Canakinumab for the Treatment of Postprandial Hypoglycemia

Официальное название

Canakinumab for the Treatment of Postprandial Hypoglycemia - CanpHy Study

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Change in Health related quality of life (mental health) [Срок оценки: 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) [Срок оценки: At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)]
• Number of Hypoglycemic events [Срок оценки: From Baseline (study day 1) to day 29 (-1 /+2 days)]

Вторичные конечные точки (11)

• Change in Postprandial Symptoms of hypoglycemia according to Edinburgh Hypoglycemia Scale (EHSS) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: From Baseline (study day 1) to day 29 (-1 /+2 days)]
• Pattern of sensor glucose [Срок оценки: From Baseline (study day 1) to day 29 (-1 /+2 days)]
• Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose) [Срок оценки: From Baseline (study day 1) to day 29 (-1 /+2 days)]
• Mean amplitude of sensor glucose excursions (MAGE) [Срок оценки: From Baseline (study day 1) to day 29 (-1 /+2 days)]
• Change in Body weight [Срок оценки: From Baseline (study day 1) to day 29 (-1 /+2 days)]
• Total adverse events [Срок оценки: From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)]
• Serious adverse events [Срок оценки: From Baseline (study day 1) to Follow- up (day 90 +/- 11 days)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Швейцария · 2 центра

• University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism — Basel
• Cantonal Hospital Olten, Division of Endocrinology — Olten

Идентификаторы

NCT: NCT05401578 · 2021-02325; kt21Donath2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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