The primary objective of this randomized trial is to test whether a treatment with canakinumab 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.
Postprandial hypoglycemia is a debilitating medical complication after bariatric surgery for which no approved pharmacological treatment exists. In a former study, the IL-1 receptor antagonist Anakinra statistically significantly reduced the number of symptomatic hypoglycemia. This randomized clinical trial is to directly evaluate clinical outcomes and patient-relevant benefits of treatment with the IL-1 receptor canakinumab over 28 days. The primary objective of this randomized trial is to test whether a treatment with canakinumab 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. For each subject, a maximum study duration of four months is anticipated with: screening visit 1 (1 h), screening phase (10-day screening phase for postprandial hypoglycemia using a blinded continuous glucose monitoring system (CGMS, Dexcom G6)), randomization/starting visit (visit 2, 1.5 h) followed by a 28 days intervention period with two additional study days (visit 3 and 4, 0.5 h, change of blinded continuous glucose monitoring system (CGFS sensor), diary documentation, adverse events) and end of treatment visit (visit 5). A follow-up visit will be done two months after the end of the treatment phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
56
Canakinumab (Ilaris®, Novartis Switzerland) will be used in the recommended standard dose of 150 mg subcutaneously once. Patients will be randomized at visit 2 = Baseline to either placebo (1 ml 0.9 % saline solution s.c.) or treatment with 1 ml 150 mg canakinumab solution s.c. in a 1:1 manner.
1 ml 0.9 % saline solution s.c. Patients will be randomized at visit 2 = Baseline to either placebo (1 ml 0.9 % saline solution s.c.) or treatment with 1 ml 150 mg canakinumab solution s.c. in a 1:1 manner.
University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism
Basel, Switzerland
RECRUITINGCantonal Hospital Olten, Division of Endocrinology
Olten, Switzerland
RECRUITINGChange in Health related quality of life (mental health)
Health related quality of life (mental health; as assessed by the SF-36 mental health component score; MCS). The lower the score the more disability.
Time frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Change in Health related quality of life (physical health)
Health related quality of life (physical health; as assessed by the SF-36 physical component score; PCS). The lower the score the more disability.
Time frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Number of Hypoglycemic events
Hypoglycemic events defined as glucose values below 3.0 mmol/l
Time frame: From Baseline (study day 1) to day 29 (-1 /+2 days)
Change in Postprandial Symptoms of hypoglycemia according to Edinburgh Hypoglycemia Scale (EHSS)
Postprandial Symptoms of hypoglycemia defined as acute onset of typical symptoms according to Edinburgh Hypoglycemia Scale. The EHSS is an instrument to evaluate patients' experiences of symptoms in a typical hypoglycemic episode. It comprises 11 symptoms divided into three domains-neuroglycopenic, autonomic, and malaise, which are evaluated by a 7-point Likert scale "1= Not at all, 7= Very severely". The postprandial period is defined as 3 hours following meal intake.
Time frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Change in Hypoglycemia unawareness (measured by modified Clarke Score)
The Clarke questionnaire consists of eight specific items characterizing awareness of hypoglycemia giving a total score of "0" to "7 (score ≥4 suggests inadequate hypoglycemia awareness; a score ≤2 suggests normal hypoglycemia awareness
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Time frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Change in Fear of hypoglycemia (measured on a scale of 0 to 10)
The fear of hypoglycemia will be assessed by using a 10-cm long visual analogue scale graded from "0 - no fear at all" to "10 - massive fear"
Time frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Time below range (TBR; % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)
Time below range (TBR; % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)
Time frame: From Baseline (study day 1) to day 29 (-1 /+2 days)
Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L
Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L
Time frame: From Baseline (study day 1) to day 29 (-1 /+2 days)
Pattern of sensor glucose
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 CanpHy-Study Version 1.2 of date 02.04.2022 Page 26 of 47 (calculated as the maximal rate of decrease over 20min in the postprandial period). The postprandial period is defined as 3 hours following meal intake.
Time frame: From Baseline (study day 1) to day 29 (-1 /+2 days)
Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)
Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)
Time frame: From Baseline (study day 1) to day 29 (-1 /+2 days)
Mean amplitude of sensor glucose excursions (MAGE)
Mean amplitude of sensor glucose excursions (MAGE)
Time frame: From Baseline (study day 1) to day 29 (-1 /+2 days)
Change in Body weight
Change in Body weight
Time frame: From Baseline (study day 1) to day 29 (-1 /+2 days)
Total adverse events
Total adverse events
Time frame: From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)
Serious adverse events
Number of Serious adverse events
Time frame: From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)