Clinical trial NCT05401578: Canakinumab for the Treatment of Postprandial Hypoglycemia
Official title: Canakinumab for the Treatment of Postprandial Hypoglycemia - CanpHy Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Postprandial Hypoglycemia
Keywords: bariatric surgery
IL-1 receptor antagonist
postbariatric hypoglycemia
canakinumab
quality of life
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2022-06-02
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: National, multicenter, 1:1 randomized, placebo-controlled, parallel-group, double-blind superiority trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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
* 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
* Intolerance to the study drug
* Signs of current infection
* Any use of immunosuppressive medication
* 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 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

Primary outcomes:
measure: Change in Health related quality of life (mental health)
timeFrame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
measure: Change in Health related quality of life (physical health)
timeFrame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
measure: Number of Hypoglycemic events
timeFrame: From Baseline (study day 1) to day 29 (-1 /+2 days)
Secondary outcomes:
measure: Change in Postprandial Symptoms of hypoglycemia according to Edinburgh Hypoglycemia Scale (EHSS)
timeFrame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
measure: Change in Hypoglycemia unawareness (measured by modified Clarke Score)
timeFrame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
measure: Change in Fear of hypoglycemia (measured on a scale of 0 to 10)
timeFrame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
measure: Time below range (TBR; % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)
timeFrame: From Baseline (study day 1) to day 29 (-1 /+2 days)
measure: Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L
timeFrame: From Baseline (study day 1) to day 29 (-1 /+2 days)
measure: Pattern of sensor glucose
timeFrame: From Baseline (study day 1) to day 29 (-1 /+2 days)
measure: Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)
timeFrame: From Baseline (study day 1) to day 29 (-1 /+2 days)
measure: Mean amplitude of sensor glucose excursions (MAGE)
timeFrame: From Baseline (study day 1) to day 29 (-1 /+2 days)
measure: Change in Body weight
timeFrame: From Baseline (study day 1) to day 29 (-1 /+2 days)
measure: Total adverse events
timeFrame: From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)
measure: Serious adverse events
timeFrame: From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism
city: Olten
country: Switzerland
facility: Cantonal Hospital Olten, Division of Endocrinology
Study officials:
affiliation: University of Basel
name: Marc Y Donath, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: