A Randomised, Double-blind, Placebo Controlled, Parallel Group, Multi-centre Trial in Adult Subjects With Newly Diagnosed Type 1 Diabetes Mellitus Investigating the Effect of Verapamil SR on Preservation of Beta-cell Function (Ver-A-T1D)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 136
- 试验地点
- 24
- 主要终点
- Area under the stimulated C-peptide response curve
研究概览
简要总结
This study has been set up within the framework of the INNODIA network. INNODIA is a global partnership between 31 academic institutions, 6 industrial partners, a small sized enterprise and 2 patient organizations, bringing their knowledge and experience together with one common goal: "To fight type 1 diabetes". (www.innodia.eu) The overall aim of INNODIA is to advance in a decisive way how to predict, stage, evaluate and prevent the onset and progression of type 1 diabetes (T1D).
For this, INNODIA has established a comprehensive and interdisciplinary network of clinical and basic scientists, who are leading experts in the field of T1D research in Europe and UK (United Kingdom), with complementary expertise from the areas of immunology, Beta-cell biology, biomarker research and T1D therapy, joining forces in a coordinated fashion with industry partners and two foundations, as well as with all major stakeholders in the process, including regulatory bodies and patients with T1D and their families.
详细描述
The study is a multicenter, randomized, double-blind, placebo-controlled study in volunteers with newly diagnosed diabetes mellitus type 1 (within 6 weeks after diagnosis).
The purpose of the clinical trial is to confirm the effect of 360mg Verapamil sustained release (SR) administered orally once daily (titrated over the first 3 months from 120 mg to 360 mg) on the preservation of beta-cell function measured as stimulated C-peptide after 12 months compared to placebo.
The study has a cross-over design and a duration of approximately 24 months, consisting of 3 telephone visits and 7 visits at the trial site. The duration of the treatment phase with verapamil is 12 months, and an additional (optional) follow-up visit will be carried out 12 months after completion of the study. The study procedures are identical in all 20 clinical centres across Europe and the UK.
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
Trial participants and research teams will be blinded to the treatment group for the duration of the trial. The double blinding will be achieved by providing verapamil SR identical placebo tablets.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have given written informed consent
- •Age ≥18 and <45 at consent
- •Must have a diagnosis of T1D of within 6 weeks duration at screening (date of the first insulin injection)
- •Must have at least one or more diabetes-related autoantibodies present at screening: GADA, IA-2A and/or ZnT8A
- •Must have fasting C-peptide levels ≥100 pmol/L measured at screening
- •Be willing to comply with intensive diabetes management
排除标准
- •Be immunodeficient or have clinically significant chronic lymphopenia: Leukopenia (< 3,000 leukocytes /µL), neutropenia (<1,500 neutrophils/µL), lymphopenia (<800 lymphocytes/µL), or thrombocytopenia (<100,000 platelets/µL)
- •Have active signs or symptoms of acute infection at the time of screening
- •Be currently pregnant or lactating, or anticipate getting pregnant during the 12 months study period
- •Require use of immunosuppressive agents including chronic use of systemic steroids
- •Have evidence of current or past human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection
- •Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, chronic obstructive pulmonary disease (COPD), sickle cell disease, neurological, or blood count abnormalities as judged by the investigator
- •Have a history of malignancies other than skin
- •History of liver insufficiency or laboratory evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal
- •History of renal insufficiency or evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal
- •Current or ongoing use of non-insulin pharmaceuticals that affect glycaemic control within prior 7 days of screening
- •Use of any other investigational drug in the previous 30 days and/or intent on using any investigational drug for the duration of the trial
- •Current use of Verapamil or other calcium channel blockers
- •Known hypersensitivity to Verapamil or to any of its excipients
- •Concomitant medication known for significantly inducing or inhibiting CYP3A4 and/or glycoprotein-P metabolism
- •Intake of grapefruit juice, licorice, St.John's Wort, cannabidiol, ginkgo biloba
- •Substrate intake of CYP3A4 and/or glycoprotein-P metabolism, as judged by the investigator
- •Hypotension (of less than 100mmHg systolic), sick sinus syndrome (except patients with a functioning artificial pacemaker), uncompensated heart failure or severe left ventricular dysfunction; marked bradycardia (less than 50 beats/minute), atrial flutter or atrial fibrillation in the presence of an accessory bypass tract (e.g. Wolff-Parkinson-White syndrome), hypertrophic cardiomyopathy, acute myocardial infarction, attenuated neuromuscular transmission (e.g. by myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy)
- •ECG second or third degree atrioventricular block; Incomplete branch block
- •Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results
- •Current use of ß-blockers
研究组 & 干预措施
Placebo
Eligible participants will be randomised into the placebo arm and receive instructions on frequency of administration (daily intake).
40 participants on the control arm are expected to complete the trial.
干预措施: Placebo (Drug)
Verapamil SR
Eligible participants will be randomised into the Verapamil SR arm and receive instructions on frequency of administration (daily intake). 80 participants on the experimental arm are expected to complete the trial.
干预措施: Verapamil SR 120 mg (Drug)
结局指标
主要结局
Area under the stimulated C-peptide response curve
时间窗: At 12 months
The primary objective is to determine the changes in stimulated C-peptide response during the first two hours of a mixed meal tolerance test (MMTT) at baseline and after 12 months for 360mg Verapamil SR administered orally once daily versus placebo.
次要结局
- Area under the stimulated C-peptide response curve(At 3, 6, 9 and 24 months)
- Fasting C-peptide(At 12 months)
- Proinsulin, Insulin, Pro-IAPP and Proglucagon secretion(At baseline and 3, 6, 9 and 12 months)
- DBS C-peptide(At baseline, week 4, week 8, and 3, 6, and 9 months)
- Change in HbA1c(Baseline, 12 and 24 months)
- Severe hypoglycaemic episodes(Baseline to 12 months)
- DKA(Baseline to 12 months)
- Change in insulin requirements(Baseline, 12 and 24 months)
- Change in T1D associated autoantibodies(Baseline to 12 months)
- Continous glucose monitoring (CGM)(At Baseline and every 2 weeks prior to each visit (week 4, week 8, and 3, 6, and 9 months))