Skip to main content
OpenTrials
Completed

NCT Number: NCT02803892

Monotherapy With Rapamycin in Long-standing Type 1 Diabetes

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).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Diabetes Mellitus, Type 1 Autoimmune Diseases Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

IRCCS San Raffaele Scientific Institute

Milan, 20132, Italy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Rapamycin

Drug

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 names: Rapamune®

Vildagliptin

Drug

Vildagliptin will be administered at a dose of 50 mg x2/die starting from day 0.

Other names: GALVUS

Placebo 1

Drug

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

Drug

Placebo 2 will be administered BID starting from day 0. After 8 weeks of treatment patients will discontinue placebo 2

Primary outcomes

  1. 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.

  2. 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

Secondary outcomes

  1. Change from Baseline insulin requirement

    Time frame: week 4±1, week 12±2

    change in insulin requirement vs baseline

  2. Change from Baseline fasting C-peptide

    Time frame: week 4±1, week 12±2

    change in fasting C-peptide vs baseline

  3. Change from Baseline HbA1c

    Time frame: week 4±1, week 12±2

    change in HbA1c vs baseline

  4. 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

  5. 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)

Sponsors and collaborators

Lead sponsor

Piemonti Lorenzo

Other

Collaborators

  • Italian Diabetes Foundation

Registry information

Official study 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

Acronym: MONORAPA

Important dates

Study start
2016
Primary completion
2018
Study completion
2019
First posted
Jun 17, 2016
Registry last updated
Nov 4, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.