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Diabetes Mellitus, Type 1Phase 2MITONCT02505893

Minimal Islet Transplant at Diabetes Onset

A Phase 2 study testing Human pancreatic islet, ATG and Pegylated G-CSF in people with Diabetes Mellitus, Type 1, run by Ospedale San Raffaele at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a prospective phase 2, single-arm, mono-center pilot study. It has been designed to investigate whether giving the combination therapy consisting of minimal islet transplantation (1500 EIQ/Kg body weight), Thymoglobulin® (ATG), Rapamune® (rapamycin) and Neulasta® (pegfilgastrim) to patients with Type 1… Read more about this study

Who is it for?
Ages 18 to 45 years
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
Human pancreatic islet, ATG and Pegylated G-CSF
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteItaly
Study dates
Apr 2015to Dec 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
  • New-onset T1D (diagnosis of diabetes within 180 days prior to enrolment). Documentation of the diagnosis of T1DM (and not just insulin deficiency), including the date of diagnosis, must be obtained from the diagnosing physician.
  • Residual beta-cell function (fasting C-peptide >0.3 ng/mLwhen plasma glucose level is > 70 mg/dL and ≤ 200 mg/dL.
  • Positive for at least one of the following autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti-GAD) antibody to protein tyrosine phosphatase-like protein (anti-IA-2), zinc transporter autoantibodies; or an insulin autoantibody (IAA). Please note: A subject who is positive for IAA and negative for the other autoantibodies will not be eligible if the subject has been using insulin for a total of ≥7 days.
  • Currently requires insulin for T1DM treatment, or has required insulin therapy (for at least 7 days) for diabetes at some time between the date of diagnosis and the first dose of study drug. Note: subjects currently taking twice daily commercially available pre-mixed insulin will not be eligible.
  • MinimalHLA I A and B mismatch and at least one HLA DR match

Who cannot join

  • Body mass index (BMI) ≥ 32.0 kg/m2 or patient weight ≤50kg
  • Insulin requirement of >1.0 IU/kg/day
  • HbA1c >10%
  • Blood Pressure: SBP >160 mmHg or DBP >100 mmHg.
  • Chronic disease apart from diabetes, including type 2 diabetes
  • Moderate to severe renal impairment as per calculated creatinine clearance (CLcr) < 90 mL/min according to the Cockcroft-Gault formula (Cockcroft-Gault , 1976)
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  • Presence or history of macroalbuminuria (>300mg/g creatinine).
  • Hepatic dysfunction defined by increased ALT/AST upper limit of normal (ULN) and increased total bilirubin > 3 mg/dL [>51.3 μmol/L]
  • Pregnant or breast feeding women. Unwillingness to use effective contraceptive measures up to 4 months after the end of study drug administration (females and males)
  • 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. Positive tests are acceptable only if associated with a history of previous vaccination in the absence of any sign of active infection. Positive tests are otherwise not acceptable, even in the absence of any active infection at the time of evaluation.
  • Negative screen for Epstein-Barr Virus (EBV) by IgG determination
  • Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year prior to study enrollment
  • Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
  • Known active alcohol or substance abuse
  • Baseline Hb below the lower limits of normal at the local laboratory; lymphopenia (<1,000/µL), neutropenia (<1,500/µL), or thrombocytopenia (platelets <100,000/µL). Participants with lymphopenia are allowed if the investigator determines there is no additional risk and obtains clearance from a hematologist
  • A history of Factor V deficiency
  • Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) after transplantation (low-dose aspirin treatment is allowed) or patients with an international normalized ratio (INR) >1.5
  • Severe co-existing cardiac disease, characterized by any one of these conditions:
  • a) recent myocardial infarction (within past 6 months)
  • b) evidence of ischemia on functional cardiac exam within the last year
  • c) left ventricular ejection fraction <30%.
  • Symptomatic cholecystolithiasis.
  • Acute or chronic pancreatitis.
  • Symptomatic peptic ulcer disease.
  • Severe unremitting diarrhea, vomiting or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications
  • Hyperlipidemia despite medical therapy (fasting low-density lipoprotein [LDL] cholesterol >130 mg/dL, treated or untreated; and/or fasting triglycerides >200 mg/dL)
  • Receiving treatment for a medical condition requiring chronic use of systemic steroids, except for the use of ≥ 5 mg prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only.
  • Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment
  • Use of any investigational agents within 4 weeks of enrollment.
  • Administration of live attenuated vaccine(s) within 2 months of enrollment.
  • Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.
  • Treatment with any immunosuppressive regimen at the time of enrollment.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • IRCCS San Raffaele Scientific Institute

    Milan, 20132

Other trials in Italy

About this study

Official title: A Monocentric, Open-label Pilot Study to Assess the Safety and Efficacy of Minimal Islet Transplantation in Patients With New-onset Type 1 Diabetes

This is a prospective phase 2, single-arm, mono-center pilot study. It has been designed to investigate whether giving the combination therapy consisting of minimal islet transplantation (1500 EIQ/Kg body weight), Thymoglobulin® (ATG), Rapamune® (rapamycin) and Neulasta® (pegfilgastrim) to patients with Type 1 Diabetes (T1D) at onset is safe and secondarily, if it will preserve insulin production. It will involve 6 patients with new-onset T1D. Each patient will be involved in the study for a screening period and a post-islet transplantation study period of 52±2 weeks, to include 1 treatment cycles of 12 weeks, assessment during treatment and 5 follow-up visits scheduled at weeks 2±1 (14 days), 4±1 (month 1), 12±2 (month 3), 26±2 (month 6) and 52±2 (month 12).

