Monotherapy With Rapamycin in Long-standing Type 1 Diabetes (MONORAPA)
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ClinicalTrials.gov Identifier: NCT02803892 |
Recruitment Status :
Completed
First Posted : June 17, 2016
Last Update Posted : November 4, 2020
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Condition or disease | Intervention/treatment | Phase |
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Diabetes Mellitus, Type 1 | Drug: rapamycin Drug: Vildagliptin Drug: Placebo 1 Drug: Placebo 2 | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 55 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Care Provider) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | May 2016 |
Actual Primary Completion Date : | December 2018 |
Actual Study Completion Date : | March 2019 |

Arm | Intervention/treatment |
---|---|
Placebo Comparator: 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
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Drug: Placebo 1
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 Drug: Placebo 2 Placebo 2 will be administered BID starting from day 0. After 8 weeks of treatment patients will discontinue placebo 2 |
Experimental: 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
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Drug: rapamycin
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
Other Name: Rapamune® Drug: Vildagliptin Vildagliptin will be administered at a dose of 50 mg x2/die starting from day 0.
Other Name: GALVUS |
Experimental: 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
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Drug: rapamycin
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
Other Name: Rapamune® Drug: Vildagliptin Vildagliptin will be administered at a dose of 50 mg x2/die starting from day 0.
Other Name: GALVUS |
- Change from Baseline C-peptide response in the MMTT [ Time Frame: 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.
- Change from Baseline C-peptide after the MMTT [ Time Frame: week 4±1, week 12±2 ]change in the area under the curve of C-peptide after the MMTT vs baseline
- Change from Baseline insulin requirement [ Time Frame: week 4±1, week 12±2 ]change in insulin requirement vs baseline
- Change from Baseline fasting C-peptide [ Time Frame: week 4±1, week 12±2 ]change in fasting C-peptide vs baseline
- Change from Baseline HbA1c [ Time Frame: week 4±1, week 12±2 ]change in HbA1c vs baseline
- Adverse Events (AEs) related to the immunosuppression [ Time Frame: week 4±1, week 12±2 ]the incidence and severity of Adverse Events (AEs) related to the immunosuppressive treatment
- Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: week 4±1, week 12±2 ]Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02803892
Italy | |
IRCCS San Raffaele Scientific Institute | |
Milan, Italy, 20132 |
Principal Investigator: | Lorenzo Piemonti, MD | Ospedale San Raffaele | |
Study Chair: | Emanuele Bosi, MD | Ospedale San Raffaele |
Responsible Party: | Piemonti Lorenzo, Director San Raffaele Diabetes Research Institute (SR-DRI), Ospedale San Raffaele |
ClinicalTrials.gov Identifier: | NCT02803892 |
Other Study ID Numbers: |
DRI-2/2014 MONORAPA |
First Posted: | June 17, 2016 Key Record Dates |
Last Update Posted: | November 4, 2020 |
Last Verified: | November 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Supporting Materials: |
Study Protocol |
Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases Vildagliptin Sirolimus Anti-Bacterial Agents Anti-Infective Agents |
Antibiotics, Antineoplastic Antineoplastic Agents Antifungal Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Hypoglycemic Agents Dipeptidyl-Peptidase IV Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |