Canakinumab for the Treatment of Postprandial Hypoglycemia

Postprandial Hypoglycemia Clinical Trial

— CanpHy  

Official title:

Canakinumab for the Treatment of Postprandial Hypoglycemia - CanpHy Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05401578
• Other study ID #: 2021-02325; kt21Donath2
• Status: Recruiting
• Phase: Phase 3
• Start date: April 17, 2023
• Est. completion date: May 2024

Study information

• Verified date: May 2023
• Source: University Hospital, Basel, Switzerland
• Contact: Marc Y Donath, Prof. Dr. med.
• Phone: +41 61 265 25 25
• Email: marc.donath[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypoglycemia
• Postprandial Hypoglycemia

Intervention

Drug:
• Canakinumab
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.
• Placebo (0.9% NaCl)
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.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism	Basel
Switzerland	Cantonal Hospital Olten, Division of Endocrinology	Olten

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change 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.	At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Primary	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.	At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Primary	Number of Hypoglycemic events	Hypoglycemic events defined as glucose values below 3.0 mmol/l	From Baseline (study day 1) to day 29 (-1 /+2 days)
Secondary	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.	At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Secondary	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	At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Secondary	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"	At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)
Secondary	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)	From Baseline (study day 1) to day 29 (-1 /+2 days)
Secondary	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	From Baseline (study day 1) to day 29 (-1 /+2 days)
Secondary	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.	From Baseline (study day 1) to day 29 (-1 /+2 days)
Secondary	Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)	Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)	From Baseline (study day 1) to day 29 (-1 /+2 days)
Secondary	Mean amplitude of sensor glucose excursions (MAGE)	Mean amplitude of sensor glucose excursions (MAGE)	From Baseline (study day 1) to day 29 (-1 /+2 days)
Secondary	Change in Body weight	Change in Body weight	From Baseline (study day 1) to day 29 (-1 /+2 days)
Secondary	Total adverse events	Total adverse events	From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)
Secondary	Serious adverse events	Number of Serious adverse events	From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)