Being tested
Human pancreatic islet, ATG, Pegylated G-CSF, Rapamycin
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Human pancreatic isletBiological

    One thousand and five hundred (1,500) equivalent islet for Kg of body weight, isolated from a single brain-dead donor, will be infused into the patient's liver.

  • ATGDrug

    ATG will be administered IV (central vein) at a total dose of 6 mg/kg up to day 6 post-transplant

  • Pegylated G-CSFDrug

    Pegylated G-CSF (6 mg/dose) will be administered SC every 2 weeks for 6 doses (12 weeks) beginning after the last ATG infusion

  • RapamycinDrug

    Rapamycin will be administered orally at a starting dose of 0.2 mg/kg once a day, then targeted to blood trough level of 8-10 ng/mL and suspended one month after transplant.

Study groups in NCT02505893
Study groupRoleWhat they receive
TreatedExperimentalThe investigational treatment will be islet transplant in the presence of induction with ATG/G-CSF and rapamycin treatment for one month. One thousand and five hundred (1,500) equivalent islet for Kg of body weight, isolated from a single brain-dead donor, will be infused into the patient's liver. ATG will be administered IV (central vein) at a total dose of 6 mg/kg up to day 6 post-transplant. Pegylated G-CSF (6 mg/dose) will be administered SC every 2 weeks for 6 doses (12 weeks) beginning after the last ATG infusion. Rapamycin will be administered orally at a starting dose of 0.2 mg/kg once a day, then targeted to blood trough level of 8-10 ng/mL and suspended one month after transplant.
Receives: Biological: Human pancreatic islet; Drug: ATG; Drug: Pegylated G-CSF; Drug: Rapamycin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. plasma C-peptide AUC (mixed meal tolerance test [MMTT])

    Mean change from baseline of stimulated plasma C-peptide AUC (mixed meal tolerance test [MMTT])

    Measured: 52 weeks

  2. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: 52 weeks

Secondary outcomes (7)

  1. plasma C-peptide AUC (MMTT)

    Mean change from baseline in stimulated plasma C-peptide AUC (MMTT) at week 4, 12, 26 and month 18, 24, 36, 48, 60

    Measured: 4,12, 26 weeks and 18, 24, 36, 48, 60 months

  2. stimulated plasma C-peptide

    Maximum stimulated plasma C-peptide (the highest value at any time point during the MMTT after the mixed meal injection) at baseline, week 4, week 12, week 26 and week 52 and month 18, 24, 36, 48, 60

    Measured: 4,12, 26 weeks and 12, 18, 24, 36, 48, 60 months

  3. glucagon AUC (MMTT)

    Mean change from baseline in glucagon AUC (MMTT) at week 4, week 12, week 26 and week 52

    Measured: 4,12, 26, 52 weeks

  4. HbA1c

    Change from baseline in HbA1c at week 52 and HbA1c over time

    Measured: 4,12, 26 weeks and 12, 18, 24, 36, 48, 60 months

  5. daily insulin dose

    Change from baseline in mean daily insulin dose for the 3 days preceding the visit at weeks 4, 12, 26, 52 and month 18, 24, 36, 48, 60. The mean daily insulin dose value will be calculated, in units of U/kg/day, as the mean of the values of amount of insulin used per day on each of the 3 consecutive days.

    Measured: 4,12, 26 weeks and 12, 18, 24, 36, 48, 60 months

  6. hypoglycaemic events

    Number of hypoglycaemic events with confirmed self plasma glucose monitoring <3.1 mmol/L (<56 mg/dL) and/or requiring 3rd party intervention (i.e., severe, documented symptomatic and asymptomatic hypoglycaemic events) overall and in 3 monthly intervals

    Measured: 4,12, 26 weeks and 12, 18, 24, 36, 48, 60 months

  7. 72-hour Continuous Glucose Monitoring

    Time spent with a plasma glucose <3.9 mmol/L, between 3.9 and 10.0 mmol/L, and >10.0 mmol/L, respectively as performed by 72-hour CGM at baseline, week 26, week 52 and month 24, 36, 48, 60

    Measured: 26 and 52 weeks and 24, 36, 48, 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2015 (estimated)
  2. Study startApr 2015
  3. Primary completionMay 2018
  4. Study completionDec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02505893
Sponsor's protocol ID
DRI-MITO 1/2014
Acronym
MITO
Status last verified
Feb 2024
First submitted
21 Jul 2015
Last updated
22 Feb 2024
Results posted
No

Publications

  • Piemonti L, Bolla AM, Caretto A, Melzi R, Mercalli A, Sordi V, Monti P, Magistretti P, Lampasona V, Marzinotto I, Maffi P, Ramondetta M, Cagni N, Pedone E, Catarinella D, Cardillo M, Caldara R, Bosi E. Induction of immune education in type 1 diabetes through controlled allogeneic islet rejection at onset: a monocentric open-label pilot study. EClinicalMedicine. 2025 Dec 4;90:103685. doi: 10.1016/j.eclinm.2025.103685. eCollection 2025 Dec.

    PubMed 41438972

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Human pancreatic islet, ATG and Pegylated G-CSF in people with Diabetes Mellitus, Type 1, run by Ospedale San Raffaele at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

plasma C-peptide AUC (mixed meal tolerance test [MMTT]) (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02505893, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024; AzTrials last refreshed its copy on 6 Nov 2026.

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