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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
55
Rapamycin will be administered at an initial dose 0.2 mg/kg on day 0, followed by 0.1 mg/kg/die. The daily dose will be adjusted to the whole blood 24-hr trough to target, as tolerated, 8-10 ng/mL
Vildagliptin will be administered at a dose of 50 mg x2/die starting from day 0.
Placebo 1 will be titrated according to a random schedule alternating plausible doses of placebo. After 4 weeks of treatment patients will discontinue placebo 1
Placebo 2 will be administered BID starting from day 0. After 8 weeks of treatment patients will discontinue placebo 2
IRCCS San Raffaele Scientific Institute
Milan, Italy
Change from Baseline C-peptide response in the MMTT
the proportion of participants with a positive response to the MMTT defined as C-peptide at 90 min \>0.6 ng/ml.
Time frame: week 4±1, week 12±2
Change from Baseline C-peptide after the MMTT
change in the area under the curve of C-peptide after the MMTT vs baseline
Time frame: week 4±1, week 12±2
Change from Baseline insulin requirement
change in insulin requirement vs baseline
Time frame: week 4±1, week 12±2
Change from Baseline fasting C-peptide
change in fasting C-peptide vs baseline
Time frame: week 4±1, week 12±2
Change from Baseline HbA1c
change in HbA1c vs baseline
Time frame: week 4±1, week 12±2
Adverse Events (AEs) related to the immunosuppression
the incidence and severity of Adverse Events (AEs) related to the immunosuppressive treatment
Time frame: week 4±1, week 12±2
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: week 4±1, week 12±2
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