Canakinumab for the Treatment of Postprandial Hypoglycemia (CanpHy)

• ClinicalTrials.gov Identifier: NCT05401578
• Recruitment Status: Recruiting
• First Posted: June 2, 2022
• Last Update Posted: May 11, 2023
• Sponsor: University Hospital, Basel, Switzerland
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Postprandial Hypoglycemia	Drug: Canakinumab; Drug: Placebo (0.9% NaCl)	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: National, multicenter, 1:1 randomized, placebo-controlled, parallel-group, double-blind superiority trial
• Masking: Double (Participant, Investigator)
• Masking Description: Both subjects and investigators will be blinded. A nurse independent of the research group will be responsible for treatment blinding and preparation of trial drugs throughout the study.
• Primary Purpose: Treatment
• Official Title: Canakinumab for the Treatment of Postprandial Hypoglycemia - CanpHy Study
• Actual Study Start Date: April 17, 2023
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: May 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Study Intervention: Canakinumab; Standard dose of canakinumab (Ilaris®; Novartis Switzerland), i. e. 150 mg subcutaneously. Canakinumab (Ilaris®, Novartis) is a recombinant, human monoclonal IgG1/kappa antibody inhibiting IL-1β by neutralizing its biological activity through binding to the IL-1 receptor.	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 Comparator: Control Intervention: Placebo (0.9% NaCl); Placebo: 1 ml of 0.9 % NaCl	Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in Health related quality of life (mental health) [ Time Frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days) ]
   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.
2. Change in Health related quality of life (physical health) [ Time Frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days) ]
   Health related quality of life (physical health; as assessed by the SF-36 physical component score; PCS). The lower the score the more disability.
3. Number of Hypoglycemic events [ Time Frame: From Baseline (study day 1) to day 29 (-1 /+2 days) ]
   Hypoglycemic events defined as glucose values below 3.0 mmol/l

Secondary Outcome Measures :

1. Change in Postprandial Symptoms of hypoglycemia according to Edinburgh Hypoglycemia Scale (EHSS) [ Time Frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days) ]
   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.
2. Change in Hypoglycemia unawareness (measured by modified Clarke Score) [ Time Frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days) ]
   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
3. Change in Fear of hypoglycemia (measured on a scale of 0 to 10) [ Time Frame: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days) ]
   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"
4. 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 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: 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
6. Pattern of sensor glucose [ Time Frame: From Baseline (study day 1) to day 29 (-1 /+2 days) ]
   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.
7. 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) ]
   Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)
8. Mean amplitude of sensor glucose excursions (MAGE) [ Time Frame: From Baseline (study day 1) to day 29 (-1 /+2 days) ]
   Mean amplitude of sensor glucose excursions (MAGE)
9. Change in Body weight [ Time Frame: From Baseline (study day 1) to day 29 (-1 /+2 days) ]
   Change in Body weight
10. Total adverse events [ Time Frame: From Baseline (study day 1) to Follow- up (day 90 +/- 11 days) ]
    Total adverse events
11. Serious adverse events [ Time Frame: From Baseline (study day 1) to Follow- up (day 90 +/- 11 days) ]
    Number of Serious adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (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
• 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

Contacts and Locations

Contacts

Contact: Marc Y Donath, Prof. Dr. med.; +41 61 265 25 25; marc.donath@usb.ch

Contact: Susanne Ruesch; +41 61 556 5655; susanne.ruesch@usb.ch

Locations

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: Susanne Ruesch +41 61 556 5655 susanne.ruesch@usb.ch

Principal Investigator: Marc Y Donath, Prof. Dr. med.

Sub-Investigator: Jonathan Mudry, Dr. med.

Sub-Investigator: Matthias Hepprich, Dr. med.

Cantonal Hospital Olten, Division of Endocrinology; Not yet recruiting

Olten, Switzerland, 4600

Contact: Matthias Hepprich, Dr. med. +41 61 328 60 77 matthias.hepprich@spital.so.ch

Principal Investigator: Matthias Hepprich, Dr. med.

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Investigators

• Principal Investigator: Marc Y Donath, Prof. Dr. med.; University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism

More Information

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT05401578
• Other Study ID Numbers: 2021-02325; kt21Donath2
• First Posted: June 2, 2022
• Last Update Posted: May 11, 2023
• Last Verified: May 2023

• 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:

bariatric surgery; IL-1 receptor antagonist; postbariatric hypoglycemia; canakinumab; quality of life

Additional relevant MeSH terms:

Hypoglycemia; Glucose Metabolism Disorders; Metabolic Diseases