. Dr. med.       lia.bally@insel.ch   
Principal Investigator: Lia Bally, Prof. Dr. med.         
Sub-Investigator: David Herzig, Dr. med.         
Department of Endocrinology Cantonal Hospital Olten Recruiting
Olten, Switzerland
Contact: Gottfried Rudofsky, Prof. Dr. med.       gottfried.rudofsky@spital.so.ch   
Principal Investigator: Gottfried Rudofsky, Prof. Dr. med.         
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Boehringer Ingelheim
Investigators
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Principal Investigator: Marc Y Donath, Prof. Dr. med. University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism
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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT05036317    
Other Study ID Numbers: 2021-00078; kt21Donath
First Posted: September 5, 2021    Key Record Dates
Last Update Posted: September 14, 2021
Last Verified: September 2021

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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:
Empagliflozin
bariatric surgery
hyperinsulinemic response
SGLT2-inhibitor
insulin secretion
postbariatric hypoglycemia
Additional relevant MeSH terms:
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Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Empagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs