Canakinumab for the Treatment of Postprandial Hypoglycemia - CanpHy Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 56
- 试验地点
- 2
- 主要终点
- Change in Health related quality of life (physical health)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Canakinumab (Drug)
Control Intervention: Placebo (0.9% NaCl)
Placebo: 1 ml of 0.9 % NaCl
干预措施: Placebo (0.9% NaCl) (Drug)
结局指标
主要结局
Change in Health related quality of life (physical health)
时间窗: 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.
Number of Hypoglycemic events
时间窗: From Baseline (study day 1) to day 29 (-1 /+2 days)
Hypoglycemic events defined as glucose values below 3.0 mmol/l
Change in Health related quality of life (mental health)
时间窗: 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.
次要结局
- Change in Hypoglycemia unawareness (measured by modified Clarke Score)(At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days))
- 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))
- Mean amplitude of sensor glucose excursions (MAGE)(From Baseline (study day 1) to day 29 (-1 /+2 days))
- Change in Body weight(From Baseline (study day 1) to day 29 (-1 /+2 days))
- Change in Postprandial Symptoms of hypoglycemia according to Edinburgh Hypoglycemia Scale (EHSS)(At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days))
- Total adverse events(From Baseline (study day 1) to Follow- up (day 90 +/- 11 days))
- Change in Fear of hypoglycemia (measured on a scale of 0 to 10)(At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days))
- Pattern of sensor glucose(From Baseline (study day 1) to day 29 (-1 /+2 days))
- Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)(From Baseline (study day 1) to day 29 (-1 /+2 days))
- Serious adverse events(From Baseline (study day 1) to Follow- up (day 90 +/- 11 days))
- 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))