Postprandial hyperinsulinemic hypoglycaemia (PHH) typically occurs years after bariatric surgery and one to three hours after a carbohydrate-rich meal. It is caused by rapid gastric emptying of undigested carbohydrates leading to high plasma glucose concentrations and increased incretin release which results in hyperinsulinemia and finally hypoglycaemia. Patients may suffer from fatigue, weakness, confusion, hunger, syncope, perspiration, palpitations or tremor.
Conditions
Interventions
Trade Name: Jardiance
Product Name: Jardiance
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Empagliflozin
CAS Number: 864070-44-0
Other descriptive name: EMPAGLIFLOZIN
Concentration uni
Sponsors
Verein zur Förderung der Wissenschaft und Forschung an der 1.Med. Abteilung der Krankenanstalt Rudolfstiftung
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: >= 18 years, 1 year, No reported hypoglycemic episodes before bariatric surgery, Symptoms of PHH after bariatric surgery Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: diabetes mellitus type 1, type 2 or HbA1c = 6.5% or use anti-diabetic drugs or insulin, Use of any drug to treat PHH in the last four weeks (acarbose etc.), Have a current infection, anamnestic necrotising fasciitis, Follow a ketogenic diet, impaired renal function with a eGFR = 60 ml/min/m², recurrent urinary tract infections (= 2 episodes during the last year), pyelonephritis (=1 episode during the last 5 years), urosepsis (=1 episode during the last 5 years), Known or suspected hypersensitivity to trial product(s) or related products, Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method, Have diagnosed insulinoma, Had reoperation or revision of bariatric surgery , severe gastroparesis, BMI = 18.5 kg/m², severe cardiovascular disease with any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 90 days prior to the day of screening, Subjects presently classified as being in New York Heart Association Class IV, Have acute or chronic hepatitis, signs or symptoms of any other liver disease, or an alanine transaminase (ALT) level =3.0 above the upper limit of normal (ULN) for the reference range, as determined by the central laboratory, Have a history of an active or untreated malignancy, or are in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years, Have a history of any other condition (such as known drug or alcohol abuse or psychiatric disorder) that, in the opinion of the investigator, may preclude the patient from following and completing the protocol, Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study, Have participated, within the last 30 days in a clinical trial involving an investigational product. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer), should have passed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective is to assess the efficacy of empagliflozin compared to placebo. It is evaluated whether empagliflozin, as compared to placebo, reduce the frequency and severity of hypoglycaemic episodes in post-bariatric patients suffering from PHH. Therefore, data from CGM, OGTT and MMTT are used. Effects of empagliflozin, as compared to placebo, concerning nadir plasma glucose levels, postprandial plasma peak glucose levels, plasma c-peptide levels and plasma insulin levels will be evaluated. Length of time and amount of glucose needed to restore normoglycaemia will be examined. ;Secondary Objective: Impact of treatment with empagliflozin on symptoms of PHH will be evaluated by comparing scores of Edinburgh Hypoglycemia Scale, Stanford Sleepiness Scale and Sigstad’s Scoring System between baseline and treatment period. Furthermore, the influence of individual characteristics such as sex, age, insulin sensitivity, BMI, comorbidities and concomitant medications on the occurrence of hypoglycemic episodes under a treatment with empagliflozin will be regarded. Tolerability of both study drugs regarding side effects will be evaluated. ;Primary end point(s): frequency and severity of hypoglycemic episodes after 12 weeks of intervention with empagliflozin or placebo, Primary efficacy measures will be evaluated after 12 weeks of treatment with study drug: •Data from CGM; Time in range [27]: Time below range (TBR): % of readings and time 54–69 mg/dL – Level 1 Time below range (TBR): % of readings and time 250 mg/dL – Level 2 Time above range (TAR): %of readings and time 181–250 mg/dL – Level 1 •Data from OGTT/MMTT: Nadir plasma glucose levels after OGTT/MMTT Peak plasma glucose levels after OGTT/MMTT Plasma C-peptide levels after OGTT/MMTT Plasma insulin levels after OGTT/MMTT Nadir GLP-1 levels after OGTT/MMTT Maximum GLP-1 levels after OGTT/MMTT AUC values for GLP-1 levels after OGTT/MMTT •Rescue glucose needed for hypoglycaemic episodes (1 BE = 12 g c | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy measures will be evaluated after 12 weeks of treatment: • Symptoms of PHH objectified by Edinburgh Hypoglycemia Scale, Stanford Sleepiness Scale and Sigstad’s Scoring System • Influence of individual characteristics & anthropometric data on hypoglycaemic episodes (sex, age, weight, BMI, comorbidities, concomitant medications) • Tolerability of empagliflozine (number of AE, f.ex. number of genitourinary tract infections);Timepoint(s) of evaluation of this end point: The endpoint will be evaluated after 12 weeks | — |
Countries
Austria
Contacts
Public ContactDr. Bernhard Ludvik
Verein zur Förderung der Wissenschaft und Forschung an der 1.Med. Abteilung der Krankenanstalt Rudolfstiftung
Outcome results
None listed