Evaluation of the Efficacy of Rapamycin and a Dipeptidyl Peptidase-4 Inhibitor (Vildagliptin) in Improving Beta Cell Function in Type 1 Diabetes of Long Duration, a Perspective Randomized Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Change from Baseline C-peptide after the MMTT
研究概览
简要总结
This study is a phase 2, single-center, prospective, randomized, double-blind, placebo-controlled, 3-arm parallel group (1:1:1) intervention trial to determine the efficacy of 4 weeks rapamycin treatment and 4 weeks rapamycin treatment plus 3 months vildagliptin treatment versus placebo in increasing endogenous insulin production and correcting glycemic lability. It will involve 60 patients with long standing type 1 diabetes (T1D). Patients will receive for one month placebo (Group 1), rapamycin plus placebo (Group 2), or rapamycin plus Vildagliptin (Group 3). Rapamycin will be administered at an initial dose 0.2 mg/kg orally on day 0 followed by 0.1 mg/kg/die (target trough levels: 8-10 ng/ml). Vildagliptin will be administered at a dose of 50 mg x2/die starting from day 0. After 4 weeks of treatment (period A), patients will discontinue rapamycin or relevant placebo treatment, but continue Vildagliptin or placebo for a further 8 weeks and be monitored over this period (period B).
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, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged >18 years, inclusive
- •Clinical history compatible with T1D with onset of disease at < 40 years of age, insulin dependence for ≥ 5 years at the time of enrolment
- •C-peptide concentrations under the threshold of preserved beta cell function: fasting C peptide <0.23 ng/ml
- •Detectable fasting proinsulin concentrations (>0.5 pmol/l)
- •Ability to provide written informed consent
- •Mentally stable and able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations
排除标准
- •Body mass index (BMI) >30 kg/m2 or patient with body weight ≤40kg;
- •Insulin requirement >1.0 IU/kg/day or <10 U/day;
- •HbA1c >11% (normal value: 3.5-6.0%) at the time of enrolment
- •estimated glomerular filtration rate <60 mL/min/1.73m2 calculated using the subject's measured serum creatinine and the Modification of Diet in Renal Disease [MDRD] study estimation formula)
- •Presence or history of macroalbuminuria (>300mg/g creatinine)
- •For female subjects: positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation of treatment
- •Active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB) as determined by a positive skin test or clinical presentation, or under treatment for suspected TB
- •Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
- •Lymphopenia (<1,000/μL), neutropenia (<1,500/μL), or thrombocytopenia (platelets <100,000/μL).
- •Severe unremitting diarrhea, vomiting or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications
- •Any medical condition that will interfere with safe participation in the trial;
- •Any immunosuppressive treatment at the time of enrollment.
- •Allergy to active ingredients or to any of excipients
研究组 & 干预措施
Group 1: Placebo
Eligible participants will be randomized to one of three treatment arms. In this arm patients will received placebo x 2 placebo (Group 1) After 4 weeks of treatment, patients will discontinue relevant placebo treatment, but continue the second placebo for a further 8 weeks
干预措施: Placebo 1 (Drug)
Group 1: Placebo
Eligible participants will be randomized to one of three treatment arms. In this arm patients will received placebo x 2 placebo (Group 1) After 4 weeks of treatment, patients will discontinue relevant placebo treatment, but continue the second placebo for a further 8 weeks
干预措施: Placebo 2 (Drug)
Group 2: Rapamycin plus Placebo
Eligible participants will be randomized to one of three treatment arms. In this arm patients will received rapamycin plus placebo. After 4 weeks of treatment, patients will discontinue rapamycin, but continue the second placebo for a further 8 weeks
干预措施: rapamycin (Drug)
Group 3: Rapamycin plus Vildagliptin
Eligible participants will be randomized to one of three treatment arms. In this arm patients will received rapamycin plus vildagliptin. After 4 weeks of treatment, patients will discontinue rapamycin , but continue Vildagliptin o for a further 8 weeks
干预措施: Vildagliptin (Drug)
Group 3: Rapamycin plus Vildagliptin
Eligible participants will be randomized to one of three treatment arms. In this arm patients will received rapamycin plus vildagliptin. After 4 weeks of treatment, patients will discontinue rapamycin , but continue Vildagliptin o for a further 8 weeks
干预措施: rapamycin (Drug)
Group 2: Rapamycin plus Placebo
Eligible participants will be randomized to one of three treatment arms. In this arm patients will received rapamycin plus placebo. After 4 weeks of treatment, patients will discontinue rapamycin, but continue the second placebo for a further 8 weeks
干预措施: Vildagliptin (Drug)
结局指标
主要结局
Change from Baseline C-peptide after the MMTT
时间窗: week 4±1, week 12±2
change in the area under the curve of C-peptide after the MMTT vs baseline
Change from Baseline C-peptide response in the MMTT
时间窗: week 4±1, week 12±2
the proportion of participants with a positive response to the MMTT defined as C-peptide at 90 min \>0.6 ng/ml.
次要结局
- Change from Baseline HbA1c(week 4±1, week 12±2)
- Adverse Events (AEs) related to the immunosuppression(week 4±1, week 12±2)
- Change from Baseline insulin requirement(week 4±1, week 12±2)
- Change from Baseline fasting C-peptide(week 4±1, week 12±2)
- Adverse Events (AEs) and Serious Adverse Events (SAEs)(week 4±1, week 12±2)
研究者
Piemonti Lorenzo
Director San Raffaele Diabetes Research Institute (SR-DRI)
Ospedale San Raffaele