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Canakinumab for the Treatment of Postprandial Hypoglycemia (CanpHy)

Primary Purpose

Postprandial Hypoglycemia

Status

Recruiting

Phase

Phase 3

Locations

Switzerland

Study Type

Interventional

Intervention

Canakinumab

Placebo (0.9% NaCl)

About this trial

This is an interventional treatment trial for Postprandial Hypoglycemia focused on measuring bariatric surgery, IL-1 receptor antagonist, postbariatric hypoglycemia, canakinumab, quality of life

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospital Basel, Division of Endocrinology, Diabetes and MetabolismRecruiting
Cantonal Hospital Olten, Division of Endocrinology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Study Intervention: Canakinumab

Control Intervention: Placebo (0.9% NaCl)

Arm Description

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.

Placebo: 1 ml of 0.9 % NaCl

Outcomes

Primary Outcome Measures

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.

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.

Number of Hypoglycemic events

Hypoglycemic events defined as glucose values below 3.0 mmol/l

Secondary Outcome Measures

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.

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

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 below range (TBR; % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)

Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L

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.

Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)

Mean amplitude of sensor glucose excursions (MAGE)

Change in Body weight

Total adverse events

Serious adverse events

Number of Serious adverse events

Full Information

NCT ID

NCT05401578

First Posted

May 23, 2022

Last Updated

May 10, 2023

Sponsor

University Hospital, Basel, Switzerland

1. Study Identification

Unique Protocol Identification Number

NCT05401578

Brief Title

Canakinumab for the Treatment of Postprandial Hypoglycemia

Acronym

CanpHy

Official Title

Canakinumab for the Treatment of Postprandial Hypoglycemia - CanpHy Study

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 17, 2023 (Actual)

Primary Completion Date

May 2024 (Anticipated)

Study Completion Date

May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Basel, Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Postprandial Hypoglycemia

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

National, multicenter, 1:1 randomized, placebo-controlled, parallel-group, double-blind superiority trial

Masking

ParticipantInvestigator

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.

Allocation

Randomized

Enrollment

56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Study Intervention: Canakinumab

Arm Type

Active Comparator

Arm Description

Arm Title

Control Intervention: Placebo (0.9% NaCl)

Arm Type

Placebo Comparator

Arm Description

Placebo: 1 ml of 0.9 % NaCl

Intervention Type

Drug

Intervention Name(s)

Canakinumab

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo (0.9% NaCl)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in Health related quality of life (mental health)

Description

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)

Title

Change in Health related quality of life (physical health)

Description

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)

Title

Number of Hypoglycemic events

Description

Hypoglycemic events defined as glucose values below 3.0 mmol/l

Time Frame

From Baseline (study day 1) to day 29 (-1 /+2 days)

Secondary Outcome Measure Information:

Title

Change in Postprandial Symptoms of hypoglycemia according to Edinburgh Hypoglycemia Scale (EHSS)

Description

Time Frame

At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)

Title

Change in Hypoglycemia unawareness (measured by modified Clarke Score)

Description

Time Frame

At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)

Title

Change in Fear of hypoglycemia (measured on a scale of 0 to 10)

Description

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)

Title

Time below range (TBR; % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)

Description

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)

Title

Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L

Description

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)

Title

Pattern of sensor glucose

Description

Time Frame

From Baseline (study day 1) to day 29 (-1 /+2 days)

Title

Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)

Description

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)

Title

Mean amplitude of sensor glucose excursions (MAGE)

Description

Mean amplitude of sensor glucose excursions (MAGE)

Time Frame

From Baseline (study day 1) to day 29 (-1 /+2 days)

Title

Change in Body weight

Description

Change in Body weight

Time Frame

From Baseline (study day 1) to day 29 (-1 /+2 days)

Title

Total adverse events

Description

Total adverse events

Time Frame

From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)

Title

Serious adverse events

Description

Number of Serious adverse events

Time Frame

From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Marc Y Donath, Prof. Dr. med.

Phone

+41 61 265 25 25

marc.donath@usb.ch

First Name & Middle Initial & Last Name or Official Title & Degree

Susanne Ruesch

Phone

+41 61 556 5655

susanne.ruesch@usb.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marc Y Donath, Prof. Dr. med.

Organizational Affiliation

University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marc Y Donath, Prof. Dr. med.

Phone

+41 61 265 25 25

marc.donath@usb.ch

First Name & Middle Initial & Last Name & Degree

Susanne Ruesch

Phone

+41 61 556 5655

susanne.ruesch@usb.ch

First Name & Middle Initial & Last Name & Degree

Marc Y Donath, Prof. Dr. med.

First Name & Middle Initial & Last Name & Degree

Jonathan Mudry, Dr. med.

First Name & Middle Initial & Last Name & Degree

Matthias Hepprich, Dr. med.

Facility Name

Cantonal Hospital Olten, Division of Endocrinology

City

Olten

ZIP/Postal Code

4600

Country

Switzerland

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Matthias Hepprich, Dr. med.

Phone

+41 61 328 60 77

matthias.hepprich@spital.so.ch

First Name & Middle Initial & Last Name & Degree

Matthias Hepprich, Dr. med.

12. IPD Sharing Statement

Learn more about this trial

Canakinumab for the Treatment of Postprandial Hypoglycemia

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